Molecular dynamics and MM/GBSA-integrated protocol probing the correlation between biological activities and binding free energies of HIV-1 TAR RNA inhibitors.

PubMed

Peddi, Saikiran Reddy; Sivan, Sree Kanth; Manga, Vijjulatha

2018-02-01

The interaction of HIV-1 transactivator protein Tat with its cognate transactivation response (TAR) RNA has emerged as a promising target for developing antiviral compounds and treating HIV infection, since it is a crucial step for efficient transcription and replication. In the present study, molecular dynamics (MD) simulations and MM/GBSA calculations have been performed on a series of neamine derivatives in order to estimate appropriate MD simulation time for acceptable correlation between ΔG bind and experimental pIC 50 values. Initially, all inhibitors were docked into the active site of HIV-1 TAR RNA. Later to explore various conformations and examine the docking results, MD simulations were carried out. Finally, binding free energies were calculated using MM/GBSA method and were correlated with experimental pIC 50 values at different time scales (0-1 to 0-10 ns). From this study, it is clear that in case of neamine derivatives as simulation time increased the correlation between binding free energy and experimental pIC 50 values increased correspondingly. Therefore, the binding energies which can be interpreted at longer simulation times can be used to predict the bioactivity of new neamine derivatives. Moreover, in this work, we have identified some plausible critical nucleotide interactions with neamine derivatives that are responsible for potent inhibitory activity. Furthermore, we also provide some insights into a new class of oxadiazole-based back bone cyclic peptides designed by incorporating the structural features of neamine derivatives. On the whole, this approach can provide a valuable guidance for designing new potent inhibitors and modify the existing compounds targeting HIV-1 TAR RNA.

Effects of human chromosome 12 on interactions between Tat and TAR of human immunodeficiency virus type 1.

PubMed Central

Alonso, A; Cujec, T P; Peterlin, B M

1994-01-01

Rates of transcriptions of the human immunodeficiency virus are greatly increased by the viral trans activator Tat. In vitro, Tat binds to the 5' bulge of the trans-activation response (TAR) RNA stem-loop, which is present in all viral transcripts. In human cells, the central loop in TAR and its cellular RNA-binding proteins are also critical for the function of Tat. Previously, we demonstrated that in rodent cells (CHO cells), but not in those which contain the human chromosome 12 (CHO12 cells), Tat-TAR interactions are compromised. In this study, we examined the roles of the bulge and loop in TAR in Tat trans activation in these cells. Whereas low levels of trans activation depended solely on interactions between Tat and the bulge in CHO cells, high levels of trans activation depended also on interactions between Tat and the loop in CHO12 cells. Since the TAR loop binding proteins in these two cell lines were identical and different from their human counterpart, the human chromosome 12 does not encode TAR loop binding proteins. In vivo binding competition studies with TAR decoys confirmed that the binding of Tat to TAR is more efficient in CHO12 cells. Thus, the protein(s) encoded on human chromosome 12 helps to tether Tat to TAR via its loop, which results in high levels of trans activation. Images PMID:8083988

Design-Based Peptidomimetic Ligand Discovery to Target HIV TAR RNA Using Comparative Analysis of Different Docking Methods.

PubMed

Fu, Junjie; Xia, Amy; Dai, Yao; Qi, Xin

2016-01-01

Discovering molecules capable of binding to HIV trans-activation responsive region (TAR) RNA thereby disrupting its interaction with Tat protein is an attractive strategy for developing novel antiviral drugs. Computational docking is considered as a useful tool for predicting binding affinity and conducting virtual screening. Although great progress in predicting protein-ligand interactions has been achieved in the past few decades, modeling RNA-ligand interactions is still largely unexplored due to the highly flexible nature of RNA. In this work, we performed molecular docking study with HIV TAR RNA using previously identified cyclic peptide L22 and its analogues with varying affinities toward HIV-1 TAR RNA. Furthermore, sarcosine scan was conducted to generate derivatives of CGP64222, a peptide-peptoid hybrid with inhibitory activity on Tat/TAR RNA interaction. Each compound was docked using CDOCKER, Surflex-Dock and FlexiDock to compare the effectiveness of each method. It was found that FlexiDock energy values correlated well with the experimental Kd values and could be used to predict the affinity of the ligands toward HIV-1 TAR RNA with a superior accuracy. Our results based on comparative analysis of different docking methods in RNA-ligand modeling will facilitate the structure-based discovery of HIV TAR RNA ligands for antiviral therapy.

Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones

PubMed Central

Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

2013-01-01

RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous ‘polyamide amino acids’ (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy–entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets. PMID:23605042

Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones.

PubMed

Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

2013-06-01

RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous 'polyamide amino acids' (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy-entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets.

HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs

PubMed Central

Daniels, Sylvanne M; Sinck, Lucile; Ward, Natalie J; Melendez-Peña, Carlos E; Scarborough, Robert J; Azar, Ibrahim; Rance, Elodie; Daher, Aïcha; Pang, Ka-Ming; Rossi, John J; Gatignol, Anne

2015-01-01

Several proteins and RNAs expressed by mammalian viruses have been reported to interfere with RNA interference (RNAi) activity. We investigated the ability of the HIV-1-encoded RNA elements Trans-Activation Response (TAR) and Rev-Response Element (RRE) to alter RNAi. MicroRNA let7-based assays showed that RRE is a potent suppressor of RNAi activity, while TAR displayed moderate RNAi suppression. We demonstrate that RRE binds to TAR-RNA Binding Protein (TRBP), an essential component of the RNA Induced Silencing Complex (RISC). The binding of TAR and RRE to TRBP displaces small interfering (si)RNAs from binding to TRBP. Several stem-deleted RRE mutants lost their ability to suppress RNAi activity, which correlated with a reduced ability to compete with siRNA-TRBP binding. A lentiviral vector expressing TAR and RRE restricted RNAi, but RNAi was restored when Rev or GagPol were coexpressed. Adenoviruses are restricted by RNAi and encode their own suppressors of RNAi, the Virus-Associated (VA) RNA elements. RRE enhanced the replication of wild-type and VA-deficient adenovirus. Our work describes RRE as a novel suppressor of RNAi that acts by competing with siRNAs rather than by disrupting the RISC. This function is masked in lentiviral vectors co-expressed with viral proteins and thus will not affect their use in gene therapy. The potent RNAi suppressive effects of RRE identified in this study could be used to enhance the expression of RNAi restricted viruses used in oncolysis such as adenoviruses. PMID:25668122

HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs.

PubMed

Daniels, Sylvanne M; Sinck, Lucile; Ward, Natalie J; Melendez-Peña, Carlos E; Scarborough, Robert J; Azar, Ibrahim; Rance, Elodie; Daher, Aïcha; Pang, Ka-Ming; Rossi, John J; Gatignol, Anne

2015-01-01

Several proteins and RNAs expressed by mammalian viruses have been reported to interfere with RNA interference (RNAi) activity. We investigated the ability of the HIV-1-encoded RNA elements Trans-Activation Response (TAR) and Rev-Response Element (RRE) to alter RNAi. MicroRNA let7-based assays showed that RRE is a potent suppressor of RNAi activity, while TAR displayed moderate RNAi suppression. We demonstrate that RRE binds to TAR-RNA Binding Protein (TRBP), an essential component of the RNA Induced Silencing Complex (RISC). The binding of TAR and RRE to TRBP displaces small interfering (si)RNAs from binding to TRBP. Several stem-deleted RRE mutants lost their ability to suppress RNAi activity, which correlated with a reduced ability to compete with siRNA-TRBP binding. A lentiviral vector expressing TAR and RRE restricted RNAi, but RNAi was restored when Rev or GagPol were coexpressed. Adenoviruses are restricted by RNAi and encode their own suppressors of RNAi, the Virus-Associated (VA) RNA elements. RRE enhanced the replication of wild-type and VA-deficient adenovirus. Our work describes RRE as a novel suppressor of RNAi that acts by competing with siRNAs rather than by disrupting the RISC. This function is masked in lentiviral vectors co-expressed with viral proteins and thus will not affect their use in gene therapy. The potent RNAi suppressive effects of RRE identified in this study could be used to enhance the expression of RNAi restricted viruses used in oncolysis such as adenoviruses.

Structural determinants of HIV-1 nucleocapsid protein for cTAR DNA binding and destabilization, and correlation with inhibition of self-primed DNA synthesis.

PubMed

Beltz, Hervé; Clauss, Céline; Piémont, Etienne; Ficheux, Damien; Gorelick, Robert J; Roques, Bernard; Gabus, Caroline; Darlix, Jean-Luc; de Rocquigny, Hugues; Mély, Yves

2005-05-20

The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is formed of two highly conserved CCHC zinc fingers flanked by small basic domains. NC is required for the two obligatory strand transfers in viral DNA synthesis through its nucleic acid chaperoning properties. The first DNA strand transfer relies on NC's ability to bind and destabilize the secondary structure of complementary transactivation response region (cTAR) DNA, to inhibit self-priming, and to promote the annealing of cTAR to TAR RNA. To further investigate NC chaperone properties, our aim was to identify by fluorescence spectroscopy and gel electrophoresis, the NC structural determinants for cTAR binding and destabilization, and for the inhibition of self-primed DNA synthesis on a model system using a series of NC mutants and HIV-1 reverse transcriptase. NC destabilization and self-priming inhibition properties were found to be supported by the two fingers in their proper context and the basic (29)RAPRKKG(35) linker. The strict requirement of the native proximal finger suggests that its hydrophobic platform (Val13, Phe16, Thr24 and Ala25) is crucial for binding, destabilization and inhibition of self-priming. In contrast, only partial folding of the distal finger is required, probably for presenting the Trp37 residue in an appropriate orientation. Also, Trp37 and the hydrophobic residues of the proximal finger appear to be essential for the propagation of the melting from the cTAR ends up to the middle of the stem. Finally, both N-terminal and C-terminal basic domains contribute to cTAR binding but not to its destabilization.

Intrinsic Nucleic Acid Dynamics Modulates HIV-1 Nucleocapsid Protein Binding to Its Targets

PubMed Central

Bazzi, Ali; Zargarian, Loussiné; Chaminade, Françoise; De Rocquigny, Hugues; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

2012-01-01

HIV-1 nucleocapsid protein (NC) is involved in the rearrangement of nucleic acids occurring in key steps of reverse transcription. The protein, through its two zinc fingers, interacts preferentially with unpaired guanines in single-stranded sequences. In mini-cTAR stem-loop, which corresponds to the top half of the cDNA copy of the transactivation response element of the HIV-1 genome, NC was found to exhibit a clear preference for the TGG sequence at the bottom of mini-cTAR stem. To further understand how this site was selected among several potential binding sites containing unpaired guanines, we probed the intrinsic dynamics of mini-cTAR using 13C relaxation measurements. Results of spin relaxation time measurements have been analyzed using the model-free formalism and completed by dispersion relaxation measurements. Our data indicate that the preferentially recognized guanine in the lower part of the stem is exempt of conformational exchange and highly mobile. In contrast, the unrecognized unpaired guanines of mini-cTAR are involved in conformational exchange, probably related to transient base-pairs. These findings support the notion that NC preferentially recognizes unpaired guanines exhibiting a high degree of mobility. The ability of NC to discriminate between close sequences through their dynamic properties contributes to understanding how NC recognizes specific sites within the HIV genome. PMID:22745685

Critical chemical features in trans-acting-responsive RNA are required for interaction with human immunodeficiency virus type 1 Tat protein.

PubMed Central

Sumner-Smith, M; Roy, S; Barnett, R; Reid, L S; Kuperman, R; Delling, U; Sonenberg, N

1991-01-01

The human immunodeficiency virus type 1 Tat protein binds to an RNA stem-loop structure called TAR which is present at the 5' end of all human immunodeficiency virus type 1 transcripts. This binding is centered on a bulge within the stem of TAR and is an essential step in the trans-activation process which results in a dramatic increase in viral gene expression. By analysis of a series of TAR derivatives produced by transcription or direct chemical synthesis, we determined the structural and chemical requirements for Tat binding. Tat binds well to structures which have a bulge of two to at least five unpaired bases bounded on both sides by a double-stranded RNA stem. This apparent flexibility in bulge size is in contrast to an absolute requirement for an unpaired uridine (U) in the 5'-most position of the bulge (+23). Substitution of the U with either natural bases or chemical analogs demonstrated that the imido group at the N-3 position and, possibly, the carbonyl group at the C-4 position of U are critical for Tat binding. Cytosine (C), which differs from U at only these positions, is not an acceptable substitute. Furthermore, methylation at N-3 abolishes binding. While methylation of U at the C-5 position has little effect on binding, fluorination reduces it, possibly because of its effects on relative tautomer stability at the N-3 and C-4 positions. Thus, we have identified key moieties in the U residue that are of importance for the binding of Tat to TAR RNA. We hypothesize that the invariant U is involved in hydrogen bond interactions with either another part of TAR or the TAR-binding domain in Tat. Images PMID:1895380

Probing Na+ Induced Changes in the HIV-1 TAR Conformational Dynamics using NMR Residual Dipolar Couplings: New Insights into the Role of Counterions and Electrostatic Interactions in Adaptive Recognition†

PubMed Central

Casiano-Negroni, Anette; Sun, Xiaoyan; Al-Hashimi, Hashim M.

2012-01-01

Many regulatory RNAs undergo large changes in structure upon recognition of proteins and ligands but the mechanism by which this occur remains poorly understood. Using NMR residual dipolar coupling (RDCs), we characterized Na+ induced changes in the structure and dynamics of the bulge-containing HIV-1 transactivation response element (TAR) RNA that mirror changes induced by small molecules bearing a different number of cationic groups. Increasing the Na+ concentration from 25 mM to 320 mM led to a continuous reduction in the average inter-helical bend angle (from 46° to 22°), inter-helical twist angle (from 66° to −18°) and inter-helix flexibility (as measured by an increase in the internal generalized degree of order from 0.56 to 0.74). Similar conformational changes were observed with Mg2+, indicating that non-specific electrostatic interactions drive the conformational transition, although results also suggest that Na+ and Mg2+ may associate with TAR in distinct modes. The transition can be rationalized based on a population-weighted average of two ensembles comprising an electrostatically relaxed bent and flexible TAR conformation that is weakly associated with counterions, and a globally rigid coaxial conformation which has stronger electrostatic potential and association with counterions. The TAR inter-helical orientations that are stabilized by small molecules fall around the metal-induced conformational pathway, indicating that counterions may help predispose the TAR conformation for target recognition. Our results underscore the intricate sensitivity of RNA conformational dynamics to environmental conditions and demonstrate the ability to detect subtle conformational changes using NMR RDCs. PMID:17488097

Shortening the HIV-1 TAR RNA Bulge by a Single Nucleotide Preserves Motional Modes over a Broad Range of Time Scales.

PubMed

Merriman, Dawn K; Xue, Yi; Yang, Shan; Kimsey, Isaac J; Shakya, Anisha; Clay, Mary; Al-Hashimi, Hashim M

2016-08-16

Helix-junction-helix (HJH) motifs are flexible building blocks of RNA architecture that help define the orientation and dynamics of helical domains. They are also frequently involved in adaptive recognition of proteins and small molecules and in the formation of tertiary contacts. Here, we use a battery of nuclear magnetic resonance techniques to examine how deleting a single bulge residue (C24) from the human immunodeficiency virus type 1 (HIV-1) transactivation response element (TAR) trinucleotide bulge (U23-C24-U25) affects dynamics over a broad range of time scales. Shortening the bulge has an effect on picosecond-to-nanosecond interhelical and local bulge dynamics similar to that casued by increasing the Mg(2+) and Na(+) concentration, whereby a preexisting two-state equilibrium in TAR is shifted away from a bent flexible conformation toward a coaxial conformation, in which all three bulge residues are flipped out and flexible. Surprisingly, the point deletion minimally affects microsecond-to-millisecond conformational exchange directed toward two low-populated and short-lived excited conformational states that form through reshuffling of bases pairs throughout TAR. The mutant does, however, adopt a slightly different excited conformational state on the millisecond time scale, in which U23 is intrahelical, mimicking the expected conformation of residue C24 in the excited conformational state of wild-type TAR. Thus, minor changes in HJH topology preserve motional modes in RNA occurring over the picosecond-to-millisecond time scales but alter the relative populations of the sampled states or cause subtle changes in their conformational features.

Nanotherapeutics Using an HIV-1 Poly A and Transactivator of the HIV-1 LTR-(TAR-) Specific siRNA

PubMed Central

Mahajan, Supriya D.; Aalinkeel, Ravikumar; Reynolds, Jessica L.; Nair, Bindukumar; Sykes, Donald E.; Law, Wing-Cheung; Ding, Hong; Bergey, Earl J.; Prasad, Paras N.; Schwartz, Stanley A.

2011-01-01

HIV-1 replication can be efficiently inhibited by intracellular expression of an siRNA targeting the viral RNA. We used a well-validated siRNA (si510) which targets the poly A/TAR (transactivator of the HIV-1 LTR) site and suppresses viral replication. Nanotechnology holds much potential for impact in the field of HIV-1 therapeutics, and nanoparticles such as quantum rods (QRs) can be easily functionalized to incorporate siRNA forming stable nanoplexes that can be used for gene silencing. We evaluated the efficacy of the QR-si510 HIV-1 siRNA nanoplex in suppressing viral replication in the HIV-1-infected monocytic cell line THP-1 by measuring p24 antigen levels and gene expression levels of HIV-1 LTR. Our results suggest that the QR-si510 HIV-1 siRNA nanoplex is not only effective in delivering siRNA, but also in suppressing HIV-1 viral replication for a longer time period. HIV-1 nanotherapeutics can thus enhance systemic bioavailability and offer multifunctionality. PMID:21660279

Electrical detection of the biological interaction of a charged peptide via gallium arsenide junction-field-effect transistors

PubMed Central

Lee, Kangho; Nair, Pradeep R.; Alam, Muhammad A.; Janes, David B.; Wampler, Heeyeon P.; Zemlyanov, Dmitry Y.; Ivanisevic, Albena

2008-01-01

GaAs junction-field-effect transistors (JFETs) are utilized to achieve label-free detection of biological interaction between a probe transactivating transcriptional activator (TAT) peptide and the target trans-activation-responsive (TAR) RNA. The TAT peptide is a short sequence derived from the human immunodeficiency virus-type 1 TAT protein. The GaAs JFETs are modified with a mixed adlayer of 1-octadecanethiol (ODT) and TAT peptide, with the ODT passivating the GaAs surface from polar ions in physiological solutions and the TAT peptide providing selective binding sites for TAR RNA. The devices modified with the mixed adlayer exhibit a negative pinch-off voltage (VP) shift, which is attributed to the fixed positive charges from the arginine-rich regions in the TAT peptide. Immersing the modified devices into a TAR RNA solution results in a large positive VP shift (>1 V) and a steeper subthreshold slope (∼80 mV∕decade), whereas “dummy” RNA induced a small positive VP shift (∼0.3 V) without a significant change in subthreshold slopes (∼330 mV∕decade). The observed modulation of device characteristics is analyzed with analytical modeling and two-dimensional numerical device simulations to investigate the electronic interactions between the GaAs JFETs and biological molecules. PMID:19484151

Novel mechanism and factor for regulation by HIV-1 Tat.

PubMed Central

Zhou, Q; Sharp, P A

1995-01-01

Tat regulation of human immunodeficiency virus (HIV) transcription is unique because of its specificity for an RNA target, TAR, and its ability to increase the efficiency of elongation by polymerase. A reconstituted reaction that is Tat-specific and TAR-dependent for activation of HIV transcription has been used to identify and partially purify a cellular activity that is required for trans-activation by Tat, but not by other activators. In the reaction, Tat stimulates the efficiency of elongation by polymerase, whereas Sp1 and other DNA sequence-specific transcription factors activate the rate of initiation. Furthermore, while TATA binding protein (TBP)-associated factors (TAFs) in the TFIID complex are required for activation by transcription factors, they are dispensable for Tat function. Thus, Tat acts through a novel mechanism, which is mediated by a specific host cellular factor, to stimulate HIV-1 gene expression. Images PMID:7835343

Exosomes from uninfected cells activate transcription of latent HIV-1.

PubMed

Barclay, Robert A; Schwab, Angela; DeMarino, Catherine; Akpamagbo, Yao; Lepene, Benjamin; Kassaye, Seble; Iordanskiy, Sergey; Kashanchi, Fatah

2017-07-14

HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells. We observed that irrespective of combination antiretroviral therapy, both short- and long-length viral transcripts were increased in wild-type HIV-1-infected cells exposed to purified exosomes from uninfected cells. A search for a possible mechanism for this finding revealed that the exosomes increase RNA polymerase II loading onto the HIV-1 promoter in the infected cells. These viral transcripts, which include trans-activation response (TAR) RNA and a novel RNA that we termed TAR- gag , can then be packaged into exosomes and potentially be exported to neighboring uninfected cells, leading to increased cellular activation. To better decipher the exosome release pathways involved, we used siRNA to suppress expression of ESCRT (endosomal sorting complex required for transport) proteins and found that ESCRT II and IV significantly control exosome release. Collectively, these results imply that exosomes from uninfected cells activate latent HIV-1 in infected cells and that true transcriptional latency may not be possible in vivo , especially in the presence of combination antiretroviral therapy.

Activation of HIV Transcription by the Viral Tat Protein Requires a Demethylation Step Mediated by Lysine-specific Demethylase 1 (LSD1/KDM1)

PubMed Central

Sakane, Naoki; Kwon, Hye-Sook; Pagans, Sara; Kaehlcke, Katrin; Mizusawa, Yasuhiro; Kamada, Masafumi; Lassen, Kara G.; Chan, Jonathan; Greene, Warner C.; Schnoelzer, Martina; Ott, Melanie

2011-01-01

The essential transactivator function of the HIV Tat protein is regulated by multiple posttranslational modifications. Although individual modifications are well characterized, their crosstalk and dynamics of occurrence during the HIV transcription cycle remain unclear. We examine interactions between two critical modifications within the RNA-binding domain of Tat: monomethylation of lysine 51 (K51) mediated by Set7/9/KMT7, an early event in the Tat transactivation cycle that strengthens the interaction of Tat with TAR RNA, and acetylation of lysine 50 (K50) mediated by p300/KAT3B, a later process that dissociates the complex formed by Tat, TAR RNA and the cyclin T1 subunit of the positive transcription elongation factor b (P-TEFb). We find K51 monomethylation inhibited in synthetic Tat peptides carrying an acetyl group at K50 while acetylation can occur in methylated peptides, albeit at a reduced rate. To examine whether Tat is subject to sequential monomethylation and acetylation in cells, we performed mass spectrometry on immunoprecipitated Tat proteins and generated new modification-specific Tat antibodies against monomethylated/acetylated Tat. No bimodified Tat protein was detected in cells pointing to a demethylation step during the Tat transactivation cycle. We identify lysine-specific demethylase 1 (LSD1/KDM1) as a Tat K51-specific demethylase, which is required for the activation of HIV transcription in latently infected T cells. LSD1/KDM1 and its cofactor CoREST associates with the HIV promoter in vivo and activate Tat transcriptional activity in a K51-dependent manner. In addition, small hairpin RNAs directed against LSD1/KDM1 or inhibition of its activity with the monoamine oxidase inhibitor phenelzine suppresses the activation of HIV transcription in latently infected T cells. Our data support the model that a LSD1/KDM1/CoREST complex, normally known as a transcriptional suppressor, acts as a novel activator of HIV transcription through demethylation of K51 in Tat. Small molecule inhibitors of LSD1/KDM1 show therapeutic promise by enforcing HIV latency in infected T cells. PMID:21876670

NLRC5: a key regulator of MHC class I-dependent immune responses.

PubMed

Kobayashi, Koichi S; van den Elsen, Peter J

2012-12-01

The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

A Simple and Rapid Method for Standard Preparation of Gas Phase Extract of Cigarette Smoke

PubMed Central

Higashi, Tsunehito; Mai, Yosuke; Noya, Yoichi; Horinouchi, Takahiro; Terada, Koji; Hoshi, Akimasa; Nepal, Prabha; Harada, Takuya; Horiguchi, Mika; Hatate, Chizuru; Kuge, Yuji; Miwa, Soichi

2014-01-01

Cigarette smoke consists of tar and gas phase: the latter is toxicologically important because it can pass through lung alveolar epithelium to enter the circulation. Here we attempt to establish a standard method for preparation of gas phase extract of cigarette smoke (CSE). CSE was prepared by continuously sucking cigarette smoke through a Cambridge filter to remove tar, followed by bubbling it into phosphate-buffered saline (PBS). An increase in dry weight of the filter was defined as tar weight. Characteristically, concentrations of CSEs were represented as virtual tar concentrations, assuming that tar on the filter was dissolved in PBS. CSEs prepared from smaller numbers of cigarettes (original tar concentrations ≤15 mg/ml) showed similar concentration-response curves for cytotoxicity versus virtual tar concentrations, but with CSEs from larger numbers (tar ≥20 mg/ml), the curves were shifted rightward. Accordingly, the cytotoxic activity was detected in PBS of the second reservoir downstream of the first one with larger numbers of cigarettes. CSEs prepared from various cigarette brands showed comparable concentration-response curves for cytotoxicity. Two types of CSEs prepared by continuous and puff smoking protocols were similar regarding concentration-response curves for cytotoxicity, pharmacology of their cytotoxicity, and concentrations of cytotoxic compounds. These data show that concentrations of CSEs expressed by virtual tar concentrations can be a reference value to normalize their cytotoxicity, irrespective of numbers of combusted cigarettes, cigarette brands and smoking protocols, if original tar concentrations are ≤15 mg/ml. PMID:25229830

The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non-coding RNAs.

PubMed

Sunita, S; Schwartz, Samantha L; Conn, Graeme L

2015-11-20

Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an important component of the innate immune system that presents a crucial first line of defense against viral infection. PKR has a modular architecture comprising a regulatory N-terminal dsRNA binding domain and a C-terminal kinase domain interposed by an unstructured ∼80-residue interdomain linker (IDL). Guided by sequence alignment, we created IDL deletions in human PKR (hPKR) and regulatory/kinase domain swap human-rat chimeric PKRs to assess the contributions of each domain and the IDL to regulation of the kinase activity by RNA. Using circular dichroism spectroscopy, limited proteolysis, kinase assays, and isothermal titration calorimetry, we show that each PKR protein is properly folded with similar domain boundaries and that each exhibits comparable polyinosinic-cytidylic (poly(rI:rC)) dsRNA activation profiles and binding affinities for adenoviral virus-associated RNA I (VA RNAI) and HIV-1 trans-activation response (TAR) RNA. From these results we conclude that the IDL of PKR is not required for RNA binding or mediating changes in protein conformation or domain interactions necessary for PKR regulation by RNA. In contrast, inhibition of rat PKR by VA RNAI and TAR RNA was found to be weaker than for hPKR by 7- and >300-fold, respectively, and each human-rat chimeric domain-swapped protein showed intermediate levels of inhibition. These findings indicate that PKR sequence or structural elements in the kinase domain, present in hPKR but absent in rat PKR, are exploited by viral non-coding RNAs to accomplish efficient inhibition of PKR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Low-tar and high-tar cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holt, P.G.; Chalmer, J.E.; Roberts, L.M.

Mice were exposed for 7 to 8 minutes on weekdays to fresh smoke from high-tar (HT) or low-tar (LT) cigarettes for varying periods of up to 36 weeks. Mice exposed to HT cigarettes exhibited more marked alterations in humoral immune responsiveness, hematological profiles, and pulmonary pathologic findings than those exposed to LT cigarettes. However, cell-mediated immune responsiveness to both bacterial and tumor-specific antigens was depressed similarly in animals exposed to HT or LT cigarettes. Furthermore, the growth rates of subcutaneously established tumors were enhanced similarly in the two groups, with respect to those in control animals.

Quantitative Analysis of NF-κB Transactivation Specificity Using a Yeast-Based Functional Assay

PubMed Central

Sharma, Vasundhara; Jordan, Jennifer J.; Ciribilli, Yari; Resnick, Michael A.; Bisio, Alessandra; Inga, Alberto

2015-01-01

The NF-κB transcription factor family plays a central role in innate immunity and inflammation processes and is frequently dysregulated in cancer. We developed an NF-κB functional assay in yeast to investigate the following issues: transactivation specificity of NF-κB proteins acting as homodimers or heterodimers; correlation between transactivation capacity and in vitro DNA binding measurements; impact of co-expressed interacting proteins or of small molecule inhibitors on NF-κB-dependent transactivation. Full-length p65 and p50 cDNAs were cloned into centromeric expression vectors under inducible GAL1 promoter in order to vary their expression levels. Since p50 lacks a transactivation domain (TAD), a chimeric construct containing the TAD derived from p65 was also generated (p50TAD) to address its binding and transactivation potential. The p50TAD and p65 had distinct transactivation specificities towards seventeen different κB response elements (κB-REs) where single nucleotide changes could greatly impact transactivation. For four κB-REs, results in yeast were predictive of transactivation potential measured in the human MCF7 cell lines treated with the NF-κB activator TNFα. Transactivation results in yeast correlated only partially with in vitro measured DNA binding affinities, suggesting that features other than strength of interaction with naked DNA affect transactivation, although factors such as chromatin context are kept constant in our isogenic yeast assay. The small molecules BAY11-7082 and ethyl-pyruvate as well as expressed IkBα protein acted as NF-κB inhibitors in yeast, more strongly towards p65. Thus, the yeast-based system can recapitulate NF-κB features found in human cells, thereby providing opportunities to address various NF-κB functions, interactions and chemical modulators. PMID:26147604

A new macrocyclic terbium(III) complex for use in RNA footprinting experiments

PubMed Central

Belousoff, Matthew J.; Ung, Phuc; Forsyth, Craig M.; Tor, Yitzhak; Spiccia, Leone; Graham, Bim

2009-01-01

Reaction of terbium triflate with a heptadentate ligand derivative of cyclen, L1 = 2-[7-ethyl-4,10-bis(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropylacetamide, produced a new synthetic ribonuclease, [Tb(L1)(OTf)(OH2)](OTf)2·MeCN (C1). X-ray crystal structure analysis indicates that the terbium(III) centre in C1 is 9-coordinate, with a capped square-antiprism geometry. Whilst the terbium(III) center is tightly bound by the L1 ligand, two of the coordination sites are occupied by labile water and triflate ligands. In water, the triflate ligand is likely to be displaced, forming [Tb(L1)(OH2)2]3+, which is able to effectively promote RNA cleavage. This complex greatly accelerates the rate of intramolecular transesterification of an activated model RNA phosphodiester, uridine-3′-p-nitrophenylphosphate (UpNP), with kobs = 5.5(1) × 10-2 s-1 at 21°C and pH 7.5, corresponding to an apparent second-order rate constant of 277(5) M-1s-1. By contrast, the analogous complex of an octadentate derivative of cyclen featuring only a single labile coordination site, [Tb(L2)(OH2)](OTf)3 (C2), where L2 = 2-[4,7,10-tris(isopropylcarbamoylmethyl)-1,4,7,10-tetraazacyclododec-1-yl]-N-isopropyl-acetamide, is inactive. [Tb(L1)(OH2)2]3+ is also capable of hydrolyzing short transcripts of the HIV-1 transactivation response (TAR) element, HIV-1 dimerization initiation site (DIS) and ribosomal A-site, as well as formyl methionine transfer RNA (tRNAfMet), albeit at a considerably slower rate than UpNP transesterification (kobs = 2.78(8) × 10-5 M-1s-1 for TAR cleavage at 37°C, pH 6.5, corresponding to an apparent second-order rate constant of 0.56(2) M-1s-1). Cleavage is concentrated at the single-stranded “bulge” regions of these RNA motifs. Exploiting this selectivity, [Tb(L1)(OH2)23+ was successfully employed in footprinting experiments, in which binding of the Tat peptide and neomycin B to the bulge region of the TAR stem-loop was confirmed. PMID:19119812

Long noncoding RNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana.

PubMed

Zhu, Qian-Hao; Stephen, Stuart; Taylor, Jennifer; Helliwell, Chris A; Wang, Ming-Bo

2014-01-01

Short noncoding RNAs have been demonstrated to play important roles in regulation of gene expression and stress responses, but the repertoire and functions of long noncoding RNAs (lncRNAs) remain largely unexplored, particularly in plants. To explore the role of lncRNAs in disease resistance, we used a strand-specific RNA-sequencing approach to identify lncRNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana. Antisense transcription was found in c. 20% of the annotated A. thaliana genes. Several noncoding natural antisense transcripts responsive to F. oxysporum infection were found in genes implicated in disease defense. While the majority of the novel transcriptionally active regions (TARs) were adjacent to annotated genes and could be an extension of the annotated transcripts, 159 novel intergenic TARs, including 20 F. oxysporum-responsive lncTARs, were identified. Ten F. oxysporum-induced lncTARs were functionally characterized using T-DNA insertion or RNA-interference knockdown lines, and five were demonstrated to be related to disease development. Promoter analysis suggests that some of the F. oxysporum-induced lncTARs are direct targets of transcription factor(s) responsive to pathogen attack. Our results demonstrated that strand-specific RNA sequencing is a powerful tool for uncovering hidden levels of transcriptome and that IncRNAs are important components of the antifungal networks in A. thaliana. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Structure of p73 DNA-binding domain tetramer modulates p73 transactivation

PubMed Central

Ethayathulla, Abdul S.; Tse, Pui-Wah; Monti, Paola; Nguyen, Sonha; Inga, Alberto; Fronza, Gilberto; Viadiu, Hector

2012-01-01

The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation. PMID:22474346

Evolution of p53 transactivation specificity through the lens of a yeast-based functional assay.

PubMed

Lion, Mattia; Raimondi, Ivan; Donati, Stefano; Jousson, Olivier; Ciribilli, Yari; Inga, Alberto

2015-01-01

Co-evolution of transcription factors (TFs) with their respective cis-regulatory network enhances functional diversity in the course of evolution. We present a new approach to investigate transactivation capacity of sequence-specific TFs in evolutionary studies. Saccharomyces cerevisiae was used as an in vivo test tube and p53 proteins derived from human and five commonly used animal models were chosen as proof of concept. p53 is a highly conserved master regulator of environmental stress responses. Previous reports indicated conserved p53 DNA binding specificity in vitro, even for evolutionary distant species. We used isogenic yeast strains where p53-dependent transactivation was measured towards chromosomally integrated p53 response elements (REs). Ten REs were chosen to sample a wide range of DNA binding affinity and transactivation capacity for human p53 and proteins were expressed at two levels using an inducible expression system. We showed that the assay is amenable to study thermo-sensitivity of frog p53, and that chimeric constructs containing an ectopic transactivation domain could be rapidly developed to enhance the activity of proteins, such as fruit fly p53, that are poorly effective in engaging the yeast transcriptional machinery. Changes in the profile of relative transactivation towards the ten REs were measured for each p53 protein and compared to the profile obtained with human p53. These results, which are largely independent from relative p53 protein levels, revealed widespread evolutionary divergence of p53 transactivation specificity, even between human and mouse p53. Fruit fly and human p53 exhibited the largest discrimination among REs while zebrafish p53 was the least selective.

Evolution of p53 Transactivation Specificity through the Lens of a Yeast-Based Functional Assay

PubMed Central

Lion, Mattia; Raimondi, Ivan; Donati, Stefano; Jousson, Olivier; Ciribilli, Yari; Inga, Alberto

2015-01-01

Co-evolution of transcription factors (TFs) with their respective cis-regulatory network enhances functional diversity in the course of evolution. We present a new approach to investigate transactivation capacity of sequence-specific TFs in evolutionary studies. Saccharomyces cerevisiae was used as an in vivo test tube and p53 proteins derived from human and five commonly used animal models were chosen as proof of concept. p53 is a highly conserved master regulator of environmental stress responses. Previous reports indicated conserved p53 DNA binding specificity in vitro, even for evolutionary distant species. We used isogenic yeast strains where p53-dependent transactivation was measured towards chromosomally integrated p53 response elements (REs). Ten REs were chosen to sample a wide range of DNA binding affinity and transactivation capacity for human p53 and proteins were expressed at two levels using an inducible expression system. We showed that the assay is amenable to study thermo-sensitivity of frog p53, and that chimeric constructs containing an ectopic transactivation domain could be rapidly developed to enhance the activity of proteins, such as fruit fly p53, that are poorly effective in engaging the yeast transcriptional machinery. Changes in the profile of relative transactivation towards the ten REs were measured for each p53 protein and compared to the profile obtained with human p53. These results, which are largely independent from relative p53 protein levels, revealed widespread evolutionary divergence of p53 transactivation specificity, even between human and mouse p53. Fruit fly and human p53 exhibited the largest discrimination among REs while zebrafish p53 was the least selective. PMID:25668429

Algal dual-specificity tyrosine phosphorylation-regulated kinase, triacylglycerol accumulation regulator1, regulates accumulation of triacylglycerol in nitrogen or sulfur deficiency.

PubMed

Kajikawa, Masataka; Sawaragi, Yuri; Shinkawa, Haruka; Yamano, Takashi; Ando, Akira; Kato, Misako; Hirono, Masafumi; Sato, Naoki; Fukuzawa, Hideya

2015-06-01

Although microalgae accumulate triacylglycerol (TAG) and starch in response to nutrient-deficient conditions, the regulatory mechanisms are poorly understood. We report here the identification and characterization of a kinase, triacylglycerol accumulation regulator1 (TAR1), that is a member of the yeast (Saccharomyces cerevisiae) Yet another kinase1 (Yak1) subfamily in the dual-specificity tyrosine phosphorylation-regulated kinase family in a green alga (Chlamydomonas reinhardtii). The kinase domain of TAR1 showed auto- and transphosphorylation activities. A TAR1-defective mutant, tar1-1, accumulated TAG to levels 0.5- and 0.1-fold of those of a wild-type strain in sulfur (S)- and nitrogen (N)-deficient conditions, respectively. In N-deficient conditions, tar1-1 showed more pronounced arrest of cell division than the wild type, had increased cell size and cell dry weight, and maintained chlorophyll and photosynthetic activity, which were not observed in S-deficient conditions. In N-deficient conditions, global changes in expression levels of N deficiency-responsive genes in N assimilation and tetrapyrrole metabolism were noted between tar1-1 and wild-type cells. These results indicated that TAR1 is a regulator of TAG accumulation in S- and N-deficient conditions, and it functions in cell growth and repression of photosynthesis in conditions of N deficiency. © 2015 American Society of Plant Biologists. All Rights Reserved.

Generation of a Tet-On Expression System to Study Transactivation Ability of Tax-2.

PubMed

Bignami, Fabio; Sozzi, Riccardo Alessio; Pilotti, Elisabetta

2017-01-01

HTLV Tax proteins (Tax-1 and Tax-2) are known to be able to transactivate several host cellular genes involved in complex molecular pathways. Here, we describe a stable and regulated high-level expression model based on Tet-On system, to study the capacity of Tax-2 to transactivate host genes. In particular, the Jurkat Tet-On cell line suitable for evaluating the ability of Tax-2 to stimulate transactivation of a specific host gene, CCL3L1 (C-C motif chemokine ligand 3 like 1 gene), was selected. Then, a plasmid expressing tax-2 gene under control of a tetracycline-response element was constructed. To avoid the production of a fusion protein between the report gene and the inserted gene, a bidirectional plasmid was designed. Maximum expression and fast response time were achieved by using nucleofection technology as transfection method. After developing an optimized protocol for efficiently transferring tax-2 gene in Jurkat Tet-On cellular model and exposing transfected cells to Dox (doxycycline, a tetracycline derivate), a kinetics of tax-2 expression through TaqMan Real-time PCR assay was determined.

Identification and functional characterization of BTas transactivator as a DNA-binding protein.

PubMed

Tan, Juan; Hao, Peng; Jia, Rui; Yang, Wei; Liu, Ruichang; Wang, Jinzhong; Xi, Zhen; Geng, Yunqi; Qiao, Wentao

2010-09-30

The genome of bovine foamy virus (BFV) encodes a transcriptional transactivator, namely BTas, that remarkably enhances gene expression by binding to the viral long-terminal repeat promoter (LTR) and internal promoter (IP). In this report, we characterized the functional domains of BFV BTas. BTas contains two major functional domains: the N-terminal DNA-binding domain (residues 1-133) and the C-terminal activation domain (residues 198-249). The complete BTas responsive regions were mapped to the positions -380/-140 of LTR and 9205/9276 of IP. Four BTas responsive elements were identified at the positions -368/-346, -327/-307, -306/-285 and -186/-165 of the BFV LTR, and one element was identified at the position 9243/9264 of the BFV IP. Unlike other foamy viruses, the five BTas responsive elements in BFV shared obvious sequence homology. These data suggest that among the complex retroviruses, BFV appears to have a unique transactivation mechanism. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

A Luciferase Functional Quantitative Assay for Measuring NF-ĸB Promoter Transactivation Mediated by HTLV-1 and HTLV-2 Tax Proteins.

PubMed

Bergamo, Elisa; Diani, Erica; Bertazzoni, Umberto; Romanelli, Maria Grazia

2017-01-01

HTLV-1 and HTLV-2 viruses express Tax transactivator proteins required for viral genome transcription and capable of transforming cells in vivo and in vitro. Although Tax oncogenic potential needs to be further elucidated, it is well established that Tax proteins activate, among others, transcription factors of the NF-ĸB family, which are involved in immune and inflammatory responses, cell growth, apoptosis, stress responses and oncogenesis. Here, we describe a reporter gene assay applied for quantitative analysis of Tax-dependent NF-ĸB activation. The procedure is based on co-transfection of two individual vectors containing the cDNA for firefly and Renilla luciferase enzymes and vectors expressing Tax proteins. The luciferase expression is driven by cis-NF-ĸB promoter regulatory elements responsive to Tax transactivating factor. This assay is particularly useful to investigate Tax influence on NF-ĸB activation mediated by viral or host factors.

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

PubMed Central

Dong, Wen; Li, Yi; Gao, Ming; Hu, Meiru; Li, Xiaoguang; Mai, Sanyue; Guo, Ning; Yuan, Shengtao; Song, Lun

2012-01-01

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. PMID:22169952

Coal-tar based pavement sealant toxicity to freshwater macroinvertebrates.

PubMed

Bryer, Pamela J; Scoggins, Mateo; McClintock, Nancy L

2010-05-01

Non-point-source pollution is a major source of ecological impairment in urban stream systems. Recent work suggests that coal-tar pavement sealants, used extensively to protect parking areas, may be contributing a large portion of the polycyclic aromatic hydrocarbon (PAH) loading seen in urban stream sediments. The hypothesis that dried coal-tar pavement sealant flake could alter the macroinvertebrate communities native to streams in Austin, TX was tested using a controlled outdoor laboratory type approach. The treatment groups were: control, low, medium, and high with total PAH concentrations (TPAH = sum of 16 EPA priority pollutant PAHs) of 0.1, 7.5, 18.4, & 300 mg/kg respectively. The low, medium, and high treatments were created via the addition of dried coal-tar pavement sealant to a sterile soil. At the start of the 24-day exposure, sediment from a minimally impacted local reference site containing a community of live sediment-dwelling benthic macroinvertebrates was added to each replicate. An exposure-dependent response was found for several stream health measures and for several individual taxa. There were community differences in abundance (P = 0.0004) and richness (P < 0.0001) between treatments in addition to specific taxa responses, displaying a clear negative relationship with the amount of coal-tar sealant flake. These results support the hypothesis that coal-tar pavement sealants contain bioavailable PAHs that may harm aquatic environments. Copyright 2009 Elsevier Ltd. All rights reserved.

A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion

PubMed Central

Legrand, Nicolas; van der Velden, Gisela J.; Fang, Raphaël Ho Tsong; Douaisi, Marc; Weijer, Kees; Das, Atze T.; Blom, Bianca; Uittenbogaart, Christel H.; Berkhout, Ben

2012-01-01

A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant, HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can be turned on and off at will in a graded and reversible manner. The in vivo replication capacity, pathogenicity and genetic stability of this HIV-rtTA variant were evaluated in a humanized mouse model of haematopoiesis that harbours lymphoid and myeloid components of the human immune system (HIS). Infection of dox-fed BALB Rag/γc HIS (BRG-HIS) mice with HIV-rtTA led to the establishment of a productive infection without CD4+ T-cell depletion. The virus did not show any sign of escape from dox control for up to 10 weeks after the onset of infection. No reversion towards a functional Tat–transactivating responsive (TAR) RNA element axis was observed, confirming the genetic stability of the HIV-rtTA variant in vivo. These results demonstrate the proof of concept that HIV-rtTA replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental research to study virus–host interactions in vivo in a controlled fashion. PMID:22647372

Recognition of Double Stranded RNA by Guanidine-Modified Peptide Nucleic Acids (GPNA)

PubMed Central

Gupta, Pankaj; Muse, Oluwatoyosi; Rozners, Eriks

2011-01-01

Double helical RNA has become an attractive target for molecular recognition because many non-coding RNAs play important roles in control of gene expression. Recently, we discovered that short peptide nucleic acids (PNA) bind strongly and sequence selectively to a homopurine tract of double helical RNA via triple helix formation. Herein we tested if the molecular recognition of RNA can be enhanced by α-guanidine modification of PNA. Our study was motivated by the discovery of Ly and co-workers that the guanidine modification greatly enhances the cellular delivery of PNA. Isothermal titration calorimetry showed that the guanidine-modified PNA (GPNA) had reduced affinity and sequence selectivity for triple helical recognition of RNA. The data suggested that in contrast to unmodified PNA, which formed a 1:1 PNA-RNA triple helix, GPNA preferred a 2:1 GPNA-RNA triplex-invasion complex. Nevertheless, promising results were obtained for recognition of biologically relevant double helical RNA. Consistent with enhanced strand invasion ability, GPNA derived from D-arginine recognized the transactivation response element (TAR) of HIV-1 with high affinity and sequence selectivity, presumably via Watson-Crick duplex formation. On the other hand, strong and sequence selective triple helices were formed by unmodified and nucelobase-modified PNAs and the purine rich strand of bacterial A-site. These results suggest that appropriate chemical modifications of PNA may enhance molecular recognition of complex non-coding RNAs. PMID:22146072

The chimeric VirA-tar receptor protein is locked into a highly responsive state.

PubMed Central

Turk, S C; van Lange, R P; Sonneveld, E; Hooykaas, P J

1993-01-01

The wild-type VirA protein is known to be responsive not only to phenolic compounds but also to sugars via the ChvE protein (G. A. Cangelosi, R. G. Ankenbauer, and E. W. Nester, Proc. Natl. Acad. Sci. USA 87:6708-6712, 1990, and N. Shimoda, A. Toyoda-Yamamoto, J. Nagamine, S. Usami, M. Katayama, Y. Sakagami, and Y. Machida, Proc. Natl. Acad. Sci. USA 87:6684-6688, 1990). It is shown here that the mutant VirA(Ser-44, Arg-45) protein and the chimeric VirA-Tar protein are no longer responsive to sugars and the ChvE protein. However, whereas the chimeric VirA-Tar protein was found to be locked in a highly responsive state, the VirA(Ser-44, Arg-45) mutant protein appeared to be locked in a low responsive state. This difference turned out to be important for tumorigenicity of the host strains in virulence assays on Kalanchoë daigremontiana. Images PMID:8366057

Functional analysis of four naturally occurring variants of human constitutive androstane receptor.

PubMed

Ikeda, Shinobu; Kurose, Kouichi; Jinno, Hideto; Sai, Kimie; Ozawa, Shogo; Hasegawa, Ryuichi; Komamura, Kazuo; Kotake, Takeshi; Morishita, Hideki; Kamakura, Shiro; Kitakaze, Masafumi; Tomoike, Hitonobu; Tamura, Tomohide; Yamamoto, Noboru; Kunitoh, Hideo; Yamada, Yasuhide; Ohe, Yuichiro; Shimada, Yasuhiro; Shirao, Kuniaki; Kubota, Kaoru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Saito, Yoshiro; Sawada, Jun-ichi

2005-01-01

The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan nuclear receptor superfamily that plays an important role in the control of drug metabolism and disposition. In this study, we sequenced all the coding exons of the NR1I3 gene for 334 Japanese subjects. We identified three novel single nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain of CAR, in addition to the Val133Gly variant, which was another CAR variant identified in our previous study. We performed functional analysis of these four naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer reporter gene that includes the CAR responsive elements. The His246Arg variant caused marked reductions in both transactivation of the reporter gene and in the response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The transactivation ability of the Leu308Pro variant was also significantly decreased, but its responsiveness to CITCO was not abrogated. The transactivation ability and CITCO response of the Val133Gly and Asn323Ser variants did not change as compared to the wild-type CAR. These data suggest that the His246Arg and Leu308Pro variants, especially His246Arg, may influence the expression of drug-metabolizing enzymes and transporters that are transactivated by CAR.

Chemotactic signal integration in bacteria.

PubMed Central

Khan, S; Spudich, J L; McCray, J A; Trentham, D R

1995-01-01

Chemotactic signaling in Escherichia coli involves transmission of both negative and positive signals. In order to examine mechanisms of signal processing, behavioral responses to dual inputs have been measured by using photoactivable "caged" compounds, computer video analysis, and chemoreceptor deletion mutants. Signaling from Tar and Tsr, two receptors that sense amino acids and pH, was studied. In a Tar deletion mutant the photoactivated release of protons, a Tsr repellent, and of serine, a Tsr attractant, in separate experiments at pH 7.0 resulted in tumbling (negative) or smooth-swimming (positive) responses in ca. 50 and 140 ms, respectively. Simultaneous photorelease of protons and serine resulted in a single tumbling or smooth-swimming response, depending on the relative amounts of the two effectors. In contrast, in wild-type E. coli, proton release at pH 7.0 resulted in a biphasic response that was attributed to Tsr-mediated tumbling followed by Tar-mediated smooth-swimming. In wild-type E. coli at more alkaline pH values the Tar-mediated signal was stronger than the Tsr signal, resulting in a strong smooth-swimming response preceded by a diminished tumbling response. These observations imply that (i) a single receptor time-averages the binding of different chemotactic ligands generating a single response; (ii) ligand binding to different receptors can result in a nonintegrated response with the tumbling response preceding the smooth-swimming response; (iii) however, chemotactic signals of different intensities derived from different receptors can also result in an apparently integrated response; and (iv) the different chemotactic responses to protons at neutral and alkaline pH may contribute to E. coli migration toward neutrality. Images Fig. 6 PMID:7568212

The viral protein A238L inhibits cyclooxygenase-2 expression through a nuclear factor of activated T cell-dependent transactivation pathway.

PubMed

Granja, Aitor G; Nogal, Maria L; Hurtado, Carolina; Vila, Virginia; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

2004-12-17

Cyclooxygenase-2 is transiently induced upon cell activation or viral infections, resulting in inflammation and modulation of the immune response. Here we report that A238L, an African swine fever virus protein, efficiently inhibits cyclooxygenase-2 gene expression in Jurkat T cells and in virus-infected Vero cells. Transfection of Jurkat cells stably expressing A238L with cyclooxygenase-2 promoter-luciferase constructs containing 5'-terminal deletions or mutations in distal or proximal nuclear factor of activated T cell (NFAT) response elements revealed that these sequences are involved in the inhibition induced by A238L. Overexpression of a constitutively active version of the calcium-dependent phosphatase calcineurin or NFAT reversed the inhibition mediated by A238L on cyclooxygenase-2 promoter activation, whereas overexpression of p65 NFkappaB had no effect. A238L does not modify the nuclear localization of NFAT after phorbol 12-myristate 13-acetate/calcium ionophore stimulation. Moreover, we show that the mechanism by which the viral protein down-regulates cyclooxygenase-2 activity does not involve inhibition of the binding between NFAT and its specific DNA sequences into the cyclooxygenase-2 promoter. Strikingly, A238L dramatically inhibited the transactivation mediated by a GAL4-NFAT fusion protein containing the N-terminal transactivation domain of NFAT1. Taken together, these data indicate that A238L down-regulates cyclooxygenase-2 transcription through the NFAT response elements, being NFAT-dependent transactivation implicated in this down-regulation.

Treatment policy for psoriasis and eczema: a survey among dermatologists in the Netherlands and Belgian Flanders.

PubMed

Roelofzen, Judith H J; Aben, Katja K H; Khawar, Ali J M; Van de Kerkhof, Peter C M; Kiemeney, Lambertus A L M; Van Der Valk, Pieter G M

2007-01-01

Today, many therapies are available for the treatment of psoriasis and eczema. One of the oldest topical therapies is coal tar. Coal tar has been used for decades, but over the past years, the use of coal tar has decreased for several reasons, including the supposed carcinogenicity of coal tar. We investigated the current and past treatment policies for psoriasis and eczema with special emphasis on the use of tar products; a postal survey was conducted among all dermatologists in two European countries: the Netherlands (n = 360) and the Flemish speaking part of Belgium (Flanders) (n = 328). This study was conducted as part of the ongoing LATER-study ("Late effects of coal tar treatment in eczema and psoriasis; the Radboud study"). All practising dermatologists received a questionnaire. Dermatologists were asked to describe their treatment policies in mild/moderate psoriasis, severe psoriasis, mild/moderate eczema and severe eczema. The response rate to the questionnaire was 62.5% for the Dutch dermatologists and 45.7% for the Flemish dermatologists. Almost all dermatologists prescribe topical corticosteroids. In eczema, most of the dermatologists prescribe the recently introduced calcineurin inhibitors (95%). Coal tar is a second choice topical therapy. Dutch dermatologists mainly use tar in the treatment of eczema (72% vs. 48% in Flanders), whereas in Flanders, tar is mainly prescribed in psoriasis (60% vs. 41% in Holland). Flemish dermatologists very frequently prescribe PUVA in psoriasis (93% vs. 63%). Topical treatment, especially topical corticosteroids, is the mainstay in psoriasis and eczema. Coal tar still is an important (second choice) therapy for the topical treatment of psoriasis and eczema, but its use varies from country to country. Despite the carcinogenicity of PUVA, this photochemotherapy is frequently prescribed by dermatologists, mainly in Flanders.

Musa spp. germplasm management: microsatellite fingerprinting of USDA-ARS National Plant Germplasm System (NPGS) collection

USDA-ARS?s Scientific Manuscript database

The USDA-ARS Tropical Agriculture Research Station (TARS) is responsible for conserving germplasm of a number of important agricultural crop species. A banana (Musa spp.) collection has been established at TARS that is comprised of diploid, triploid and tetraploid accessions of cultivated, ornament...

Effects of FSH and 17beta-estradiol on the transactivation of estrogen-regulated promoters and cell proliferation in L cells.

PubMed

Pasapera, Ana María; Jiménez-Aguilera, María del Pilar; Chauchereau, Anne; Milgrom, Edwin; Olivares, Aleida; Uribe, Aída; Gutiérrez-Sagal, Rubén; Ulloa-Aguirre, Alfredo

2005-03-01

In the present study, we analyzed human follicle-stimulating hormone (FSH)-induced cell proliferation and transactivation of estrogen-sensitive reporter genes-in L cells stably expressing the human FSH receptor [L-(hFSHR(+)) cells]. In order to dissect the signaling pathways involved in this process, L-(hFSHR(+)) cells were transiently transfected with either the 3X-ERE-TAT-Luc or the ERE-VitA2-TK-CAT reporter genes and treated with FSH or PKA activators (cholera toxin, forskolin and 8-Br-cAMP) in the presence or absence of various kinase inhibitors. We found that FSH and all PKA activators, specifically induced transactivation of both reporter genes. Transactivation of estrogen-sensitive genes by FSH or PKA activators were blocked (approximately 90%) by H89 (PKA inhibitor) and LY294002 but not by Wortmannin (PI3-K inhibitors), 4-OH-tamoxifen, ICI182,780 or SB203580 (p38 MAPK inhibitor); PD98059 (ERK1/2 inhibitor) partially (approximately 30%) blocked the FSH-mediated effect. The combination of FSH and estradiol resulted in a synergistic effect on transactivation as well as on cell proliferation, and this enhancement was attenuated by antiestrogens. We additionally analyzed the participation of the coactivators SRC-1 and cAMP response element binding protein (CREB)-binding protein (CBP) in FSH-evoked estrogen receptor (ER)-dependent transactivation; we found that CBP but not SRC-1 potentiated FSH-induced transcriptional activation of both ER-sensitive reporters, being this effect stronger on the ERE-VitA2-TK-CAT than on the 3X-ERE-TAT-Luc reporter. Thus, in L-(hFSHR(+)) cells FSH induces transcriptional activation of estrogen-sensitive genes through an A-kinase-triggered signaling pathway, using also to a lesser extent the ERK1/2 and p38 pathways. PI3-K is not apparently involved in this FSH-mediated process since LY294002, but not Wortmannin, specifically binds ERs and completely blocks estrogen action. Presumably, CBP cooperates with the ER on genes that contain estrogen responsive elements through mechanisms involving the participation of other proteins and/or basal transcription factors (e.g. CREB), which in turn mediate the transcriptional response of estrogen-sensitive reporter genes to FSH stimulation.

Activation of the canonical beta-catenin pathway by histamine.

PubMed

Diks, Sander H; Hardwick, James C; Diab, Remco M; van Santen, Marije M; Versteeg, Henri H; van Deventer, Sander J H; Richel, Dick J; Peppelenbosch, Maikel P

2003-12-26

Histamine signaling is a principal regulator in a variety of pathophysiological processes including inflammation, gastric acid secretion, neurotransmission, and tumor growth. We report that histamine stimulation causes transactivation of a T cell factor/beta-catenin-responsive construct in HeLa cells and in the SW-480 colon cell line, whereas histamine did not effect transactivation of a construct containing the mutated response construct FOP. On the protein level, histamine treatment increases phosphorylation of glycogen synthase kinase 3-beta in HeLa cells, murine macrophages, and DLD-1, HT-29, and SW-480 colon cell lines. Furthermore, histamine also decreases the phosphorylated beta-catenin content in HeLa cells and murine macrophages. Finally, pharmacological inhibitors of the histamine H1 receptor counteracted histamine-induced T cell factor/beta-catenin-responsive construct transactivation and the dephosphorylation of beta-catenin in HeLa cells and in macrophages. We conclude that the canonical beta-catenin pathway acts downstream of the histamine receptor H1 in a variety of cell types. The observation that inflammatory molecules, like histamine, activate the beta-catenin pathway may provide a molecular explanation for a possible link between inflammation and cancer.

The Australian tar derby: the origins and fate of a low tar harm reduction programme

PubMed Central

King, W; Carter, S; Borland, R; Chapman, S; Gray, N

2003-01-01

Objective: To document the development of the low tar harm reduction programme in Australia, including tobacco industry responses. Data sources: Tobacco industry documents, retail tobacco journals, newspapers, medical journals, and Anti-Cancer Council of Victoria (ACCV) newsletters and archival records. Study selection: Documents on the strategies and knowledge bases of the ACCV, other Australian health authorities, and the tobacco industry. Results: The ACCV built a durable system for measuring and publicising the tar and nicotine yields of Australian cigarettes and influencing their development. The tobacco industry initially sought to block the development of this system but later appeared to cooperate with it, as is evidenced by the current market dominance of low tar brands. However, behind the scenes, the industry used its substantial knowledge advantage regarding compensatory smoking and its ability to re-engineer cigarettes to gain effective control of the system and subvert the ACCV's objectives. Conclusions: Replacement of the low tar programme with new means of minimising the harms from cigarette smoking should be a policy priority for the Australian government. This will require regulation, rather than further voluntary agreements, and stringent monitoring of successor programmes will be necessary. PMID:14645950

The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

PubMed Central

Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

2013-01-01

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons.

PubMed

Cykowski, Matthew D; Takei, Hidehiro; Van Eldik, Linda J; Schmitt, Frederick A; Jicha, Gregory A; Powell, Suzanne Z; Nelson, Peter T

2016-05-01

Transactivating responsive sequence (TAR) DNA-binding protein 43-kDa (TDP-43) pathology has been described in various brain diseases, but the full anatomical distribution and clinical and biological implications of that pathology are incompletely characterized. Here, we describe TDP-43 neuropathology in the basal forebrain, hypothalamus, and adjacent nuclei in 98 individuals (mean age, 86 years; median final mini-mental state examination score, 27). On examination blinded to clinical and pathologic diagnoses, we identified TDP-43 pathology that most frequently involved the ventromedial basal forebrain in 19 individuals (19.4%). As expected, many of these brains had comorbid pathologies including those of Alzheimer disease (AD), Lewy body disease (LBD), and/or hippocampal sclerosis of aging (HS-Aging). The basal forebrain TDP-43 pathology was strongly associated with comorbid HS-Aging (odds ratio = 6.8, p = 0.001), whereas there was no significant association between basal forebrain TDP-43 pathology and either AD or LBD neuropathology. In this sample, there were some cases with apparent preclinical TDP-43 pathology in the basal forebrain that may indicate that this is an early affected area in HS-Aging. We conclude that TDP-43 pathology in the basal forebrain is strongly associated with HS-Aging. These results raise questions about a specific pathogenetic relationship between basal forebrain TDP-43 and non-HS-Aging comorbid diseases (AD and LBD). © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons

PubMed Central

Takei, Hidehiro; Van Eldik, Linda J.; Schmitt, Frederick A.; Jicha, Gregory A.; Powell, Suzanne Z.; Nelson, Peter T.

2016-01-01

Transactivating responsive sequence (TAR) DNA-binding protein 43-kDa (TDP-43) pathology has been described in various brain diseases, but the full anatomical distribution and clinical and biological implications of that pathology are incompletely characterized. Here, we describe TDP-43 neuropathology in the basal forebrain, hypothalamus, and adjacent nuclei in 98 individuals (mean age, 86 years; median final mini-mental state examination score, 27). On examination blinded to clinical and pathologic diagnoses, we identified TDP-43 pathology that most frequently involved the ventromedial basal forebrain in 19 individuals (19.4%). As expected, many of these brains had comorbid pathologies including those of Alzheimer disease (AD), Lewy body disease (LBD), and/or hippocampal sclerosis of aging (HS-Aging). The basal forebrain TDP-43 pathology was strongly associated with comorbid HS-Aging (odds ratio = 6.8, p = 0.001), whereas there was no significant association between basal forebrain TDP-43 pathology and either AD or LBD neuropathology. In this sample, there were some cases with apparent preclinical TDP-43 pathology in the basal forebrain that may indicate that this is an early affected area in HS-Aging. We conclude that TDP-43 pathology in the basal forebrain is strongly associated with HS-Aging. These results raise questions about a specific pathogenetic relationship between basal forebrain TDP-43 and non-HS-Aging comorbid diseases (AD and LBD). PMID:26971127

Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein.

PubMed

Alexandre, C; Verrier, B

1991-04-01

Expression of the human c-fos proto-oncogene is activated in trans by the Tax protein encoded by human T-cell leukemia virus type-1 (HTLV-1). Indeed, we show here that a HeLa clone stably transfected by Tax expresses Fos at a high level. We also show that multiple elements of the human c-fos promoter, i.e. the v-sis conditioned medium inducible element (SIE), the dyad symmetry element (DSE) necessary for growth factor induction, the octanucleotide direct repeat element (DR), and the cyclic AMP response element (CRE) centred at -60, can all mediate Tax transactivation. In the DSE, the 10bp central core that binds the serum response factor (SRF) is, by itself, sufficient to mediate Tax transactivation. Moreover, a CRE-binding protein is involved in Tax activation through the CRE-60 element. Since Fos is a transregulator of cellular genes, our results suggest that the oncoprotein plays a crucial role in T-cell transformation by HTLV-1 in conjunction with other Tax-inducible genes.

An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat.

PubMed

Kenney, S; Kamine, J; Markovitz, D; Fenrick, R; Pagano, J

1988-03-01

Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, we demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

PubMed Central

Harrod, Robert; Tang, Yong; Nicot, Christophe; Lu, Hsieng S.; Vassilev, Alex; Nakatani, Yoshihiro; Giam, Chou-Zen

1998-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) transcriptional activation is mediated by the viral transactivator, Tax, and three 21-bp repeats (Tax response element [TxRE]) located in the U3 region of the viral long terminal repeat (LTR). Each TxRE contains a core cyclic AMP response element (CRE) flanked by 5′ G-rich and 3′ C-rich sequences. The TxRE binds CREB (CRE-binding protein) and Tax to form a ternary complex and confers Tax-dependent transactivation. Recent data indicate that Tax functions as a specific link to connect CREB-binding protein (CBP)/p300 in a phosphorylation-independent manner to CREB/ATF-1 assembled on the viral 21-bp repeats. Glutathione S-transferase pull-down performed with Tax deletion mutants and peptide competition have localized the site in Tax critical for binding CBP/p300 to a highly protease-sensitive region around amino acid residues 81 to 95 (81QRTSKTLKVLTPPIT95) which lies between the domains previously proposed to be important for CREB binding and Tax subunit dimerization. Amino acid residues around the trypsin- and chymotrypsin-sensitive sites (88KVL90) of Tax bear resemblance to those in the kinase-inducible domain of CREB (129SRRPSYRKILNE140) surrounding Ser-133, which undergoes signal-induced phosphorylation to recruit CBP/p300. Site-directed mutagenesis of residues in this domain (R82A, K85A, K88A, and V89A) resulted in proteins which failed to transactivate from the HTLV-1 LTR in vivo. These mutants (K85A, K88A, and V89A) bind CREB with similar affinities as wild-type Tax, yet interaction with CBP/p300 is abrogated in various biochemical assays, indicating that the recruitment of CBP/p300 is crucial for Tax transactivation. A Tax mutant, M47, defective in the COOH-terminal transactivation domain, continued to interact with CBP/p300, suggesting that interactions with additional cellular factors are required for proper Tax function. PMID:9710589

ATF2 impairs glucocorticoid receptor–mediated transactivation in human CD8+ T cells

PubMed Central

Li, Ling-bo; Leung, Donald Y. M.; Strand, Matthew J.

2007-01-01

Chronic inflammatory diseases often have residual CD8+ T-cell infiltration despite treatment with systemic corticosteroids, which suggests divergent steroid responses between CD4+ and CD8+ cells. To examine steroid sensitivity, dexamethasone (DEX)–induced histone H4 lysine 5 (K5) acetylation and glucocorticoid receptor α (GCRα) translocation were evaluated. DEX treatment for 6 hours significantly induced histone H4 K5 acetylation in normal CD4+ cells (P = .001) but not in CD8+ cells. DEX responses were functionally impaired in CD8+ compared with CD4+ cells when using mitogen-activated protein kinase phosphatase (1 hour; P = .02) and interleukin 10 mRNA (24 hours; P = .004) induction as a readout of steroid-induced transactivation. Normal DEX-induced GCRα nuclear translocation and no significant difference in GCRα and GCRβ mRNA expression were observed in both T-cell types. In addition, no significant difference in SRC-1, p300, or TIP60 expression was found. However, activating transcription factor-2 (ATF2) expression was significantly lower in CD8+ compared with CD4+ cells (P = .009). Importantly, inhibition of ATF2 expression by small interfering RNA in CD4+ cells resulted in inhibition of DEX-induced transactivation in CD4+ cells. The data indicate refractory steroid-induced transactivation but similar steroid-induced transrepression of CD8+ cells compared with CD4+ cells caused by decreased levels of the histone acetyltransferase ATF2. PMID:17525285

Hybrid Escherichia coli sensory transducers with altered stimulus detection and signaling properties.

PubMed Central

Slocum, M K; Halden, N F; Parkinson, J S

1987-01-01

The tar and tap loci of Escherichia coli encode methyl-accepting inner membrane proteins that mediate chemotactic responses to aspartate and maltose or to dipeptides. These genes lie adjacent to each other in the same orientation on the chromosome and have extensive sequence homology throughout the C-terminal portions of their coding regions. Many spontaneous deletions in the tar-tap region appear to be generated by recombination between these regions of homology, leading to gene fusions that produce hybrid transducer molecules in which the N terminus of Tar is joined to the C terminus of Tap. The properties of two such hybrids are described in this report. Although Tar and Tap molecules have homologous domain structures, these Tar-Tap hybrids exhibited defects in stimulus detection and flagellar signaling. Both hybrid transducers retained Tar receptor specificity, but had reduced detection sensitivity. This defect was correlated with the presence of the C-terminal methyl-accepting segment of Tap, which may have more methylation sites than its Tar counterpart, leading to elevated steady-state methylation levels in the hybrid molecules. One of the hybrids, which carried a more extensive segment from Tap, appeared to generate constitutive signals that locked the flagellar motors in a counterclockwise rotational mode. Changes in the methylation state of this transducer were ineffective in cancelling this aberrant signal. These findings implicate the conserved C-terminal domain of bacterial transducers in the generation or regulation of flagellar signals. Images PMID:3110130

Detection of potential (anti)progestagenic endocrine disruptors using a recombinant human progesterone receptor binding and transactivation assay.

PubMed

Viswanath, Gunda; Halder, Sujata; Divya, Gunda; Majumder, Chandrajeet B; Roy, Partha

2008-11-25

The present work describes the identification of (anti)progestin endocrine disrupting chemicals (EDC) using a two step screening system. In the first step a competitive binding assay was developed using recombinant human progesterone receptor (hPR). The tested chemicals were of various classes like insecticides, their metabolites, industrial chemicals and waste water treatment plant (WWTP) effluents. All the tested chemicals demonstrated a high affinity binding for hPR. The average IC50 values of the test chemicals were within the range of 1-25microM. In the second step of screening, a mammalian cell-based hPR transactivation assay was developed where HEK 293 cells were co-transfected with hPR and luciferase reporter gene under the control of progesterone-response element. Stimulation of the cells with progesterone resulted in about 25-fold up regulation of luciferase activity, with EC50 value of 4nM. Potent anti-progesterone, RU486, significantly inhibited progesterone-induced transactivation and non-progestagenic steroids failed to transactivate hPR till 1microM concentrations. The chemicals showing high binding affinities in competitive binding assays were then tested in transactivation assay and all of them were found to be anti-progestative except WWTP effluents. Transactivation assays using extracted water samples from five different WWTP effluents showed that it was rich in progestative compounds. The levels of induction caused by these effluents were in the range of 15-25% of induction by progesterone and they represented about 6ng/l equivalent progesterone activities. In conclusion, we demonstrated that this two step assay provides an efficient screening tool for the detection of (anti)progestative EDC in various samples.

Transactivation of a cellular promoter by the NS1 protein of the parvovirus minute virus of mice through a putative hormone-responsive element.

PubMed Central

Vanacker, J M; Corbau, R; Adelmant, G; Perros, M; Laudet, V; Rommelaere, J

1996-01-01

The promoter of the thyroid hormone receptor alpha gene (c-erbA-1) is activated by the nonstructural protein 1 (NS1) of parvovirus minute virus of mice (prototype strain [MVMp]) in ras-transformed FREJ4 cells that are permissive for lytic MVMp replication. This stimulation may be related to the sensitivity of host cells to MVMp, as it does not take place in parental FR3T3 cells, which are resistant to the parvovirus killing effect. The analysis of a series of deletion and point mutants of the c-erbA-1 promoter led to the identification of an upstream region that is necessary for NS1-driven transactivation. This sequence harbors a putative hormone-responsive element and is sufficient to render a minimal promoter NS1 inducible in FREJ4 but not in FR3T3 cells, and it is involved in distinct interactions with proteins from the respective cell lines. The NS1-responsive element of the c-erbA-1 promoter bears no homology with sequences that were previously reported to be necessary for NS1 DNA binding and transactivation. Altogether, our data point to a novel, cell-specific mechanism of promoter activation by NS1. PMID:8642664

Curcumin differentially regulates endoplasmic reticulum stress through transcriptional corepressor SMILE (small heterodimer partner-interacting leucine zipper protein)-mediated inhibition of CREBH (cAMP responsive element-binding protein H).

PubMed

Misra, Jagannath; Chanda, Dipanjan; Kim, Don-kyu; Li, Tiangang; Koo, Seung-Hoi; Back, Sung-Hoon; Chiang, John Y L; Choi, Hueng-Sik

2011-12-09

Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), is a natural polyphenolic compound. Herein the effect of curcumin on endoplasmic reticulum (ER) stress responsive gene expression was investigated. We report that curcumin induces transcriptional corepressor small heterodimer partner-interacting leucine zipper protein (SMILE) gene expression through liver kinase B1 (LKB1)/adenosine monophosphate-activated kinase (AMPK) signaling pathway and represses ER stress-responsive gene transcription in an ER-bound transcription factor specific manner. cAMP responsive element-binding protein H (CREBH) and activating transcription factor 6 (ATF6) are both ER-bound bZIP family transcription factors that are activated upon ER stress. Of interest, we observed that both curcumin treatment and SMILE overexpression only represses CREBH-mediated transactivation of the target gene but not ATF6-mediated transactivation. Knockdown of endogenous SMILE significantly releases the inhibitory effect of curcumin on CREBH transactivation. Intrinsic repressive activity of SMILE is observed in the Gal4 fusion system, and the intrinsic repressive domain is mapped to the C terminus of SMILE spanning amino acid residues 203-269, corresponding to the basic region leucine zipper (bZIP) domain. In vivo interaction assay revealed that through its bZIP domain, SMILE interacts with CREBH and inhibits its transcriptional activity. Interestingly, we observed that SMILE does not interact with ATF6. Furthermore, competition between SMILE and the coactivator peroxisome proliferator-activated receptor α (PGC-1α) on CREBH transactivation has been demonstrated in vitro and in vivo. Finally, chromatin immunoprecipitation assays revealed that curcumin decreases the binding of PGC-1α and CREBH on target gene promoter in a SMILE-dependent manner. Overall, for the first time we suggest a novel phenomenon that the curcumin/LKB1/AMPK/SMILE/PGC1α pathway differentially regulates ER stress-mediated gene transcription.

Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1.

PubMed

Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2006-02-07

bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid substitutions of R-X-X-S/T sites to Ala suppressed transactivation activity, and multiple substitution of these sites resulted in almost complete suppression of transactivation activity in transient assays. In contrast, substitution of the Ser/Thr residues to Asp resulted in high transactivation activity without exogenous ABA application. A phosphorylated, transcriptionally active form was achieved by substitution of Ser/Thr in all conserved R-X-X-S/T sites to Asp. Transgenic plants overexpressing the phosphorylated active form of AREB1 expressed many ABA-inducible genes, such as RD29B, without ABA treatment. These results indicate that the ABA-dependent multisite phosphorylation of AREB1 regulates its own activation in plants.

An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat.

PubMed Central

Kenney, S; Kamine, J; Markovitz, D; Fenrick, R; Pagano, J

1988-01-01

Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, we demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses. Images PMID:2830625

Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenney, S.; Kamine, J.; Markovitz, D.

Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, the authors demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBVmore » gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.« less

RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells.

PubMed

Kamato, Danielle; Bhaskarala, Venkata Vijayanand; Mantri, Nitin; Oh, Tae Gyu; Ling, Dora; Janke, Reearna; Zheng, Wenhua; Little, Peter J; Osman, Narin

2017-01-01

G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the β-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways.

Carbon starvation in glacial trees recovered from the La Brea tar pits, southern California

Treesearch

Joy K. Ward; John M. Harris; Thure E. Cerling; Alex Wiedenhoeft; Michael J. Lott; Maria-Denise Dearing; Joan B. Coltrain; James R. Ehleringer

2005-01-01

The Rancho La Brea tar pit fossil collection includes Juniperus (C3) wood specimens that 14C date between 7.7 and 55 thousand years (kyr) B.P., providing a constrained record of plant response for southern California during the last glacial period. Atmospheric CO2 concentration ([CO2]) ranged between 180 and 220 ppm during glacial periods, rose to 280 ppm before the...

Transactivation of the Brassica napus napin promoter by ABI3 requires interaction of the conserved B2 and B3 domains of ABI3 with different cis-elements: B2 mediates activation through an ABRE, whereas B3 interacts with an RY/G-box.

PubMed

Ezcurra, I; Wycliffe, P; Nehlin, L; Ellerström, M; Rask, L

2000-10-01

The transcriptional activator ABI3 is a key regulator of gene expression during embryo maturation in crucifers. In monocots, the related VP1 protein regulates the Em promoter synergistically with abscisic acid (ABA). We identified cis-elements in the Brassica napus napin napA promoter mediating regulation by ABI3 and ABA, by analyzing substitution mutation constructs of napA in transgenic tobacco plantlets ectopically expressing ABI3. In transient analysis using particle bombardment of tobacco leaf sections, a tetramer of the distB ABRE (abscisic acid-responsive element) mediated transactivation by ABI3 and ABI3-dependent response to ABA, whereas a tetramer of the composite RY/G complex, containing RY repeats and a G-box, mediated only ABA-independent transactivation by ABI3. Deletion of the conserved B2 and B3 domains of ABI3 abolished transactivation of napA by ABI3. The two domains of ABI3 interact with different cis-elements: B2 is necessary for ABA-independent and ABA-dependent activations through the distB ABRE, whereas B3 interacts with the RY/G complex. Thus B2 mediates the interaction of ABI3 with the protein complex at the ABRE. The regulation of napA by ABI3 differs from Em regulation by VP1, in that the B3 domain of ABI3 is essential for the ABA-dependent regulation of napA.

Glucocorticoid Repression of Inflammatory Gene Expression Shows Differential Responsiveness by Transactivation- and Transrepression-Dependent Mechanisms

PubMed Central

King, Elizabeth M.; Chivers, Joanna E.; Rider, Christopher F.; Minnich, Anne; Giembycz, Mark A.; Newton, Robert

2013-01-01

Binding of glucocorticoid to the glucocorticoid receptor (GR/NR3C1) may repress inflammatory gene transcription via direct, protein synthesis-independent processes (transrepression), or by activating transcription (transactivation) of multiple anti-inflammatory/repressive factors. Using human pulmonary A549 cells, we showed that 34 out of 39 IL-1β-inducible mRNAs were repressed to varying degrees by the synthetic glucocorticoid, dexamethasone. Whilst these repressive effects were GR-dependent, they did not correlate with either the magnitude of IL-1β-inducibility or the NF-κB-dependence of the inflammatory genes. This suggests that induction by IL-1β and repression by dexamethasone are independent events. Roles for transactivation were investigated using the protein synthesis inhibitor, cycloheximide. However, cycloheximide reduced the IL-1β-dependent expression of 13 mRNAs, which, along with the 5 not showing repression by dexamethasone, were not analysed further. Of the remaining 21 inflammatory mRNAs, cycloheximide significantly attenuated the dexamethasone-dependent repression of 11 mRNAs that also showed a marked time-dependence to their repression. Such effects are consistent with repression occurring via the de novo synthesis of a new product, or products, which subsequently cause repression (i.e., repression via a transactivation mechanism). Conversely, 10 mRNAs showed completely cycloheximide-independent, and time-independent, repression by dexamethasone. This is consistent with direct GR transrepression. Importantly, the inflammatory mRNAs showing attenuated repression by dexamethasone in the presence of cycloheximide also showed a significantly greater extent of repression and a higher potency to dexamethasone compared to those mRNAs showing cycloheximide-independent repression. This suggests that the repression of inflammatory mRNAs by GR transactivation-dependent mechanisms accounts for the greatest levels of repression and the most potent repression by dexamethasone. In conclusion, our data indicate roles for both transrepression and transactivation in the glucocorticoid-dependent repression of inflammatory gene expression. However, transactivation appears to account for the more potent and efficacious mechanism of repression by glucocorticoids on these IL-1β-induced genes. PMID:23349769

ΔN-P63α and TA-P63α exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites

PubMed Central

Foggetti, Giorgia; Raimondi, Ivan; Campomenosi, Paola; Menichini, Paola

2014-01-01

TP63 is a member of the TP53 gene family that encodes for up to ten different TA and ΔN isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulin-like folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA- and ΔN-P63α proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Since genotoxic stress can change relative ratio of TA- and ΔN-P63α protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses. PMID:24926492

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

PubMed

Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

2006-08-22

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

A novel p53 mutational hotspot in skin tumors from UV-irradiated Xpc mutant mice alters transactivation functions.

PubMed

Inga, Alberto; Nahari, Dorit; Velasco-Miguel, Susana; Friedberg, Errol C; Resnick, Michael A

2002-08-22

A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the functional consequences of the mouse T122-->L mutation when expressed either in mammalian cells or in the yeast Saccharomyces cerevisiae. Similar to a non-functional allele, high expression of the T122-->L allele in p53(-/-) mouse embryo fibroblasts and human Saos-2 cells failed to suppress growth. However, the T122-->L mutant p53 showed wild-type transactivation levels with Bax and MDM2 promoters when expressed in either cell type and retained transactivation of the p21 and the c-Fos promoters in one cell line. Using a recently developed rheostatable p53 induction system in yeast we assessed the T122-->L transactivation capacity at low levels of protein expression using 12 different p53 response elements (REs). Compared to wild-type p53 the T122-->L protein manifested an unusual transactivation pattern comprising reduced and enhanced activity with specific REs. The high incidence of the T122-->L mutant allele in the Xpc(-/-) background suggests that both genetic and epigenetic conditions may facilitate the emergence of particular functional p53 mutations. Furthermore, the approach that we have taken also provides for the dissection of functions that may be retained in many p53 tumor alleles.

Comparative evaluation of topical calcipotriol versus coal tar and salicylic acid ointment in chronic plaque psoriasis.

PubMed

Singh, Preeti; Gupta, Surabhi; Abidi, Afroz; Krishna, Arvind

2013-08-01

Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use. To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis. SETTING and Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital. The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse. It was done by paired t-test and independent sample t-test. The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

A transgenic model of transactivation by the Tax protein of HTLV-I.

PubMed

Bieberich, C J; King, C M; Tinkle, B T; Jay, G

1993-09-01

The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

Tristetraprolin Represses Estrogen Receptor α Transactivation in Breast Cancer Cells*

PubMed Central

Barrios-García, Tonatiuh; Tecalco-Cruz, Angeles; Gómez-Romero, Vania; Reyes-Carmona, Sandra; Meneses-Morales, Iván; León-Del-Río, Alfonso

2014-01-01

Estrogen receptor α (ERα) mediates the effects of 17β-estradiol (E2) in normal mammary gland, and it is a key participant in breast cancer tumor development. ERα transactivation activity is mediated by the synergistic interaction of two domains designated AF1 and AF2. The function of AF2 is to recruit coactivator and corepressor proteins that allow ERα to oscillate between the roles of transcriptional activator and repressor. In contrast, the mechanism responsible for AF-1 transcriptional activity is not completely understood. In this study, we identified tristetraproline (TTP) as a novel ERα-associated protein. TTP expression in MCF7 cells repressed ERα transactivation and reduced MCF7 cell proliferation and the ability of the cells to form tumors in a mouse model. We show that TTP transcriptional activity is mediated through its recruitment to the promoter region of ERα target genes and its interaction with histone deacetylases, in particular with HDAC1. TTP expression attenuates the coactivating activity of SRC-1, suggesting that exchange between TTP and other coactivators may play an important role in fine-tuning ERα transactivation. These results indicate that TTP acts as a bona fide ERα corepressor and suggest that this protein may be a contributing factor in the development of E2-dependent tumors in breast cancer. PMID:24737323

Heterotrimeric G proteins directly regulate MMP14/membrane type-1 matrix metalloprotease: a novel mechanism for GPCR-EGFR transactivation.

PubMed

Overland, Aaron C; Insel, Paul A

2015-04-17

Agonist stimulation of G protein-coupled receptors (GPCRs) can transactivate epidermal growth factor receptors (EGFRs), but the precise mechanisms for this transactivation have not been defined. Key to this process is the protease-mediated "shedding" of membrane-tethered ligands, which then activate EGFRs. The specific proteases and the events involved in GPCR-EGFR transactivation are not fully understood. We have tested the hypothesis that transactivation can occur by a membrane-delimited process: direct increase in the activity of membrane type-1 matrix metalloprotease (MMP14, MT1-MMP) by heterotrimeric G proteins, and in turn, the generation of heparin-binding epidermal growth factor (HB-EGF) and activation of EGFR. Using membranes prepared from adult rat cardiac myocytes and fibroblasts, we found that MMP14 activity is increased by angiotensin II, phenylephrine, GTP, and guanosine 5'-O-[γ-thio]triphosphate (GTPγS). MMP14 activation by GTPγS occurs in a concentration- and time-dependent manner, does not occur in response to GMP or adenosine 5'-[γ-thio]triphosphate (ATPγS), and is not blunted by inhibitors of Src, PKC, phospholipase C (PLC), PI3K, or soluble MMPs. This activation is specific to MMP14 as it is inhibited by a specific MMP14 peptide inhibitor and siRNA knockdown. MMP14 activation by GTPγS is pertussis toxin-sensitive. A role for heterotrimeric G protein βγ subunits was shown by using the Gβγ inhibitor gallein and the direct activation of recombinant MMP14 by purified βγ subunits. GTPγS-stimulated activation of MMP14 also results in membrane release of HB-EGF and the activation of EGFR. These results define a previously unrecognized, membrane-delimited mechanism for EGFR transactivation via direct G protein activation of MMP14 and identify MMP14 as a heterotrimeric G protein-regulated effector. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Coordinated P53 and Estrogen Receptor Cis-Regulation at an FLT1 Promoter SNP Is Specific to Genotoxic Stress and Estrogenic Compound

PubMed Central

Langen, Jan-Stephan; Schoenfelder, Gilbert; Resnick, Michael A.; Inga, Alberto

2010-01-01

Background Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a ½ site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an estrogen receptor (ER) ½ site response element (ERE1) 225 nt upstream to the RE-T. Methodology/Principal Findings Here we report the identification of a second ER ½ site (ERE2) located 145 bp downstream of the RE-T and establish that both EREs can impact p53-mediated transactivation of FLT1-T in a manner that is cell type and ER level dependent. Gene reporter assays and ChIP experiments conducted in the breast cancer-derived MCF7 cells revealed that the ERE2 site was sufficient for p53-mediated ERα recruitment and transactivation of the FLT1-T promoter/reporter construct. Surprisingly, unlike the case for other p53 target promoters, p53-mediated transactivation of FLT1-T constructs or expression of the endogenous FLT1 gene, as well as binding of p53 and ER at the promoter constructs, was inducible by doxorubicin but not by 5-fluorouracil. Furthermore, ER activity at FLT1-T was differentially affected by ER ligands, compared to a control TFF1/pS2 ER target promoter. The p53-related transcription factors (TFs) p73 and p63 had no effect on FLT1 transactivation. Conclusions/Significance We establish a new dimension to the p53 master regulatory network where p53-mediated transcription from a ½ site RE can be determined by ER binding at one or more cis-acting EREs in manner that is dependent on level of ER protein, the type of ER ligand and the specific p53-inducing agent. PMID:20422012

HMGB1-mediated DNA bending: Distinct roles in increasing p53 binding to DNA and the transactivation of p53-responsive gene promoters.

PubMed

Štros, Michal; Kučírek, Martin; Sani, Soodabeh Abbasi; Polanská, Eva

2018-03-01

HMGB1 is a chromatin-associated protein that has been implicated in many important biological processes such as transcription, recombination, DNA repair, and genome stability. These functions include the enhancement of binding of a number of transcription factors, including the tumor suppressor protein p53, to their specific DNA-binding sites. HMGB1 is composed of two highly conserved HMG boxes, linked to an intrinsically disordered acidic C-terminal tail. Previous reports have suggested that the ability of HMGB1 to bend DNA may explain the in vitro HMGB1-mediated increase in sequence-specific DNA binding by p53. The aim of this study was to reinvestigate the importance of HMGB1-induced DNA bending in relationship to the ability of the protein to promote the specific binding of p53 to short DNA duplexes in vitro, and to transactivate two major p53-regulated human genes: Mdm2 and p21/WAF1. Using a number of HMGB1 mutants, we report that the HMGB1-mediated increase in sequence-specific p53 binding to DNA duplexes in vitro depends very little on HMGB1-mediated DNA bending. The presence of the acidic C-terminal tail of HMGB1 and/or the oxidation of the protein can reduce the HMGB1-mediated p53 binding. Interestingly, the induction of transactivation of p53-responsive gene promoters by HMGB1 requires both the ability of the protein to bend DNA and the acidic C-terminal tail, and is promoter-specific. We propose that the efficient transactivation of p53-responsive gene promoters by HMGB1 depends on complex events, rather than solely on the promotion of p53 binding to its DNA cognate sites. Copyright © 2018 Elsevier B.V. All rights reserved.

Transactivation mediated by B-Myb is dependent on TAF(II)250.

PubMed

Bartusel, Thorsten; Klempnauer, Karl-Heinz

2003-05-15

B-Myb is a highly conserved member of the Myb family of transcription factors, which has been implicated in cell cycle regulation. B-Myb is expressed in most proliferating cells and its activity is highly regulated around the G1/S-phase border of the cell cycle. It is generally assumed that B-Myb regulates the expression of genes that are crucial for cell proliferation; however, the identity of these genes, the molecular mechanisms by which B-Myb stimulates their expression and the involvement of other proteins have not been sufficiently clarified. We have employed the hamster cell line ts13 as a tool to demonstrate a functional link between B-Myb and the coactivator TAF(II)250, a key component of the transcriptional machinery which itself is essential for cell proliferation. ts13 cells express a point-mutated version of TAF(II)250 whose intrinsic histone acetyl transferase activity is temperature sensitive. Transactivation of Myb-responsive reporter genes by B-Myb is temperature-dependent in ts13 cells but not in ts13 cells, which have been rescued by transfection with an expression vector for wild-type TAF(II)250. Furthermore, B-Myb and TAF(II)250 can be coprecipitated, suggesting that both proteins are present in a complex. The formation of this complex is dependent on the DNA-binding domain of B-Myb and not on its transactivation domain. Taken together, these observations provide the first evidence that the coactivator TAF(II)250 is involved in the activation of Myb responsive promoters by B-Myb. The finding that B-Myb transactivation is dependent on a key coactivator involved in cell cycle control is consistent with and strengthens the idea that B-Myb plays a crucial role as a transcription factor in proliferating cells.

In brown adipocytes, adrenergically induced β{sub 1}-/β{sub 3}-(G{sub s})-, α{sub 2}-(G{sub i})- and α{sub 1}-(G{sub q})-signalling to Erk1/2 activation is not mediated via EGF receptor transactivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanling; Fälting, Johanna M.; Mattsson, Charlotte L.

2013-10-15

Brown adipose tissue is unusual in that the neurotransmitter norepinephrine influences cell destiny in ways generally associated with effects of classical growth factors: regulation of cell proliferation, of apoptosis, and progression of differentiation. The norepinephrine effects are mediated through G-protein-coupled receptors; further mediation of such stimulation to e.g. Erk1/2 activation is in cell biology in general accepted to occur through transactivation of the EGF receptor (by external or internal pathways). We have examined here the significance of such transactivation in brown adipocytes. Stimulation of mature brown adipocytes with cirazoline (α{sub 1}-adrenoceptor coupled via G{sub q}), clonidine (α{sub 2} via G{submore » i}) or CL316243 (β{sub 3} via G{sub s}) or via β{sub 1}-receptors significantly activated Erk1/2. Pretreatment with the EGF receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2 activation induced by any of these adrenergic agonists (although it fully abolished EGF-induced Erk1/2 activation), demonstrating absence of EGF receptor-mediated transactivation. Results with brown preadipocytes (cells in more proliferative states) were not qualitatively different. Joint stimulation of all adrenoceptors with norepinephrine did not result in synergism on Erk1/2 activation. AG1478 action on EGF-stimulated Erk1/2 phosphorylation showed a sharp concentration–response relationship (IC{sub 50} 0.3 µM); a minor apparent effect of AG1478 on norepinephrine-stimulated Erk1/2 phosphorylation showed nonspecific kinetics, implying caution in interpretation of partial effects of AG1478 as reported in other systems. Transactivation of the EGF receptor is clearly not a universal prerequisite for coupling of G-protein coupled receptors to Erk1/2 signalling cascades. - Highlights: • In brown adipocytes, norepinephrine regulates proliferation, apoptosis, differentiation. • EGF receptor transactivation is supposed to mediate GPCR-induced Erk1/2 activation. • α{sub 1}-, α{sub 2}-, β{sub 1}-, β{sub 3}-adrenoceptors all activate Erk1/2—but EGF receptor transactivation is not involved. • Adrenergic regulation of proliferation, apoptosis, differentiation must utilize cell-specific pathways in brown adipocytes. • EGF receptor transactivation is not universal in mediating GPCR-induced Erk1/2 activation.« less

Coal tar phototherapy for psoriasis reevaluated: erythemogenic versus suberythemogenic ultraviolet with a tar extract in oil and crude coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, N.J.; Wortzman, M.S.; Breeding, J.

1983-06-01

Recent studies have questioned the therapeutic value of coal tar versus ultraviolet (UV) radiation and their relative necessity in phototherapy for psoriasis. In this investigation, different aspects of tar phototherapy have been studied in single-blind bilateral paired comparison studies. The effects of 1% crude coal tar were compared with those of petrolatum in conjunction with erythemogenic and suberythemogenic doses of ultraviolet light (UVB) using a FS72 sunlamp tubed cabinet. Crude coal tar was clinically superior to petrolatum with suberythemogenic ultraviolet. With the erythemogenic UVB, petrolatum was equal in efficacy to crude coal tar. Suberythemogenic UVB was also used adjunctively tomore » compare the effects of a 5% concentration of a tar extract in an oil base to 5% crude coal tar in petrolatum or the oil base without tar. The tar extract in oil plus suberythemogenic UVB produced significantly more rapid improvement than the oil base plus UVB. The direct bilateral comparison of equal concentrations of tar extract in oil base versus crude coal tar in petrolatum in a suberythemogenic UV photo regimen revealed no statistical differences between treatments. In a study comparing tar extract in oil and the oil base without ultraviolet radiation, the tar extract in oil side responded more rapidly.« less

Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

PubMed

Keller, H; Givel, F; Perroud, M; Wahli, W

1995-07-01

Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

Crystallization and preliminary X-ray diffraction analysis of the periplasmic domain of the Escherichia coli aspartate receptor Tar and its complex with aspartate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mise, Takeshi; Matsunami, Hideyuki; Samatey, Fadel A.

The periplasmic domain of the E. coli aspartate receptor Tar was cloned, expressed, purified and crystallized with and without bound ligand. The crystals obtained diffracted to resolutions of 1.58 and 1.95 Å, respectively. The cell-surface receptor Tar mediates bacterial chemotaxis toward an attractant, aspartate (Asp), and away from a repellent, Ni{sup 2+}. To understand the molecular mechanisms underlying the induction of Tar activity by its ligands, the Escherichia coli Tar periplasmic domain with and without bound aspartate (Asp-Tar and apo-Tar, respectively) were each crystallized in two different forms. Using ammonium sulfate as a precipitant, crystals of apo-Tar1 and Asp-Tar1 weremore » grown and diffracted to resolutions of 2.10 and 2.40 Å, respectively. Alternatively, using sodium chloride as a precipitant, crystals of apo-Tar2 and Asp-Tar2 were grown and diffracted to resolutions of 1.95 and 1.58 Å, respectively. Crystals of apo-Tar1 and Asp-Tar1 adopted space group P4{sub 1}2{sub 1}2, while those of apo-Tar2 and Asp-Tar2 adopted space groups P2{sub 1}2{sub 1}2{sub 1} and C2, respectively.« less

Thrombin-induced p38 mitogen-activated protein kinase activation is mediated by epidermal growth factor receptor transactivation pathway

PubMed Central

Kanda, Yasunari; Mizuno, Katsushige; Kuroki, Yasutomi; Watanabe, Yasuhiro

2001-01-01

Thrombin is a potent mitogen for vascular smooth muscle cells (VSMC) and has been implicated its pathogenic role in vascular remodelling. However, the signalling pathways by which thrombin mediates its mitogenic response are not fully understood.We have previously reported that thrombin activates p38 mitogen-activated protein kinase (p38 MAPK) by a tyrosine kinase-dependent mechanism, and that p38 MAPK has a role in thrombin-induced mitogenic response in rat VSMC.In the present study, we examine the involvement of epidermal growth factor (EGF) receptor in thrombin-induced p38 MAPK activation. We found that thrombin induced EGF receptor tyrosine phosphorylation (transactivation) in A10 cells, a clonal VSMC cell line. A selective inhibitor of EGF receptor kinase (AG1478) inhibited the p38 MAPK activation in a dose-dependent manner, whereas it had no effect on the response to platelet-derived growth factor (PDGF). EGF receptor phosphorylation induced by thrombin was inhibited by BAPTA-AM and GF109203X, which suggest a requirement for intracellular Ca2+ increase and protein kinase C.We next examined the effect of AG1478 on thrombin-induced DNA synthesis. AG1478 inhibited thrombin-induced DNA synthesis in a dose-dependent manner. In contrast, PDGF-induced DNA synthesis was not affected by AG1478.In conclusion, these data suggest that the EGF receptor transactivation and subsequent p38 MAPK activation is required for thrombin-induced proliferation of VSMC. PMID:11309236

Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.

2008-11-14

REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

Smokers' knowledge and understanding of advertised tar numbers: health policy implications.

PubMed

Cohen, J B

1996-01-01

This article examines health policy implications of providing smokers with numerical tar yield information in cigarette advertising. Results of a national probability telephone survey regarding smokers' knowledge and understanding of numerical tar yields and deliveries are reported. Few smokers knew the tar level of their own cigarettes (the exception being smokers of 1- to 5-mg tar cigarettes), and a majority could not correctly judge the relative tar levels of cigarettes. Smokers were unsure whether switching to lower-tar cigarettes would reduce their personal health risks. Many smokers relied on absolute numbers in making trade-offs between number of cigarettes smoked and their tar levels, thus confusion machine-rated tar-yields with actual amounts ingested. The wisdom of the present method of providing tar and nicotine numbers in ads and recommendations for modifying the test protocol are now under discussion. This research indicates that these tar numbers and their implications are poorly understood. The paper recommends revisions in tar ratings to make them more useful and a required statement on cigarette packages to more explicitly relate tar levels to major health risks.

Smokers' knowledge and understanding of advertised tar numbers: health policy implications.

PubMed Central

Cohen, J B

1996-01-01

OBJECTIVES. This article examines health policy implications of providing smokers with numerical tar yield information in cigarette advertising. METHODS. Results of a national probability telephone survey regarding smokers' knowledge and understanding of numerical tar yields and deliveries are reported. RESULTS. Few smokers knew the tar level of their own cigarettes (the exception being smokers of 1- to 5-mg tar cigarettes), and a majority could not correctly judge the relative tar levels of cigarettes. Smokers were unsure whether switching to lower-tar cigarettes would reduce their personal health risks. Many smokers relied on absolute numbers in making trade-offs between number of cigarettes smoked and their tar levels, thus confusion machine-rated tar-yields with actual amounts ingested. CONCLUSIONS. The wisdom of the present method of providing tar and nicotine numbers in ads and recommendations for modifying the test protocol are now under discussion. This research indicates that these tar numbers and their implications are poorly understood. The paper recommends revisions in tar ratings to make them more useful and a required statement on cigarette packages to more explicitly relate tar levels to major health risks. PMID:8561236

Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax of human T-cell leukemia virus type I.

PubMed

Huang, Y; Ohtani, K; Iwanaga, R; Matsumura, Y; Nakamura, M

2001-03-01

Cyclins are one of the pivotal determinants regulating cell cycle progression. We previously reported that the trans-activator Tax of human T-cell leukemia virus type I (HTLV-I) induces endogenous cyclin D2 expression along with cell cycle progression in a resting human T-cell line, Kit 225, suggesting a role of cyclin D2 in Tax-mediated cell cycle progression. The cyclin D2 gene has a typical E2F binding element, raising the possibility that induction of cyclin D2 expression is a consequence of cell cycle progression. In this study, we examined the role and molecular mechanism of induction of the endogenous human cyclin D2 gene by Tax. Introduction of p19(INK4d), a cyclin dependent kinase (CDK) inhibitor of the INK4 family specific for D-type CDK, inhibited Tax-mediated activation of E2F, indicating requirement of D-type CDK in Tax-mediated activation of E2F. Previously indicated E2F binding element and two NF-kappaB-like binding elements in the 1.6 kbp cyclin D2 promoter fragment had little, if any, effect on responsiveness to Tax. We found that trans-activation of the cyclin D2 promoter by Tax was mainly mediated by a newly identified NF-kappaB-like element with auxiliary contribution of a CRE-like element residing in sequences downstream of -444 which were by themselves sufficient for trans-activation by Tax. These results indicate that Tax directly trans-activates the cyclin D2 gene, resulting in growth promotion and perhaps leukemogenesis through activation of D-type CDK.

A liver X receptor (LXR)-{beta} alternative splicing variant (LXRBSV) acts as an RNA co-activator of LXR-{beta}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Koshi, E-mail: khashi@med.gunma-u.ac.jp; Ishida, Emi; Matsumoto, Shunichi

2009-12-25

We report the isolation and functional characterization of a novel transcriptional co-activator, termed LXRBSV. LXRBSV is an alternative splicing variant of liver X receptor (LXR)-{beta} LXRBSV has an intronic sequence between exons 2 and 3 in the mouse LXR-{beta} gene. The LXRBSV gene is expressed in various tissues including the liver and brain. We sub-cloned LXRBSV into pSG5, a mammalian expression vector, and LXRBSV in pSG5 augmented human Sterol Response Element Binding Protein (SREBP)-1c promoter activity in HepG2 cells in a ligand (TO901317) dependent manner. The transactivation mediated by LXRBSV is selective for LXR-{beta}. The LXRBSV protein was deduced tomore » be 64 amino acids in length; however, a GAL4-LXRBSV fusion protein was not able to induce transactivation. Serial deletion constructs of LXRBSV demonstrated that the intronic sequence inserted in LXRBSV is required for its transactivation activity. An ATG mutant of LXRBSV was able to induce transactivation as wild type. Furthermore, LXRBSV functions in the presence of cycloheximide. Taken together, we have concluded that LXRBSV acts as an RNA transcript not as a protein. In the current study, we have demonstrated for the first time that an alternative splicing variant of a nuclear receptor acts as an RNA co-activator.« less

Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis.

PubMed

Sharifat, Narges; Mohammad Zadeh, Ghorban; Ghaffari, Mohammad-Ali; Dayati, Parisa; Kamato, Danielle; Little, Peter J; Babaahmadi-Rezaei, Hossein

2017-01-01

G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TβRI in bovine aortic endothelial cells (BAECs). The in-vitro model used BAECs. Signalling intermediate phospho-Smad2 in the carboxy terminal was detected and quantified by Western blotting. ET-1 treatment of BAECs resulted in a time and concentration-dependent increase in pSmad2C. Peak phosphorylation was evident with 100 nm treatment of ET-1 at 4-6 h. TβRI antagonist, SB431542 inhibited ET-1-mediated pSmad2C. In the presence of bosentan, a mixed ET A and ET B receptor antagonist ET-1-mediated pSmad2C levels were inhibited. The ET-mediated pSmad2C was blocked by the protein synthesis inhibitor, cycloheximide. In BAECs, ET-1 via the ETB receptor is involved in transactivation of the TβRI. The transactivation-dependent response is dependent upon de novo protein synthesis. © 2016 Royal Pharmaceutical Society.

The temporal relationship between advertising and sales of low‐tar cigarettes

PubMed Central

Reed, Mark B; Anderson, Christy M; Burns, David M

2006-01-01

Objective and hypothesis To determine whether a temporal relationship exists between the advertising and sales of low‐tar cigarettes. It was hypothesised that increases in the advertising of low‐tar cigarettes would precede increases in sales for these cigarettes. Methods The themes of cigarette advertisements were reviewed and coded for 20 low‐tar cigarette brands advertised in 13 widely read magazines in the US between 1960 and 1996. These 20 brands represented most of the low‐tar cigarette advertisements and cigarette sales from 1967 to 1996. Cigarette sales data were obtained from the 1994 Maxwell report that summarises all cigarette sales from 1925 to 1990. If the advertisement referred to the low‐tar attributes of the cigarette advertised, the advertisement was coded as having a low‐tar theme and was included in the analysis. Results Five different graphical presentations of the relationship between the advertising and sales of the 20 low‐tar cigarette brands showed a temporal relationship between low‐tar advertising and sales for these brands. This relationship was observed for brands that introduced a low‐tar alternative into an existing brand family (eg, Marlboro Light) and for new exclusively low‐tar brands (eg, Carlton). Despite large increases in the advertising for the exclusively low‐tar brands, sales of these brands remained low relative to sales of the low‐tar alternative brands. Conclusions Increases in print advertising of 20 of the most popular low‐tar cigarette brands were followed by increases in sales for these cigarettes. Despite increases in the advertising of exclusively low‐tar brands in the mid‐1970s and early 1980s, the sales of these brands never matched the sales of the low‐tar alternative brands. This suggests that it may have been easier to get smokers to switch to low‐tar brands within a brand family compared with entirely new low‐tar brands. Over the past 30 years, the marketing of low‐tar cigarettes as a healthier alternative to higher‐tar cigarettes has resulted in these brands dominating the market, and may have kept concerned smokers from quitting. PMID:17130371

The temporal relationship between advertising and sales of low-tar cigarettes.

PubMed

Reed, Mark B; Anderson, Christy M; Burns, David M

2006-12-01

To determine whether a temporal relationship exists between the advertising and sales of low-tar cigarettes. It was hypothesised that increases in the advertising of low-tar cigarettes would precede increases in sales for these cigarettes. The themes of cigarette advertisements were reviewed and coded for 20 low-tar cigarette brands advertised in 13 widely read magazines in the US between 1960 and 1996. These 20 brands represented most of the low-tar cigarette advertisements and cigarette sales from 1967 to 1996. Cigarette sales data were obtained from the 1994 Maxwell report that summarises all cigarette sales from 1925 to 1990. If the advertisement referred to the low-tar attributes of the cigarette advertised, the advertisement was coded as having a low-tar theme and was included in the analysis. Five different graphical presentations of the relationship between the advertising and sales of the 20 low-tar cigarette brands showed a temporal relationship between low-tar advertising and sales for these brands. This relationship was observed for brands that introduced a low-tar alternative into an existing brand family (eg, Marlboro Light) and for new exclusively low-tar brands (eg, Carlton). Despite large increases in the advertising for the exclusively low-tar brands, sales of these brands remained low relative to sales of the low-tar alternative brands. Increases in print advertising of 20 of the most popular low-tar cigarette brands were followed by increases in sales for these cigarettes. Despite increases in the advertising of exclusively low-tar brands in the mid-1970s and early 1980s, the sales of these brands never matched the sales of the low-tar alternative brands. This suggests that it may have been easier to get smokers to switch to low-tar brands within a brand family compared with entirely new low-tar brands. Over the past 30 years, the marketing of low-tar cigarettes as a healthier alternative to higher-tar cigarettes has resulted in these brands dominating the market, and may have kept concerned smokers from quitting.

The effects of heavy metal mine drainage on population size structure, reproduction, and condition of western mosquitofish, Gambusia affinis.

PubMed

Franssen, Courtney M

2009-07-01

Anthropogenic degradation of aquatic environments worldwide results in disturbed habitats, altered communities, and stressed populations. Surface waters located in an abandoned lead-zinc mining district in northeastern Oklahoma are no exception. This study examines the reproductive and somatic responses of a pollution-tolerant fish, the western mosquitofish, Gambusia affinis (Teleostei: Poeciliidae), living in mine outflow waters contaminated by heavy metals. Populations were sampled from four streams, which were classified into three habitat types. Populations from Tar Creek and an Unnamed Tributary of Tar Creek receive direct input of mine drainage, while populations living in reference creeks are not known to have mining influence. The influence of mine drainage directly or indirectly (via altered competitor and predator regimes or changes in food availability) affects G. affinis at both the population and the individual level. Metal-contaminated sites had reduced proportions of males and reproductively active females and altered male population size structures. Individual-level effects were apparent, as all G. affinis from Tar Creek invested less in liver weights, and mature males and reproductively active females from Tar Creek invested less in gonad weights. Furthermore, males from impacted sites were significantly lighter than those from reference creeks. Gravid females from Tar Creek had smaller clutch sizes, but average embryo weight did not differ among streams.

Structural insights into the cTAR DNA recognition by the HIV-1 nucleocapsid protein: role of sugar deoxyriboses in the binding polarity of NC

PubMed Central

Bazzi, Ali; Zargarian, Loussiné; Chaminade, Françoise; Boudier, Christian; De Rocquigny, Hughes; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

2011-01-01

An essential step of the reverse transcription of the HIV-1 genome is the first strand transfer that requires the annealing of the TAR RNA hairpin to the cTAR DNA hairpin. HIV-1 nucleocapsid protein (NC) plays a crucial role by facilitating annealing of the complementary hairpins. Using nuclear magnetic resonance and gel retardation assays, we investigated the interaction between NC and the top half of the cTAR DNA (mini-cTAR). We show that NC(11-55) binds the TGG sequence in the lower stem that is destabilized by the adjacent internal loop. The 5′ thymine interacts with residues of the N-terminal zinc knuckle and the 3′ guanine is inserted in the hydrophobic plateau of the C-terminal zinc knuckle. The TGG sequence is preferred relative to the apical and internal loops containing unpaired guanines. Investigation of the DNA–protein contacts shows the major role of hydrophobic interactions involving nucleobases and deoxyribose sugars. A similar network of hydrophobic contacts is observed in the published NC:DNA complexes, whereas NC contacts ribose differently in NC:RNA complexes. We propose that the binding polarity of NC is related to these contacts that could be responsible for the preferential binding to single-stranded nucleic acids. PMID:21227929

Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration.

PubMed

Kukreja, L; Shahidehpour, R; Kim, G; Keegan, J; Sadleir, K R; Russell, T; Csernansky, J; Mesulam, M; Vassar, R J; Wang, L; Dong, H; Geula, C

2018-05-28

Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) employing tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43 which is placed downstream of the tetracycline response element (TRE). The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in post-weaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3 and loss of neurons. The atrophy associated with tTA expression was rescuable by tetracycline analog, doxycycline in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration and behavioral deficits in FTLD. SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing genes. Here, we report on a mouse model that overexpresses human TDP-43 using tTA and attempt to recapitulate features of TDP-43 pathology present in human FTLD. The tTA expression system is problematic, resulting in dramatic degeneration of the hippocampus. Thus, our study adds a note of caution for the use of the tTA system. However, since FTLD is primarily characterized by cortical degeneration and our mouse model shows significant atrophy in most cortical areas due to human TDP-43 overexpression, our animal model remains useful for providing critical insight on this human disease. Copyright © 2018 the authors.

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

PubMed

Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

Topical tar: Back to the future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paghdal, K.V.; Schwartz, R.A.

2009-08-15

The use of medicinal tar for dermatologic disorders dates back to the ancient times. Although coal tar is utilized more frequently in modern dermatology, wood tars have also been widely employed. Tar is used mainly in the treatment of chronic stable plaque psoriasis, scalp psoriasis, atopic dermatitis, and seborrheic dermatitis, either alone or in combination therapy with other medications, phototherapy, or both. Many modifications have been made to tar preparations to increase their acceptability, as some dislike its odor, messy application, and staining of clothing. One should consider a tried and true treatment with tar that has led to clearingmore » of lesions and prolonged remission times. Occupational studies have demonstrated the carcinogenicity of tar; however, epidemiologic studies do not confirm similar outcomes when used topically. This article will review the pharmacology, formulations, efficacy, and adverse effects of crude coal tar and other tars in the treatment of selected dermatologic conditions.« less

The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

PubMed Central

Khong, Hung T.; Rosenberg, Steven A.

2008-01-01

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease.

PubMed

Luty, Agnes A; Kwok, John B J; Dobson-Stone, Carol; Loy, Clement T; Coupland, Kirsten G; Karlström, Helena; Sobow, Tomasz; Tchorzewska, Joanna; Maruszak, Aleksandra; Barcikowska, Maria; Panegyres, Peter K; Zekanowski, Cezary; Brooks, William S; Williams, Kelly L; Blair, Ian P; Mather, Karen A; Sachdev, Perminder S; Halliday, Glenda M; Schofield, Peter R

2010-11-01

Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia. Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma (FUS) protein. Our objective was to identify the causative gene in an FTLD-MND pedigree with no mutations in known dementia genes. A mutation screen of candidate genes, luciferase assays, and quantitative polymerase chain reaction (PCR) was performed to identify the biological role of the putative mutation. Neuropathological characterization of affected individuals and western blot studies of cell lines were performed to identify the pathological mechanism of the mutation. We identified a nonpolymorphic mutation (c.672*51G>T) in the 3'-untranslated region (UTR) of the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected individuals from the FTLD-MND pedigree. The c.672*51G>T mutation increased gene expression by 1.4-fold, corresponding with a significant 1.5-fold to 2-fold change in the SIGMAR1 transcript or Sigma-1 protein in lymphocyte or brain tissue. Brains of SIGMAR1 mutation carriers displayed a unique pathology with cytoplasmic inclusions immunopositive for either TDP-43 or FUS but not Sigma-1. Overexpression of SIGMAR1 shunted TDP-43 and FUS from the nucleus to the cytoplasm by 2.3-fold and 5.2-fold, respectively. Treatment of cells with Sigma-1 ligands significantly altered translocation of TDP-43 by up to 2-fold. SIGMAR1 is a causative gene for familial FTLD-MND with a unique neuropathology that differs from other FTLD and MND cases. Our findings also suggest Sigma-1 drugs as potential treatments for the TDP-43/FUS proteinopathies.

Tar Management and Recycling in Biomass Gasification and Syngas Purification

NASA Astrophysics Data System (ADS)

McCaffrey, Zach

Removal of tars is critical to the design and operation of biomass gasification systems as most syngas utilization processing equipment (e.g. internal combustion engines, gas turbines, fuel cells, and liquid fuel synthesis reactors) have a low tolerance for tar. Capturing and disposal of tar is expensive due to equipment costs, high hazardous waste disposal costs where direct uses cannot be found, and system energy losses incurred. Water scrubbing is an existing technique commonly used in gasification plants to remove contaminants and tar; however using water as the absorbent is non-ideal as tar compounds have low or no water solubility. Hydrophobic solvents can improve scrubber performance and this study evaluated tar solubility in selected solvents using slip-streams of untreated syngas from a laboratory fluidized bed reactor operated on almond composite feedstock using both air and steam gasification. Tar solubility was compared with Hansen's solubility theory to examine the extent to which the tar removal can be predicted. As collection of tar without utilization leads to a hazardous waste problem, the study investigated the effects of recycling tars back into the gasifier for destruction. Prior to experiments conducted on tar capture and recycle, characterizations of the air and steam gasification of the almond composite mix were made. This work aims to provide a better understanding of tar collection and solvent selection for wet scrubbers, and to provide information for designing improved tar management systems for biomass gasification.

Assessing the Utilization of Total Ankle Replacement in the United States.

PubMed

Reddy, Sudheer; Koenig, Lane; Demiralp, Berna; Nguyen, Jennifer T; Zhang, Qian

2017-06-01

Total ankle arthroplasty (TAR) has been shown to be a cost-effective procedure relative to conservative management and ankle arthrodesis. Although its use has grown considerably over the last 2 decades, it is less common than arthrodesis. The purpose of this investigation was to analyze the cost and utilization of TAR across hospitals. Our analytical sample consisted of Medicare claims data from 2011 and 2012 for Inpatient Prospective Payment System hospitals. Outcome variables of interest were the likelihood of a hospital performing TAR, the volume of TAR cases, TAR hospital costs, and hospital profit margins. Data from the 2010 Cost Report and Medicare inpatient claims were utilized to compute average margins for TAR cases and overall hospital margins. TAR cost was calculated based on the all payer cost-to-charge ratio for each hospital in the Cost Report. Nationwide Inpatient Sample data were used to generate descriptive statistics on all TAR patients across payers. Medicare participants accounted for 47.5% of the overall population of TAR patients. Average implant cost was $13 034, accounting for approximately 70% of the total all-payer cost. Approximately, one-third of hospitals were profitable with respect to primary TAR. Profitable hospitals had lower total costs and higher payments leading to a difference in profit of approximately $11 000 from TAR surgeries between profitable and nonprofitable hospitals. No difference was noted with respect to length of stay or number of cases performed between profitable and nonprofitable hospitals. TAR surgeries were more likely to take place in large and major teaching hospitals. Among hospitals performing at least 1 TAR, the margin on TAR cases was positively associated with the total number of TARs performed by a hospital. There is an overall significant financial burden associated with performing TAR with many health systems failing to demonstrate profitability despite its increased utilization. While additional factors such as improved patient outcomes may be driving utilization of TAR, financial barriers may exist that can affect utilization of TAR across health systems. Level III, comparative study.

Comparative analysis of open and robotic transversus abdominis release for ventral hernia repair.

PubMed

Bittner, James G; Alrefai, Sameer; Vy, Michelle; Mabe, Micah; Del Prado, Paul A R; Clingempeel, Natasha L

2018-02-01

Transversus abdominis release (TAR) is a safe, effective strategy to repair complex ventral incisional hernia (VIH); however, open TAR (o-TAR) often necessitates prolonged hospitalization. Robot-assisted TAR (r-TAR) may benefit short-term outcomes and shorten convalescence. This study compares 90-day outcomes of o-TAR and r-TAR for VIH repair. A single-center, retrospective review of patients who underwent o-TAR or r-TAR for VIH from 2015 to 2016 was conducted. Patient and hernia characteristics, operative data, and 90-day outcomes were compared. The primary outcome was hospital length of stay, and secondary metrics were morbidity, surgical site events, and readmission. Overall, 102 patients were identified (76 o-TAR and 26 r-TAR). Patients were comparable regarding age, gender, body mass index, and the presence of co-morbidities. Diabetes was more common in the open group (22.3 vs. 0%, P = 0.01). Most VIH defects were midline (89.5 vs. 83%, P = 0.47) and recurrent (52.6 vs. 58.3%, P = 0.65). Hernia characteristics were similar regarding mean defect size (260 ± 209 vs. 235 ± 107 cm 2 , P = 0.55), mesh removal, and type/size mesh implanted. Average operative time was longer in the r-TAR cohort (287 ± 121 vs. 365 ± 78 min, P < 0.01) despite most receiving mesh fixation with fibrin sealant alone (18.4 vs. 91.7%, P < 0.01). r-TAR trended toward lower morbidity (39.2 vs. 19.2%, P = 0.09), less severe complications, and similar rates of surgical site events and readmission (6.6 vs. 7.7%, P = 1.00). In addition, r-TAR resulted in a significantly shorter median hospital length of stay compared to o-TAR (6 days, 95% CI 5.9-8.3 vs. 3 days, 95% CI 3.2-4.3). In select patients, the robotic surgical platform facilitates a safe, minimally invasive approach to complex abdominal wall reconstruction, specifically TAR. Robot-assisted TAR for VIH offers the short-term benefits of low morbidity and decreased hospital length of stay compared to open TAR.

Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, San San; Crabb, Simon J.; Janghra, Nari

2007-09-10

In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1{alpha},25-dihydroxyvitamin D{sub 3.} BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified themore » nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1{alpha},25-dihydroxyvitamin D{sub 3}. By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis.« less

Method for treatment of tar-bearing fuel gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frauen, L.L.; Kasper, S.

1986-01-07

A process is described of producing a fuel gas which contains condensable tar vapor when it leaves a gasifier, the improvement wherein the tar-bearing gases are treated to remove tar therefrom. The process consists of: (a) continuously conducting hot fuel gas from a gasifier to and discharging it into a spray chamber where the hot tar-bearing gas is contacted with a fine spray of water thereby cooling the tar vapor and evaporating the water to produce a fog-like dispersion of tar in an atmosphere of fuel gas with the temperature in the spray chamber maintained above the dew point ofmore » water; (b) continuously transferring the fuel gas and the dispersion of tar and water to an electrostatic precipitator and precipitating therein at least most of the condensed tar as a liquid; (c) removing the liquid tar so precipitated and conducting at least most of it to a tar burner; (d) burning the tar with no more than the stoichiometric supply of oxygen provided by air to produce oxygen-free and tar-free hot combustion gases; (e) conducting the hot combustion gases directly into a mixer into which the fuel gas and water vapor flows from the precipitator, thereby adding to the fuel gas the sensible heat of the combustion gases; and (f) conducting the mixture so produced to a place of use as a hot fuel gas mixture.« less

Coal Tar and Coal-Tar Pitch

Cancer.gov

Learn about coal-tar products, which can raise your risk of skin cancer, lung cancer, and other types of cancer. Examples of coal-tar products include creosote, coal-tar pitch, and certain preparations used to treat skin conditions such as eczema, psoriasis, and dandruff.

Final safety assessment of Coal Tar as used in cosmetics.

PubMed

2008-01-01

Coal Tar is a semisolid by-product obtained in the destructive distillation of bituminous coal, which functions in cosmetic products as a cosmetic biocide and denaturant--antidandruff agent is also listed as a function, but this is considered an over-the-counter (OTC) drug use. Coal Tar is a nearly black, viscous liquid, heavier than water, with a naphthalene-like odor and a sharp burning taste, produced in cooking ovens as a by-product in the manufacture of coke. Crude Coal Tar is composed of 48% hydrocarbons, 42% carbon, and 10% water. In 2002, Coal Tar was reported to the Food and Drug Administration (FDA) to be used in four formulations, all of which appear to be OTC drug products. Coal Tar is monographed by the FDA as Category I (safe and effective) OTC drug ingredient for use in the treatment of dandruff, seborrhoea, and psoriasis. Coal Tar is absorbed through the skin of animals and humans and is systemically distributed. In short-term studies, mice fed a diet containing Coal Tar found it unpalatable, but no adverse effects were reported other than weight loss; rats injected with Coal Tar experienced malaise in one study and decreased water intake and increased liver weights in another; rabbits injected with Coal Tar residue experienced eating avoidance, respiratory difficulty, sneezing, and weight loss. In a subchronic neurotoxicity study using mice, a mixture of phenols, cresols, and xylenols at concentrations approximately equal to those expected in Coal Tar extracts produced regionally selective effects, with a rank order of corpus striatum > cerebellum > cerebral cortex. Coal Tar applied to the backs of guinea pigs increases epidermal thickness. Painting female rabbits with tar decreases the absolute and relative weights of the ovaries and decreased the number of interstitial cells in the ovary. Four therapeutic Coal Tar preparations used in the treatment of psoriasis were mutagenic in the Ames assay. Urine and blood from patients treated with Coal Tar were genotoxic in bacterial assays. Coal Tar was genotoxic in a mammalian genotoxicity assay and induced DNA adducts in various tissue types. Chronic exposure of mice to Coal Tar significantly decreased survival and liver neoplasms were seen in a significant dose-related trend; in other studies using mice lung tumors and perianal skin cancers were found. Coal Tar was comedogenic in three small clinical studies. Folliculitis is associated with the prolonged use of some tars. Several published reports describe cases of contact sensitivity to Coal Tar. Polycyclic aromatic hydrocarbons, which make up Coal Tar, are photosensitizers and cause phototoxicity by an oxygen-dependent mechanism. A retrospective study of the reproductive toxicity of Coal Tar in humans compared exposed women to controls and found little difference in spontaneous abortion and congenital disorders. Cancer epidemiology studies of patients who have received Coal Tar therapy of one form or other have failed to link treatment with an increase in the risk of cancer. Although the Cosmetic Ingredient Review (CIR) Expert Panel believes that Coal Tar use as an antidandruff ingredient in OTC drug preparations is adequately addressed by the FDA regulations, the Panel also believes that the appropriate concentration of use of Coal Tar in cosmetic formulations should be that level that does not have a biological effect in the user. Additional data needed to make a safety assessment include product types in which Coal Tar is used (other than as an OTC drug ingredient), use concentrations, and the maximum concentration that does not induce a biological effect in users.

PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner.

PubMed

Jiang, H; Lu, H; Schiltz, R L; Pise-Masison, C A; Ogryzko, V V; Nakatani, Y; Brady, J N

1999-12-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat.

PCAF Interacts with Tax and Stimulates Tax Transactivation in a Histone Acetyltransferase-Independent Manner

PubMed Central

Jiang, Hua; Lu, Hanxin; Schiltz, R. Louis; Pise-Masison, Cynthia A.; Ogryzko, Vasily V.; Nakatani, Yoshihiro; Brady, John N.

1999-01-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat. PMID:10567539

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebi, Masahide; Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp; Shimura, Takaya

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cellmore » growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF{beta} enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells. Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGF{beta} might be an important pathway of gastric cancer cell proliferation by TGF{beta}.« less

Cold Preparation of Heroin in a Black Tar Market.

PubMed

Roth, Alexis M; Armenta, Richard F; Wagner, Karla D; Strathdee, Steffanie A; Goldshear, Jesse L; Cuevas-Mota, Jazmine; Garfein, Richard S

2017-07-29

Black tar heroin is typically prepared for injection with heat which decreases the risk of HIV transmission by inactivating the virus. We received reports that persons who inject drugs (PWID) in Tijuana, Baja California, Mexico, a black tar heroin market, were using only water to dissolve heroin. Because Tijuana abuts San Diego County, CA, United States, we undertook the present analyses to determine the prevalence of this practice among PWID in San Diego, California. PWID completed quarterly behavioral assessments and serological testing for blood-borne viruses. Bivariate and multivariable logistic regression models were constructed to assess for individual, social, and structural correlates of preparing heroin without heat within the preceding 6 months. Nearly half of black tar heroin users (149/305) reported they had prepared heroin without heat within 6 months. In multivariable analysis, cold preparation was independently associated with younger age (10 year decrease; AOR = 1.25; 95% CI 1.03, 1.53), more drug injecting acquaintances (per 5 acquaintance increase; AOR = 1.05; 95% CI 1.01, 1.09) and prefilled syringe use (injecting drugs from syringes that are already filled with drugs before purchase; AOR = 1.86; 95% CI 1.14, 3.02). Conclusions/Importance: To our knowledge, this is the first paper to report that PWID living in a black tar heroin market are preparing heroin without heat. Additional research is needed to determine whether this is an endemic practice or PWID are engaging in new forms of drug preparation in response to changes in the environment.

The morphology of transverse aeolian ridges on Mars

NASA Astrophysics Data System (ADS)

Geissler, Paul E.; Wilgus, Justin T.

2017-06-01

A preliminary survey of publicly released high resolution digital terrain models (DTMs) produced by the High Resolution Imaging Science Experiment (HiRISE) camera on Mars Reconnaissance Orbiter identified transverse aeolian ridges (TARs) in 154 DTMs in latitudes from 50°S to 40°N. Consistent with previous surveys, the TARs identified in HiRISE DTMs are found at all elevations, irrespective of the regional thermal inertia of the surface. Ten DTMs were selected for measuring the characteristics of the TARs, including maximum height, mean height, mean spacing (wavelength), and the slope of the surface where they are located. We confined our measurements to features that were taller than 1 m and spaced more than 10 m apart. We found a surprisingly wide variability of TAR sizes within each local region (typically 5 km by 25 km), with up to a factor of 7 difference in TAR wavelengths in a single DTM. The TAR wavelengths do not appear to be correlated to latitude or elevation, but the largest TARs in our small survey were found at lower elevations. The tallest TARs we measured were on the flat floor of Moni crater, within Kaiser crater in the southern highlands. These TARs are up to 14 m tall, with a typical wavelength of 120 m. TAR heights are weakly correlated with their wavelengths. The height-to-wavelength ratios for most TARs are far less than 1/2π (the maximum predicted for antidunes), however in two cases the ratio is close to 1/2π, and in one case (in the bend of a channel) the ratio exceeds 1/2π. TAR wavelengths are uncorrelated with surface slope, both on local and regional scales. TAR heights are weakly anti-correlated with local slope. These results help constrain models of TAR formation, particularly a new hypothesis (Geissler, 2014) that suggests that TARs were formed from micron-sized dust that was transported in suspension. The lack of correlation between TAR wavelength and surface slope seems to rule out formation by gravity-driven dust flows such as avalanches or density currents, and suggests that the TARs were instead produced by the Martian winds.

Multiple transcriptional regulatory domains in the human immunodeficiency virus type 1 long terminal repeat are involved in basal and E1A/E1B-induced promoter activity.

PubMed Central

Kliewer, S; Garcia, J; Pearson, L; Soultanakis, E; Dasgupta, A; Gaynor, R

1989-01-01

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) is the site of activation of the HIV tat protein. However, additional transactivators, such as the adenovirus E1A and herpesvirus ICPO proteins, have also been shown to be capable of activating the HIV LTR. Analysis of adenovirus mutants indicated that complete transactivation of the HIV LTR was dependent on both the E1A and E1B proteins. To determine which regions of the HIV LTR were important for complete E1A/E1B activation, a variety of oligonucleotide-directed mutations in HIV transcriptional regulatory domains were assayed both in vivo and in vitro. S1 nuclease analysis of RNA prepared after transfection of these HIV constructs into HeLa cells infected with wild-type adenovirus indicated that the enhancer, SP1, TATA, and a portion of the transactivation-responsive element were each required for complete E1A/E1B-mediated activation of the HIV LTR. These same promoter elements were required for both basal and E1A/E1B-induced levels of transcription in in vitro transcription reactions performed with cellular extracts prepared from cells infected with dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. No mutations were found that reduced only E1A/E1B-induced expression without proportionally reducing basal levels of transcription, suggesting that E1A/E1B-mediated induction of the HIV LTR requires multiple promoter elements which are also required for basal transcriptional levels. Unlike activation by the tat protein, there was not a rigid dependence on maintenance of the transactivation-responsive stem base pairing for E1A/E1B-mediated activation either in vivo or in vitro, indicating that activation occurs by a mechanism distinct from that of tat induction. Images PMID:2529378

Identification of Essential Genetic Baculoviral Elements for Recombinant Protein Expression by Transactivation in Sf21 Insect Cells.

PubMed

Bleckmann, Maren; Schürig, Margitta; Chen, Fang-Fang; Yen, Zen-Zen; Lindemann, Nils; Meyer, Steffen; Spehr, Johannes; van den Heuvel, Joop

2016-01-01

The Baculovirus Expression Vector System (BEVS) is widely used to produce high amounts of recombinant proteins. Nevertheless, generating recombinant baculovirus in high quality is rather time-consuming and labor-intensive. Alternatively, virus-free expression in insect cells did not achieve similar expression levels for most proteins so far. The transactivation method is a promising approach for protein expression in Sf21 cells. It combines advantages of BEVS and plasmid-based expression by activating strong virus-dependent promoters on a transfected plasmid by baculoviral coinfection. Here, we identified expression elements required for transactivation. Therefore, we designed several vectors comprising different viral promoters or promoter combinations and tested them for eGFP expression using the automated BioLector microcultivation system. Remarkably, only the combination of the very late promoter p10 together with the homologous region 5 (hr5) could boost expression during transactivation. Other elements, like p10 alone or the late viral promoter polH, did not respond to transactivation. A new combination of hr5 and p10 with the strongest immediate early OpMNPV viral promoter OpIE2 improved the yield of eGFP by ~25% in comparison to the previous applied hr5-IE1-p10 expression cassette. Furthermore, we observed a strong influence of the transcription termination sequence and vector backbone on the level of expression. Finally, the expression levels for transactivation, BEVS and solely plasmid-based expression were compared for the marker protein eGFP, underlining the potential of transactivation for fast recombinant protein expression in Sf21 cells. In conclusion, essential elements for transactivation could be identified. The optimal elements were applied to generate an improved vector applicable in virus-free plasmid-based expression, transactivation and BEVS.

Transverse Aeolian Ridges (TARs) on Mars II: Distributions, orientations, and ages

NASA Astrophysics Data System (ADS)

Berman, Daniel C.; Balme, Matthew R.; Rafkin, Scot C. R.; Zimbelman, James R.

2011-05-01

Transverse Aeolian Ridges (TARs), 10 m scale, ripple-like aeolian bedforms with simple morphology, are widespread on Mars but it is unknown what role they play in Mars' wider sediment cycle. We present the results of a survey of all Mars Global Surveyor Narrow angle images in a pole-to-pole study area, 45° longitude wide. Following on from the classification scheme and preliminary surveys of Balme et al. (Balme, M.R., Berman, D.C., Bourke, M.C., Zimbelman, J.R. [2008a]. Geomorphology 101, 703-720) and Wilson and Zimbelman (Wilson, S.A., Zimbelman, J.R. [2004]. J. Geophys. Res. 109 (E10). doi: 10.1029/2004JE002247) we searched more than 10,000 images, and found that over 2000 reveal at least 5% areal cover by TARs. The mean TAR areal cover in the study area is about 7% (3% in the northern hemisphere and 11% in the southern hemisphere) but TARs are not homogenously distributed - they are concentrated in the mid-low latitudes and almost absent poleward of 35°N and 55°S. We found no clear correlation between TAR distribution and any of thermal inertia, kilometer-scale roughness, or elevation. We did find that TARs are less common at extremes of elevation. We found that TARs are most common near the equator (especially in the vicinity of Meridiani Planum, in which area they have a distinctive "barchan-like" morphology) and in large southern-hemisphere impact craters. TARs in the equatorial band are usually associated with outcrops of layered terrain or steep slopes, hence their relative absence in the northern hemisphere. TARs in the southern hemisphere are most commonly associated with low albedo, intercrater dune fields. We speculate that the mid-latitude mantling terrain (e.g., Mustard, J.F., Cooper, C.D., Rifkin, M.K. [2001]. Nature 412, 411-414; Kreslavsky, M.A., Head, J.W. [2002]. J. Geophys. Res. 29 (15). doi: 10.1029/2002GL015392) could also play a role in covering TARs or inhibiting saltation. We compared TAR distribution with general circulation model (GCM) climate data for both surface wind shear stress and wind direction. We performed GCM runs at various obliquity values to simulate the effects of changing obliquity on recent Mars climate. We found good general agreement between TAR orientation and GCM wind directions from present day obliquity conditions in many cases, but found no good correlation between wind shear stress and TAR distribution. We performed preliminary high resolution crater count studies of TARs in both equatorial and southern intracrater dunefield settings and compared these to superposition relationships between TARs and large dark dunes. Our results show that TARs near dunefield appear to be younger than TARs in the equatorial regions. We infer that active saltation from the large dunes keeps TARs active, but that TARs are not active under present day condition when distal to large dunes - perhaps supporting the interpretation that TARs are granule ripples. We conclude that local geology, rather than wind strength, controls TAR distribution, but that their orientation matches present-day regional wind patterns in most cases. We suggest that TARs are likely most (perhaps only) active today when they are proximal to large dark dune fields.

Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar and menthol for over-the-counter human use; amendment to the monograph. Final rule

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2006-03-15

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and psoriasis drug products to include the combination of 1.8 percent coal tar solution and 1.5 percent menthol in a shampoo drug product to control dandruff. FDA did not receive any comments or data in response to its previously proposed rule to include this combination. This final rule is part of FDA's ongoing review of OTC drug products.

A case study on effects of oil spills and tar-ball pollution on beaches of Goa (India).

PubMed

Rekadwad, Bhagwan N; Khobragade, Chandrahasya N

2015-11-15

This paper reports the impact of oil spills and tar-ball pollution on the coastal ecosystem of Goa. The factors responsible for degrading the marine ecosystem of the Goan coastline are analyzed. Uncontrolled activities were found to degrade the marine and coastal biodiversity, in turn polluting all beaches. This had a direct impact on the Goan economy through a decline in tourism. The government must adopt the necessary control measures to restore Goan beaches and the surrounding coastal areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques.

PubMed Central

Viglianti, G A; Rubinstein, E P; Graves, K L

1992-01-01

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions. Images PMID:1629957

Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3Kδ/Akt and NFκB induction in a murine asthma model.

PubMed

El-Hashim, Ahmed Z; Khajah, Maitham A; Renno, Waleed M; Babyson, Rhema S; Uddin, Mohib; Benter, Ibrahim F; Ezeamuzie, Charles; Akhtar, Saghir

2017-08-30

The molecular mechanisms underlying asthma pathogenesis are poorly characterized. In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kδ/Akt and NF-κB are signaling effectors downstream of Src/EGFR activation; and (3) if upstream inhibition of Src/EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways. Allergic inflammation resulted in increased phosphorylation of EGFR, Akt, ERK1/2 and IκB in the lung tissues from ovalbumin (OVA)-challenged BALB/c mice. Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness. Treatment with pathway-selective inhibitors for ERK1/2 (PD89059) and PI3Kδ/Akt (IC-87114) respectively, or an inhibitor of NF-κB (BAY11-7085) also reduced the OVA-induced asthmatic phenotype but to a lesser extent compared to Src/EGFR inhibition. Thus, Src via EGFR transactivation and subsequent downstream activation of multiple pathways regulates the allergic airway inflammatory response. Furthermore, a broader upstream inhibition of Src/EGFR offers an attractive therapeutic alternative in the treatment of asthma relative to selectively targeting the individual downstream signaling effectors.

In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax.

PubMed

Paca-Uccaralertkun, S; Zhao, L J; Adya, N; Cross, J V; Cullen, B R; Boros, I M; Giam, C Z

1994-01-01

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.

The TAR effect: when the ones who dislike become the ones who are disliked.

PubMed

Gawronski, Bertram; Walther, Eva

2008-09-01

Four studies tested whether a source's evaluations of other individuals can recursively transfer to the source, such that people who like others acquire a positive valence, whereas people who dislike others acquire a negative valence (Transfer of Attitudes Recursively; TAR). Experiment 1 provides first evidence for TAR effects, showing recursive transfers of evaluations regardless of whether participants did or did not have prior knowledge about the (dis)liking source. Experiment 2 shows that previously but not subsequently acquired knowledge about targets that were (dis)liked by a source overrode TAR effects in a manner consistent with cognitive balance. Finally, Experiments 3 and 4 demonstrate that TAR effects are mediated by higher order propositional inferences (in contrast to lower order associative processes), in that TAR effects on implicit attitude measures were fully mediated by TAR effects on explicit attitude measures. Commonalities and differences between the TAR effect and previously established phenomena are discussed.

Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

PubMed

Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

2016-01-04

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

Insights into the mechanisms of RNA secondary structure destabilization by the HIV-1 nucleocapsid protein.

PubMed

Belfetmi, Anissa; Zargarian, Loussiné; Tisné, Carine; Sleiman, Dona; Morellet, Nelly; Lescop, Ewen; Maskri, Ouerdia; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

2016-04-01

The mature HIV-1 nucleocapsid protein NCp7 (NC) plays a key role in reverse transcription facilitating the two obligatory strand transfers. Several properties contribute to its efficient chaperon activity: preferential binding to single-stranded regions, nucleic acid aggregation, helix destabilization, and rapid dissociation from nucleic acids. However, little is known about the relationships between these different properties, which are complicated by the ability of the protein to recognize particular HIV-1 stem-loops, such as SL1, SL2, and SL3, with high affinity and without destabilizing them. These latter properties are important in the context of genome packaging, during which NC is part of the Gag precursor. We used NMR to investigate destabilization of the full-length TAR (trans activating response element) RNA by NC, which is involved in the first strand transfer step of reverse transcription. NC was used at a low protein:nucleotide (nt) ratio of 1:59 in these experiments. NMR data for the imino protons of TAR identified most of the base pairs destabilized by NC. These base pairs were adjacent to the loops in the upper part of the TAR hairpin rather than randomly distributed. Gel retardation assays showed that conversion from the initial TAR-cTAR complex to the fully annealed form occurred much more slowly at the 1:59 ratio than at the higher ratios classically used. Nevertheless, NC significantly accelerated the formation of the initial complex at a ratio of 1:59. © 2016 Belfetmi et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Machine-smoking studies of cigarette filter color to estimate tar yield by visual assessment and through the use of a colorimeter.

PubMed

Morton, Michael J; Williams, David L; Hjorth, Heather B; Smith, Jennifer H

2010-04-01

This paper explores using the intensity of the stain on the end of the filter ("filter color") as a vehicle for estimating cigarette tar yield, both by instrument reading of the filter color and by visual comparison to a template. The correlation of machine-measured tar yield to filter color measured with a colorimeter was reasonably strong and was relatively unaffected by different puff volumes or different tobacco moistures. However, the correlation of filter color to machine-measured nicotine yield was affected by the moisture content of the cigarette. Filter color, as measured by a colorimeter, was generally comparable to filter extraction of either nicotine or solanesol in its correlation to machine-smoked tar yields. It was found that the color of the tar stain changes over time. Panelists could generally correctly order the filters from machine-smoked cigarettes by tar yield using the intensity of the tar stain. However, there was considerable variation in the panelist-to-panelist tar yield estimates. The wide person-to-person variation in tar yield estimates, and other factors discussed in the text could severely limit the usefulness and practicality of this approach for visually estimating the tar yield of machine-smoked cigarettes. Copyright 2009 Elsevier Inc. All rights reserved.

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62.

PubMed

Kim, Seong K; Shakya, Akhalesh K; Kim, Seongman; O'Callaghan, Dennis J

2016-01-15

The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with cellular Mediator 25 in bimolecular complementation assays. The interaction of the IE62 SRT with nucleolar-ribosomal protein EAP resulted in the formation of globular structures within the nucleus. Understanding the mechanisms by which the TAD and SRT of IE62 contribute to the function of this essential regulatory protein is important in understanding the gene program of this human pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62

PubMed Central

Shakya, Akhalesh K.; Kim, Seongman; O'Callaghan, Dennis J.

2015-01-01

ABSTRACT The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. IMPORTANCE The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with cellular Mediator 25 in bimolecular complementation assays. The interaction of the IE62 SRT with nucleolar-ribosomal protein EAP resulted in the formation of globular structures within the nucleus. Understanding the mechanisms by which the TAD and SRT of IE62 contribute to the function of this essential regulatory protein is important in understanding the gene program of this human pathogen. PMID:26537679

Catalytic decomposition of tar derived from wood waste pyrolysis using Indonesian low grade iron ore as catalyst

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wicakso, Doni Rahmat; Chemical Engineering Department, Faculty of Engineering, Gadjah Mada University, Jalan Grafika No. 2 Bulaksumur, Yogyakarta, 55281; Sutijan

Low grade iron ore can be used as an alternative catalyst for bio-tar decomposition. Compared to other catalysts, such as Ni, Rd, Ru, Pd and Pt, iron ore is cheaper. The objective of this research was to investigate the effect of using low grade iron ore as catalyst for tar catalytic decomposition in fixed bed reactor. Tar used in this experiment was pyrolysis product of wood waste while the catalyst was Indonesian low grade iron ore. The variables studied were temperatures between 500 – 600 °C and catalyst weight between 0 – 40 gram. The first step, tar was evaporatedmore » at 450 °C to produce tar vapor. Then, tar vapor was flowed to fixed bed reactor filled low grade iron ore. Gas and tar vapor from reactor was cooled, then the liquid and uncondensable gas were analyzed by GC/MS. The catalyst, after experiment, was weighed to calculate total carbon deposited into catalyst pores. The results showed that the tar components that were heavy and light hydrocarbon were decomposed and cracked within the iron ore pores to from gases, light hydrocarbon (bio-oil) and carbon, thus decreasing content tar in bio-oil and increasing the total gas product. In conclusion, the more low grade iron ore used as catalyst, the tar content in the liquid decrease, the H{sup 2} productivity increased and calorimetric value of bio-oil increased.« less

Autoinflammation Around AES Total Ankle Replacement Implants.

PubMed

Koivu, Helka; Takakubo, Yuya; Mackiewicz, Zygmunt; Al-Samadi, Ahmed; Soininen, Antti; Peled, Nitai; Kukis, Modestas; Trokovic, Nina; Konttinen, Yrjö T

2015-12-01

Failure of total ankle replacement (TAR) can be characterized by early peri-implant osteolysis even in the presence of very modest numbers of wear particles. The hypothesis of the study was that this reaction is in part mediated by autoinflammatory responses mediated via damage-associated molecular patterns (DAMPs, danger signals) and pattern-recognizing danger signal receptors (PRRs). Peri-implant tissue and control samples from 10 patients with AES implants were immunostained for hypoxia inducible factor-1α (HIF-1α), activated caspase-3, high-mobility group box 1 (HMGB1), receptor for advanced glycation end product (RAGE), and toll-like receptors TLR2 and TLR4. Results were evaluated on a 0 to 4 scale (from 0% to >50% stained area). Peri-implant tissue around failed TAR implants had a relatively high mean HIF-1α score of 3 on a scale, which however was similar in control samples. HMGB1 (a DAMP) was seen to be mobilized from nuclei to cellular cytoplasm, and the active caspase-3(+) cells were increased. All PRRs were increased in revision samples. Increased expression of HMGB1 and other danger signals together with increased PRR-dependent responsiveness could contribute to autoinflammatory peri-implantitis, multilocular cyst formation, and osteolysis in failed TAR implants. Level IV, case series. © The Author(s) 2015.

Mortality among workers exposed to coal tar pitch volatiles and welding emissions: an exercise in epidemiologic triage.

PubMed Central

Silverstein, M; Maizlish, N; Park, R; Mirer, F

1985-01-01

The United Automobile Workers International Union has established a system of epidemiologic triage to evaluate patterns of mortality among groups of union members. In response to worker concerns, the Union examined mortality at a metal stamping plant, using a method which linked pension records with the State of Michigan computerized death registry. The observed proportion of malignant neoplasms was nearly twice that expected (95% Confidence Limits 1.36, 2.62). Two- to five-fold excess proportional mortality from cancer of the digestive organs, lung cancer, and leukemia accounted for most of the overall excess. Strong associations were found between lung and digestive organ cancer and employment as maintenance welders or millwrights in the plant (odds ratios greater than 10). High levels of six polycyclic aromatic hydrocarbons with mutagenic and carcinogenic properties were found during hot coal tar application to wood block floors, work conducted by the high-risk groups. These levels were substantially reduced following the purchase of new tar pots. The example demonstrates that epidemiologic tools can play a valuable role in occupational health decision making, but care must be taken to avoid mechanical reliance on quantitative testing and to acknowledge the important role of social and political value judgments in the establishment of responsible public policy. PMID:4051064

Effect of water addition in a microwave assisted thermal cracking of biomass tar gasification

NASA Astrophysics Data System (ADS)

Warsita, A.; Surya, I.

2018-02-01

Producer gas from biomass gasification is plagued by the presence of tar which causes pipe blockages. Thermal and catalytic treatments in a microwave reactor have been shown to be effective methods for removing tar from producer gas. A question arises as to the possibility of enhancing the removal mechanism by adding water into the reactor. Thermal treatment with a various amount of water was added at temperatures in the range of 800-1200°C. The tar removal efficiency obtained 96.32% at the optimum temperature of 1200°C at the water to tar ratio (W/T) of 0.3. This study shows that the removal of tar by microwave irradiation with water addition is a significant and effective method in tar cracking.

Chinese ‘low-tar’ cigarettes do not deliver lower levels of nicotine and carcinogens

PubMed Central

Gan, Quan; Lu, Wei; Xu, Jiying; Li, Xinjian; Goniewicz, Maciej; Benowitz, Neal L

2010-01-01

Background Low-tar cigarette smoking is gaining popularity in China. The China National Tobacco Corporation (CNTC) promotes low-tar cigarettes as safer than regular cigarettes. Methods A total of 543 male smokers smoking cigarettes with different tar yields (15 mg, regular cigarettes, 10–13 mg low-tar cigarettes and <10 mg low-tar cigarettes) were recruited in Shanghai, China, who then completed a questionnaire on smoking behaviour and provided a urine sample for analysis of the nicotine metabolites cotinine and trans-3′-hydroxycotinine. A total of 177 urine samples were selected at random for the analysis of the carcinogens polycyclic aromatic hydrocarbon metabolites (PAHs) (1-hydroxypyrene, naphthols, hydroxyfluorenes and hydroxyphenanthrenes) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK) metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and NNAL-glucuronide. Values were normalised by creatinine to correct for possible distortions introduced by dilution or concentration of the urine. Results Smokers of low-tar cigarettes smoked fewer cigarettes per day (p=0.001) compared to smokers of regular cigarettes. Despite this lower reported consumption, levels of cotinine, trans-3′-hydroxycotinine and PAHs in urine of people smoking low-tar cigarettes were not correlated with nominal tar delivery of the cigarettes they smoked. Urine concentrations of NNAL were higher in smokers of lower tar than higher tar cigarettes. Conclusions Chinese low-tar cigarettes do not deliver lower doses of nicotine and carcinogens than regular cigarettes, therefore it is unlikely that there would be any reduction in harm. CNTC's promotion of low-tar cigarettes as ‘less harmful’ is a violation of the World Health Organization Framework Convention on Tobacco Control, which China ratified in 2005. PMID:20507920

Genus Beta Human Papillomavirus E6 Proteins Vary in Their Effects on the Transactivation of p53 Target Genes

PubMed Central

White, Elizabeth A.; Walther, Johanna; Javanbakht, Hassan

2014-01-01

ABSTRACT The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly in patients with the genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two of the genus beta HPV E6 proteins bind to and/or increase the steady-state levels of p53 in squamous epithelial cells. This is in contrast to a well-characterized ability of the E6 proteins of cancer-associated HPVs of genus alpha HPV, which inactivate p53 by targeting its ubiquitin-mediated proteolysis. In this study, we have investigated the ability of genus beta E6 proteins from eight different HPV types to block the transactivation of p53 target genes following DNA damage. We find that the E6 proteins from diverse beta HPV species and types vary in their capacity to block the induction of MDM2, p21, and proapoptotic genes after genotoxic stress. We conclude that some genus beta HPV E6 proteins inhibit at least some p53 target genes, although perhaps not by the same mechanism or to the same degree as the high-risk genus alpha HPV E6 proteins. IMPORTANCE This study addresses the ability of various human papillomavirus E6 proteins to block the activation of p53-responsive cellular genes following DNA damage in human keratinocytes, the normal host cell for HPVs. The E6 proteins encoded by the high-risk, cancer-associated HPV types of genus alpha HPV have a well-established activity to target p53 degradation and thereby inhibit the response to DNA damage. In this study, we have investigated the ability of genus beta HPV E6 proteins from eight different HPV types to block the ability of p53 to transactivate downstream genes following DNA damage. We find that some, but not all, genus beta HPV E6 proteins can block the transactivation of some p53 target genes. This differential response to DNA damage furthers the understanding of cutaneous HPV biology and may help to explain the potential connection between some beta HPVs and cancer. PMID:24850740

Understanding the stability of pyrolysis tars from biomass in a view point of free radicals.

PubMed

He, Wenjing; Liu, Qingya; Shi, Lei; Liu, Zhenyu; Ci, Donghui; Lievens, Caroline; Guo, Xiaofen; Liu, Muxin

2014-03-01

Fast pyrolysis of biomass has attracted increasing attention worldwide to produce bio-tars that can be upgraded into liquid fuels and chemicals. However, the bio-tars are usually poor in quality and stability and are difficult to be upgraded. To better understand the nature of the bio-tars, this work reveals radical concentration of tars derived from pyrolysis of two kinds of biomass. The tars were obtained by condensing the pyrolysis volatiles in 3s. It shows that the tars contain large amounts of radicals, at a level of 10(16)spins/g, and are able to generate more radicals at temperatures of 573K or higher, reaching a level of 10(19)spins/g at 673K in less than 30min. The radical generation in the tar samples is attributed to the formation of THF insoluble matters (coke), which also contain radicals. The radical concentrations of the aqueous liquids obtained in pyrolysis are also studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pollutant sensitivity of the endangered Tar River Spinymussel as assessed by single chemical and effluent toxicity tests

USGS Publications Warehouse

Augspurger, Thomas P.; Wang, Ning; Kunz, James L.; Ingersoll, Christopher G.

2014-01-01

The federally endangered Tar River spinymussel (Elliptio steinstansana) is endemic to the Tar River and Neuse River systems in North Carolina. The extent to which water quality limits Tar River spinymussels’ recovery is important to establish, and one aspect of that is understanding the species’ pollutant sensitivity. The primary objectives of this study were to 1) develop captive propagation and culture methods for Tar River spinymussels; 2) determine the pollutant sensitivity of captively propagated Tar River spinymussels; 3) examine the utility of the non-endangered yellow lance (Elliptio lanceolata), yellow lampmussel (Lampsilis cariosa) and notched rainbow (Villosa constricta) as surrogates for the Tar River spinymussels’ chemical sensitivity; 4) develop a 7-d method for conducting effluent toxicity tests starting with newly transformed mussels; 5) assess the toxicity of municipal wastewater effluents discharged into the Tar River spinymussels’ current and historic habitat; and, 6) evaluate the protection afforded by existing effluent toxicity test requirements.

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

PubMed Central

Bertazzoni, Umberto; Turci, Marco; Avesani, Francesca; Di Gennaro, Gianfranco; Bidoia, Carlo; Romanelli, Maria Grazia

2011-01-01

Human T-lymphotropic viruses type 1 (HTLV-1) and type 2 (HTLV-2) present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity. PMID:21994745

Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter.

PubMed

Zhuang, Fengfeng; Nguyen, Manuel P; Shuler, Charles; Liu, Yi-Hsin

2009-04-03

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.

Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

PubMed Central

Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

2009-01-01

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and Heat shock factors may play a contributing role. PMID:19338779

EZH2 phosphorylation regulates Tat-induced HIV-1 transactivation via ROS/Akt signaling pathway.

PubMed

Zhang, Hong-Sheng; Liu, Yang; Wu, Tong-Chao; Du, Guang-Yuan; Zhang, Feng-Juan

2015-12-21

EZH2 plays a major role in HIV-1 latency, however, the molecular linkage between Tat-induced HIV-1 transactivation and EZH2 activity is not fully understood. It was shown Tat induced HIV-1 transactivation through inhibiting EZH2 activity. Tat decreased the levels of H3K27me3 and EZH2 occupy at the long terminal repeat (LTR) of HIV-1. We further showed for the first time that transfected with Tat construct resulted in an increase in phosphorylated EZH2 (p-EZH2), mediated by active Akt. ROS/Akt-dependent p-EZH2 was correlated with Tat-induced transactivation. Our study reveals that novel mechanisms allow Tat-induced HIV-1 transactivation by ROS/Akt-dependent downregulating the EZH2 epigenetic silencing machinery. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Tar, nicotine, and carbon monoxide yields of some Nigerian cigarettes.

PubMed Central

Awotedu, A A; Higenbottam, T W; Onadeko, B O

1983-01-01

Fourteen cigarette brands manufactured in Nigeria in 1981 were analysed to determine the tar, nicotine, and carbon monoxide yields. Five of the brands belonged to the high and middle to high tar category (greater than 22 mg/cigarette) and nine to the middle tar (17-22 mg/cigarette) category. None of the cigarettes was in the low to middle and low tar (less than 17 mg/cigarette) category. The nicotine and carbon monoxide yields were similar to those of European cigarettes. Tobacco companies need to manufacture low tar cigarettes in the Third World as is the practice in the economically developed parts of the world. PMID:6619721

Morphology of transverse aeolian ridges (TARs) on Mars from a large sample: Further evidence of a megaripple origin?

NASA Astrophysics Data System (ADS)

Hugenholtz, Chris H.; Barchyn, Thomas E.; Boulding, Adam

2017-04-01

Using HiRISE digital terrain models (DTMs), we developed a large morphological dataset to examine the three-dimensional shape, size, and scaling of Martian transverse aeolian ridges (TARs). Considerable debate exists on the characteristic morphology of TARs and the origins of these enigmatic bedforms. Some researchers suggest polygenesis or multiple classes of similar bedforms. Reliably characterizing the morphology of TARs is an essential prerequisite to developing and evaluating process-based models of TAR genesis and unraveling aeolian processes on the surface of Mars. We present measurements of TAR morphology from a large, DTM-derived dataset (n = 2295). We focused on TARs with 'simple' morphologies in order enable more defensible discretization. Histograms and cumulative log-frequency plots of morphometric parameters (length, width, height, elongation ratio, and wavelength) indicate the sample represents a continuum of bedforms from a single population. A typical TAR from our dataset is 88.5 m long (longest planview axis), 17.3 m wide (shortest planview axis), 1.3 m tall, and has a wavelength of 25.8 m. Combined with these data, the bulk of evidence presented to date suggests that interpreting TARs as megaripples is the most viable working hypothesis.

Study on tar generated from downdraft gasification of oil palm fronds.

PubMed

Atnaw, Samson Mekbib; Kueh, Soo Chuan; Sulaiman, Shaharin Anwar

2014-01-01

One of the most challenging issues concerning the gasification of oil palm fronds (OPF) is the presence of tar and particulates formed during the process considering its high volatile matter content. In this study, a tar sampling train custom built based on standard tar sampling protocols was used to quantify the gravimetric concentration of tar (g/Nm3) in syngas produced from downdraft gasification of OPF. The amount of char, ash, and solid tar produced from the gasification process was measured in order to account for the mass and carbon conversion efficiency. Elemental analysis of the char and solid tar samples was done using ultimate analysis machine, while the relative concentration of the different compounds in the liquid tar was determined making use of a liquid gas chromatography (GC) unit. Average tar concentration of 4.928 g/Nm3 and 1.923 g/Nm3 was obtained for raw gas and cleaned gas samples, respectively. Tar concentration in the raw gas sample was found to be higher compared to results for other biomass materials, which could be attributed to the higher volatile matter percentage of OPF. Average cleaning efficiency of 61% which is comparable to that of sand bed filter and venturi scrubber cleaning systems reported in the literature was obtained for the cleaning system proposed in the current study.

Study on Tar Generated from Downdraft Gasification of Oil Palm Fronds

PubMed Central

Atnaw, Samson Mekbib; Kueh, Soo Chuan; Sulaiman, Shaharin Anwar

2014-01-01

One of the most challenging issues concerning the gasification of oil palm fronds (OPF) is the presence of tar and particulates formed during the process considering its high volatile matter content. In this study, a tar sampling train custom built based on standard tar sampling protocols was used to quantify the gravimetric concentration of tar (g/Nm3) in syngas produced from downdraft gasification of OPF. The amount of char, ash, and solid tar produced from the gasification process was measured in order to account for the mass and carbon conversion efficiency. Elemental analysis of the char and solid tar samples was done using ultimate analysis machine, while the relative concentration of the different compounds in the liquid tar was determined making use of a liquid gas chromatography (GC) unit. Average tar concentration of 4.928 g/Nm3 and 1.923 g/Nm3 was obtained for raw gas and cleaned gas samples, respectively. Tar concentration in the raw gas sample was found to be higher compared to results for other biomass materials, which could be attributed to the higher volatile matter percentage of OPF. Average cleaning efficiency of 61% which is comparable to that of sand bed filter and venturi scrubber cleaning systems reported in the literature was obtained for the cleaning system proposed in the current study. PMID:24526899

7 CFR 3201.76 - Asphalt and tar removers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Asphalt and tar removers. 3201.76 Section 3201.76... Designated Items § 3201.76 Asphalt and tar removers. (a) Definition. Cleaning agents designed to remove asphalt or tar from equipment, roads, or other surfaces. (b) Minimum biobased content. The Federal...

7 CFR 3201.76 - Asphalt and tar removers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Asphalt and tar removers. 3201.76 Section 3201.76... Designated Items § 3201.76 Asphalt and tar removers. (a) Definition. Cleaning agents designed to remove asphalt or tar from equipment, roads, or other surfaces. (b) Minimum biobased content. The Federal...

Thrombin-mediated proteoglycan synthesis utilizes both protein-tyrosine kinase and serine/threonine kinase receptor transactivation in vascular smooth muscle cells.

PubMed

Burch, Micah L; Getachew, Robel; Osman, Narin; Febbraio, Mark A; Little, Peter J

2013-03-08

G protein-coupled receptor signaling is mediated by three main mechanisms of action; these are the classical pathway, β-arrestin scaffold signaling, and the transactivation of protein-tyrosine kinase receptors such as those for EGF and PDGF. Recently, it has been demonstrated that G protein-coupled receptors can also mediate signals via transactivation of serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Atherosclerosis is characterized by the development of lipid-laden plaques in blood vessel walls. Initiation of plaque development occurs via low density lipoprotein retention in the neointima of vessels due to binding with modified proteoglycans secreted by vascular smooth muscle cells. Here we show that transactivation of protein-tyrosine kinase receptors is mediated by matrix metalloproteinase triple membrane bypass signaling. In contrast, serine/threonine kinase receptor transactivation is mediated by a cytoskeletal rearrangement-Rho kinase-integrin system, and both protein-tyrosine kinase and serine/threonine kinase receptor transactivation concomitantly account for the total proteoglycan synthesis stimulated by thrombin in vascular smooth muscle. This work provides evidence of thrombin-mediated proteoglycan synthesis and paves the way for a potential therapeutic target for plaque development and atherosclerosis.

Process for hydrogenation of hydrocarbon tars

DOEpatents

Dolbear, Geoffrey E.

1978-07-18

Hydrocarbon tars of high asphaltene content such as tars obtained from pyrolysis of coal are dissolved in a solvent formed from the hydrogenation of the coal tars, and the resultant mixture hydrogenated in the presence of a catalyst at a pressure from about 1500 to 5000 psig at a temperature from about 500.degree. F to about the critical temperature of the solvent to form a light hydrocarbon as a solvent for the tars. Hydrogen content is at least three times the amount of hydrogen consumed.

Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy.

PubMed

Smith, Nicola J; Chan, Hsiu-Wen; Qian, Hongwei; Bourne, Allison M; Hannan, Katherine M; Warner, Fiona J; Ritchie, Rebecca H; Pearson, Richard B; Hannan, Ross D; Thomas, Walter G

2011-05-01

Major interest surrounds how angiotensin II triggers cardiac hypertrophy via epidermal growth factor receptor transactivation. G protein-mediated transduction, angiotensin type 1 receptor phosphorylation at tyrosine 319, and β-arrestin-dependent scaffolding have been suggested, yet the mechanism remains controversial. We examined these pathways in the most reductionist model of cardiomyocyte growth, neonatal ventricular cardiomyocytes. Analysis with [(32)P]-labeled cardiomyocytes, wild-type and [Y319A] angiotensin type 1 receptor immunoprecipitation and phosphorimaging, phosphopeptide analysis, and antiphosphotyrosine blotting provided no evidence for tyrosine phosphorylation at Y319 or indeed of the receptor, and mutation of Y319 (to A/F) did not prevent either epidermal growth factor receptor transactivation in COS-7 cells or cardiomyocyte hypertrophy. Instead, we demonstrate that transactivation and cardiomyocyte hypertrophy are completely abrogated by loss of G-protein coupling, whereas a constitutively active angiotensin type 1 receptor mutant was sufficient to trigger transactivation and growth in the absence of ligand. These results were supported by the failure of the β-arrestin-biased ligand SII angiotensin II to transactivate epidermal growth factor receptor or promote hypertrophy, whereas a β-arrestin-uncoupled receptor retained these properties. We also found angiotensin II-mediated cardiomyocyte hypertrophy to be attenuated by a disintegrin and metalloprotease inhibition. Thus, G-protein coupling, and not Y319 phosphorylation or β-arrestin scaffolding, is required for epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy via the angiotensin type 1 receptor.

Trace amine-associated receptor 1-Family archetype or iconoclast?

PubMed

Grandy, David K

2007-12-01

Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the "trace amines" (TA) beta-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of 2 publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers Borowsky et al. as TA1 and Bunzow et al. as TA receptor 1 (TAR1). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines, recombinant rodent and human TAR dose-dependently couple to the stimulation of adenosine 3',5'-monophosphate (cAMP) production. Structure-activity profiling based on this functional response has revealed that in addition to the TA, other biologically active compounds containing a 2-carbon aliphatic side chain linking an amino group to at least 1 benzene ring are potent and efficacious TA receptor agonists with amphetamine (AMPH), methamphetamine, 3-iodothyronamine, thyronamine, and dopamine (DA) among the most notable. Almost 100 years after the search for TAR began, numerous TA1/TAR1-related sequences, now called TA-associated receptors (TAAR), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TAR, a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCR. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

Method for filtering solvent and tar sand mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelterborn, J. C.; Stone, R. A.

1985-09-03

A method for filtering spent tar sands from a bitumen and organic solvent solution comprises separating the solution into two streams wherein the bulk of the coarser spent tar sand is in a first stream and has an average particle size of about 10 to about 100 mesh and the bulk of the finer spent tar sand is in a second stream; producing a filter cake by filtering the coarser spent tar sand from the first stream; and filtering the finer spent tar sand from the second stream with the filter cake. The method is particularly useful for filtering solutionsmore » of bitumen extracted from bitumen containing diatomite, spent diatomite and organic solvent.« less

Metal catalysts for steam reforming of tar derived from the gasification of lignocellulosic biomass.

PubMed

Li, Dalin; Tamura, Masazumi; Nakagawa, Yoshinao; Tomishige, Keiichi

2015-02-01

Biomass gasification is one of the most important technologies for the conversion of biomass to electricity, fuels, and chemicals. The main obstacle preventing the commercial application of this technology is the presence of tar in the product gas. Catalytic reforming of tar appears a promising approach to remove tar and supported metal catalysts are among the most effective catalysts. Nevertheless, improvement of catalytic performances including activity, stability, resistance to coke deposition and aggregation of metal particles, as well as catalyst regenerability is greatly needed. This review focuses on the design and catalysis of supported metal catalysts for the removal of tar in the gasification of biomass. The recent development of metal catalysts including Rh, Ni, Co, and their alloys for steam reforming of biomass tar and tar model compounds is introduced. The role of metal species, support materials, promoters, and their interfaces is described. Copyright © 2014 Elsevier Ltd. All rights reserved.

40 CFR 721.10532 - Tar, brown coal.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tar, brown coal. 721.10532 Section 721... Tar, brown coal. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as tar, brown coal (PMN P-12-167, CAS No. 101316-83-0) is subject to...

40 CFR 721.10532 - Tar, brown coal.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tar, brown coal. 721.10532 Section 721... Tar, brown coal. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as tar, brown coal (PMN P-12-167, CAS No. 101316-83-0) is subject to...

Use of mineral oil Fleet enema for the removal of a large tar burn: a case report.

PubMed

Carta, Tricia; Gawaziuk, Justin; Liu, Song; Logsetty, Sarvesh

2015-03-01

Extensive hot tar burns are relatively uncommon. Management of these burns provides a significant clinical challenge especially with respect to tar removal involving a large total body surface area (TBSA), without causing further tissue injury. We report a case of an over 40-year old male construction worker who was removing a malfunctioning cap from broken valve. This resulted in tar spraying over the anterior surface of his body including legs, feet, chest, abdomen, arms, face and oral cavity (80% TBSA covered in tar resulting in a 50% TBSA burn injury). Initially, petrolatum-based, double antibiotic ointment was used to remove the tar, based on our previous experience with small tar burns. However, this was time-consuming and ineffective. The tar was easily removed with mineral oil without irritation. In order to meet the demand for quantity of mineral oil, the pharmacy suggested using mineral oil Fleet enema (C.B. Fleet Company, Inc., Lynchburg, Virginia, USA). The squeezable bottle and catheter tip facilitated administration of oil into the patient's construction boots and under clothing that was adhered to the patient's skin. Tar removal requires an effective, non-toxic and non-irritating agent. Mineral oil is such an agent. For patients that may present with a large surface area tar burn, using mineral oil Fleet enema is a viable option that facilitates application into difficult areas. Grant Support: The Firefighters' Burn Fund (Manitoba) supported this project. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice

PubMed Central

Kramer, Edgar R.

2015-01-01

Background & Aims The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson’s disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. Methods & Results Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. Conclusion These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases. PMID:26291828

The Auxin Biosynthetic TRYPTOPHAN AMINOTRANSFERASE RELATED TaTAR2.1-3A Increases Grain Yield of Wheat.

PubMed

Shao, An; Ma, Wenying; Zhao, Xueqiang; Hu, Mengyun; He, Xue; Teng, Wan; Li, Hui; Tong, Yiping

2017-08-01

Controlling the major auxin biosynthetic pathway to manipulate auxin content could be a target for genetic engineering of crops with desired traits, but little progress had been made because low or high auxin contents often cause developmental inhibition. Here, we performed a genome-wide analysis of bread wheat ( Triticum aestivum ) to identify the Tryptophan Aminotransferase of Arabidopsis1/Tryptophan Aminotransferase-Related (TAA1/TAR) genes that function in the tryptophan-dependent pathway of auxin biosynthesis. Sequence mining together with gene cloning identified 15 TaTAR genes, among which 12 and three genes were phylogenetically close to Arabidopsis ( Arabidopsis thaliana ) AtTAR2 and AtTAR3, respectively. TaTAR2.1 had the most abundant transcripts in the TaTAR2 genes and was expressed mainly in roots and up-regulated by low nitrogen (N) availability. Knockdown of TaTAR2.1 caused vegetative and reproductive deficiencies and impaired lateral root (LR) growth under both high- and low-N conditions. Overexpressing TaTAR2.1-3A in wheat enhanced LR branching, plant height, spike number, grain yield, and aerial N accumulation under different N supply levels. In addition, overexpressing TaTAR2.1-3A in Arabidopsis elevated auxin accumulation in the primary root tip, LR tip, LR primordia, and cotyledon and hypocotyl and increased primary root length, visible LR number, and shoot fresh weight under high- and low-N conditions. Our results indicate that TaTAR2.1 is critical for wheat growth and also shows potential for genetic engineering to reach the aim of improving the grain yield of wheat. © 2017 American Society of Plant Biologists. All Rights Reserved.

Availability of polycyclic aromatic hydrocarbons from lampblack-impacted soils at former oil-gas plant sites in California, USA.

PubMed

Hong, Lei; Luthy, Richard G

2007-03-01

Lampblack-impacted soils at former oil-gas plant sites in California, USA, were characterized to assess the sorption of polycyclic aromatic hydrocarbons (PAHs) and the concentration-dependent effects of a residual oil tar phase on sorption mechanism and availability of PAHs. Nuclear magnetic resonance spectroscopy demonstrated similar aromaticity for both lampblack carbon and the oil tar phase, with pronounced resonance signals in the range of 100 to 150 ppm. Scanning-electron microscopic images revealed a physically distinct oil tar phase, especially at high concentrations in lampblack, which resulted in an organic-like film structure when lampblack particles became saturated with the oil tar. Sorption experiments were conducted on a series of laboratory-prepared lampblack samples to systematically evaluate influences of an oil tar phase on PAH sorption to lampblack. Results indicate that the sorption of PAHs to lampblack exhibits a competition among sorption phases at low oil tar contents when micro- and mesopores are accessible. When the oil tar content increases to more than 5 to 10% by weight, this tar phase fills small pores, reduces surface area, and dominates PAH sorption on lampblack surface. A new PAH partitioning model, Kd = KLB-C(1 - ftar)alpha + ftarKtar (alpha = empirical exponent), incorporates these effects in which the control of PAH partitioning transits from being dominated by sorption in lampblack (KLB-C) to absorption in oil tar (Ktar), depending on the fraction of tar (ftar). This study illustrates the importance of understanding interactions among PAHs, oil tar, and lampblack for explaining the differences in availability of PAHs among site soils and, consequently, for refining site-specific risk assessment and establishing soil cleanup levels.

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction.

PubMed

Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao

2017-12-01

Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

Anti-inflammatory and PPAR transactivational properties of flavonoids from the roots of Sophora flavescens.

PubMed

Quang, Tran Hong; Ngan, Nguyen Thi Thanh; Minh, Chau Van; Kiem, Phan Van; Tai, Bui Huu; Nhiem, Nguyen Xuan; Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Yang, Seo Young; Kim, Young Ho

2013-09-01

Anti-inflammatory and peroxisome proliferator-activated receptors (PPARs) transactivational effects of nine compounds (1 - 9) from the roots of Sophora flavescens were evaluated using NF-κB-luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)-luciferase, and GAL-4-PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC₅₀ values of 4.0 and 4.4 μM, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose-dependent manner, with EC₅₀ values ranging from 1.1 to 13.0 μM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose-dependent PPARα transactivational activity, with EC₅₀ values in a range of 0.9 - 16.0 μM. Compounds 1, 3, 8, and 9 also significantly upregulated PPARγ activity in a dose-dependent manner, with EC₅₀ values of 10.5, 6.6, 15.7, and 1.6 μM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARβ(δ) effects with EC₅₀ values of 11.4, 10.3, and 1.5 μM, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases. Copyright © 2012 John Wiley & Sons, Ltd.

Identification of sources of tar balls deposited along the Southwest Caspian Coast, Iran using fingerprinting techniques.

PubMed

Shirneshan, Golshan; Bakhtiari, Alireza Riyahi; Memariani, Mahmoud

2016-10-15

In 2012, a significant number of tar balls occurred along the Southwest coasts of the Caspian Sea (Iran). Several oil fields of Turkmenistan, Azerbaijan and Iran might be sources of oil spills and lead to the formation of these tar balls. For source identification, 6 tar ball samples were collected from the Southwest beaches of the Caspian Sea and subjected to fingerprint analysis based on the distribution of the source-specific biomarkers of pentacyclic tri-terpanes and steranes. Comparing the diagenic ratios revealed that the tar balls were chemically similar and originated from the same source. Results of double ratio plots (e.g., C29/C30 versus ∑C31-C35/C30 and C28 αββ/(C27 αββ+C29 αββ) versus C29 αββ/(C27 αββ+C28 αββ)) in the tar balls and oils from Iran, Turkmenistan and Azerbaijan indicated that the tar balls might be the result of spills from Turkmenistan oil. Moreover, principle component analysis (PCA) using biomarker ratios on the tar balls and 20 crude oil samples from different wells of Azerbaijan, Iran and Turkmenistan oils showed that the tar balls collected at the Southwest beaches are highly similar to the Turkmenistan oil but one of the Azerbaijan oils (from Bahar field oils) was found to be also slightly close to the tar balls. The weathering characterizations based on the presence of UCM (unresolved complex mixture) and low/high molecular weight ratios (L/H) of alkanes and PAHs indicated the tar ball samples have been significantly influenced by natural weathering processes such as evaporation, photo-degradation and biodegradation. This is the first study of its kind in Iran to use fingerprinting for source identification of tar balls. Copyright © 2016 Elsevier B.V. All rights reserved.

Transverse Aeolian Ridges on Mars: Sediment sources, volumes, and ages.

NASA Astrophysics Data System (ADS)

Berman, D. C.; Balme, M. R.

2014-12-01

Transverse Aeolian Ridges (TARs) are aeolian bedforms that are morphologically and dimensionally distinct from Large Dark Dune (LDD) fields, being generally brighter than, or of similar albedo to, the surrounding terrain. These features are significantly smaller than the LDDs, appear to form normal to local winds, and tend to have simple, transverse, ripple-like morphologies. Whether these small martian bedforms represent large granule ripples, small transverse dunes, or something else entirely is currently under debate. The spatial distribution of TARs provides important information about where on Mars aeolian sediments are concentrated, and determining their volume can help us constrain the sediment transport regime on Mars. Also, if we can determine if TARs were active only in the past, or whether TARs are mobile under today's wind conditions, then we can begin to assess when and where TARs are/were active over Mars' recent geological history. Thus TARs have the potential for being indicators/records of climate change on Mars. In this work we build on previous work [1,2] and focus on the local/regional scale. We have identified six regional study areas, each 5° by 5°, to investigate the behavior of TARs in detail; one in the northern hemisphere, three in the equatorial band, and two in the southern hemisphere. We have systematically mapped TAR and LDD deposits in each study area to constrain sediment transport pathways and identify sediment sources. In general, TAR sediments appear to be tied to local sources such as LDDs or layered terrains. HiRISE DTMs were utilized to measure TAR heights, widths, wavelengths, and lengths to calculate sediment volumes and estimate volumes over entire study areas based on mapping. Crater count analyses on contiguous TAR fields in the equatorial regions, where the bedforms appear more lithified, reveal ages of several million years. Mid-latitude TAR fields do not show any superposed craters, suggesting much younger deposits. References: [1] Balme, M.R., D.C. Berman, M.C. Bourke, and J.R. Zimbelman, Transverse Aeolian Ridges (TARs) on Mars, Geomorphology, 101, 703-720, 2008. [2] Berman, D.C., M.R. Balme, S. Rafkin, and J.R. Zimbelman, Transverse Aeolian Ridges (TARs) on Mars II: Distributions, orientations, and ages, Icarus 213, 116-130, 2011

The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter.

PubMed

Hoffmeister, Albrecht; Ropolo, Alejandro; Vasseur, Sophie; Mallo, Gustavo V; Bodeker, Hans; Ritz-Laser, Beate; Dressler, Gregory R; Vaccaro, Maria Ines; Dagorn, Jean-Charles; Moreno, Silvia; Iovanna, Juan Lucio

2002-06-21

p8 is a nuclear DNA-binding protein, which was identified because its expression is strongly activated in response to several stresses. Biochemical and biophysical studies revealed that despite a weak sequence homology p8 is an HMG-I/Y-like protein, suggesting that p8 may be involved in transcription regulation. Results reported here strongly support this hypothesis. Using a pull-down approach, we found that p8 interacts with the general co-activator p300. We also found that, similar to the HMG proteins, p300 was able to acetylate recombinant p8 in vitro, although the significance of such modification remains to be determined. Then a screening by the two-hybrid system, using p8 as bait, allowed us to identify the Pax2 trans-activation domain-interacting protein (PTIP) as another partner of p8. Transient transfection studies revealed that PTIP is a strong inhibitor of the trans-activation activities of Pax2A and Pax2B on the glucagon gene promoter, which was chosen as a model because it is a target of the Pax2A and Pax2B transcription factors. This effect is completely abolished by co-transfection of p8 in glucagon-producing InRIG9 cells, indicating that p8 binding to PTIP prevents inhibition of the glucagon gene promoter. This was not observed in NIH3T3 fibroblasts that do not express glucagon. Finally, expression of p8 enhances the effect of p300 on Pax2A and Pax2B trans-activation of the glucagon gene promoter. These observations suggest that in glucagon-producing cells p8 is a positive cofactor of the activation of the glucagon gene promoter by Pax2A and Pax2B, both by recruiting the p300 cofactor to increase the Pax2A and Pax2B activities and by binding the Pax2-interacting protein PTIP to suppress its inhibition.

Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanao-Hamai, Michiko; Son, Bo-Kyung; Institute of Gerontology, The University of Tokyo, Tokyo

Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth musclemore » cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2 inhibits Pi-induced apoptosis by restoration of Gas6-mediated survival pathway. • Gas6 transactivation by E2 is mediated by ERα.« less

29 CFR 1910.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 6 2013-07-01 2013-07-01 false Coal tar pitch volatiles; interpretation of term. 1910.1002... Hazardous Substances § 1910.1002 Coal tar pitch volatiles; interpretation of term. As used in § 1910.1000 (Table Z-1), coal tar pitch volatiles include the fused polycyclic hydrocarbons which volatilize from the...

29 CFR 1910.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 6 2010-07-01 2010-07-01 false Coal tar pitch volatiles; interpretation of term. 1910.1002... Hazardous Substances § 1910.1002 Coal tar pitch volatiles; interpretation of term. As used in § 1910.1000 (Table Z-1), coal tar pitch volatiles include the fused polycyclic hydrocarbons which volatilize from the...

29 CFR 1910.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 6 2011-07-01 2011-07-01 false Coal tar pitch volatiles; interpretation of term. 1910.1002... Hazardous Substances § 1910.1002 Coal tar pitch volatiles; interpretation of term. As used in § 1910.1000 (Table Z-1), coal tar pitch volatiles include the fused polycyclic hydrocarbons which volatilize from the...

29 CFR 1910.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 6 2012-07-01 2012-07-01 false Coal tar pitch volatiles; interpretation of term. 1910.1002... Hazardous Substances § 1910.1002 Coal tar pitch volatiles; interpretation of term. As used in § 1910.1000 (Table Z-1), coal tar pitch volatiles include the fused polycyclic hydrocarbons which volatilize from the...

29 CFR 1910.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 6 2014-07-01 2013-07-01 true Coal tar pitch volatiles; interpretation of term. 1910.1002... Hazardous Substances § 1910.1002 Coal tar pitch volatiles; interpretation of term. As used in § 1910.1000 (Table Z-1), coal tar pitch volatiles include the fused polycyclic hydrocarbons which volatilize from the...

16 CFR 802.3 - Acquisitions of carbon-based mineral reserves.

Code of Federal Regulations, 2014 CFR

2014-01-01

... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands together with... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands and associated... pipeline and pipeline system or processing facility which transports or processes oil and gas after it...

16 CFR 802.3 - Acquisitions of carbon-based mineral reserves.

Code of Federal Regulations, 2010 CFR

2010-01-01

... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands together with... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands and associated... pipeline and pipeline system or processing facility which transports or processes oil and gas after it...

16 CFR 802.3 - Acquisitions of carbon-based mineral reserves.

Code of Federal Regulations, 2013 CFR

2013-01-01

... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands together with... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands and associated... pipeline and pipeline system or processing facility which transports or processes oil and gas after it...

16 CFR 802.3 - Acquisitions of carbon-based mineral reserves.

Code of Federal Regulations, 2012 CFR

2012-01-01

... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands together with... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands and associated... pipeline and pipeline system or processing facility which transports or processes oil and gas after it...

16 CFR 802.3 - Acquisitions of carbon-based mineral reserves.

Code of Federal Regulations, 2011 CFR

2011-01-01

... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands together with... gas, shale or tar sands, or rights to reserves of oil, natural gas, shale or tar sands and associated... pipeline and pipeline system or processing facility which transports or processes oil and gas after it...

Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

PubMed

Hossain, Ekhtear; Anand-Srivastava, Madhu B

2017-08-01

We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway.

PubMed

Toubiana, Julie; Rossi, Anne-Lise; Belaidouni, Nadia; Grimaldi, David; Pene, Frederic; Chafey, Philippe; Comba, Béatrice; Camoin, Luc; Bismuth, Georges; Claessens, Yann-Erick; Mira, Jean-Paul; Chiche, Jean-Daniel

2015-10-01

TLR2 has a prominent role in host defense against a wide variety of pathogens. Stimulation of TLR2 triggers MyD88-dependent signaling to induce NF-κB translocation, and activates a Rac1-PI 3-kinase dependent pathway that leads to transactivation of NF-κB through phosphorylation of the P65 NF-κB subunit. This transactivation pathway involves tyrosine phosphorylations. The role of the tyrosine kinases in TLR signaling is controversial, with discrepancies between studies using only chemical inhibitors and knockout mice. Here, we show the involvement of the tyrosine-kinase Lyn in TLR2-dependent activation of NF-κB in human cellular models, by using complementary inhibition strategies. Stimulation of TLR2 induces the formation of an activation cluster involving TLR2, CD14, PI 3-kinase and Lyn, and leads to the activation of AKT. Lyn-dependent phosphorylation of the p110 catalytic subunit of PI 3-kinase is essential to the control of PI 3-kinase biological activity upstream of AKT and thereby to the transactivation of NF-κB. Thus, Lyn kinase activity is crucial in TLR2-mediated activation of the innate immune response in human mononuclear cells. © The Author(s) 2015.

Proteolytic turnover of the Gal4 transcription factor is not required for function in vivo.

PubMed

Nalley, Kip; Johnston, Stephen Albert; Kodadek, Thomas

2006-08-31

Transactivator-promoter complexes are essential intermediates in the activation of eukaryotic gene expression. Recent studies of these complexes have shown that some are quite dynamic in living cells owing to rapid and reversible disruption of activator-promoter complexes by molecular chaperones, or a slower, ubiquitin-proteasome-pathway-mediated turnover of DNA-bound activator. These mechanisms may act to ensure continued responsiveness of activators to signalling cascades by limiting the lifetime of the active protein-DNA complex. Furthermore, the potency of some activators is compromised by proteasome inhibition, leading to the suggestion that periodic clearance of activators from a promoter is essential for high-level expression. Here we describe a variant of the chromatin immunoprecipitation assay that has allowed direct observation of the kinetic stability of native Gal4-promoter complexes in yeast. Under non-inducing conditions, the complex is dynamic, but on induction the Gal4-promoter complexes 'lock in' and exhibit long half-lives. Inhibition of proteasome-mediated proteolysis had little or no effect on Gal4-mediated gene expression. These studies, combined with earlier data, show that the lifetimes of different transactivator-promoter complexes in vivo can vary widely and that proteasome-mediated turnover is not a general requirement for transactivator function.

Biomass Burning Research Using DOE ARM Single-Particle Soot Photometer (SP2) Field Campaign Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onasch, Timothy B; Sedlacek, Arthur J; Lewis, Ernie

The focus of this laboratory study was to investigate the chemical and optical properties, and the detection efficiencies, of tar balls generated in the laboratory using the same instruments deployed on the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility Gulfstream-1 (G-1) aircraft during the 2013 Biomass Burning Observation Project (BBOP) field study, during which tar balls were observed in wildland biomass burning particulate emissions. Key goals of this laboratory study were: (a) measuring the chemical composition of tar balls to provide insights into the atmospheric processes that form (evaporation/oxidation) and modify them in biomass burningmore » plumes, (b) identifying whether tar balls contain refractory black carbon, (c) determining the collection efficiencies of tar balls impacting on the 600oC heated tungsten vaporizer in the Aerodyne Soot Particle Aerosol Mass Spectrometer (SP-AMS) (i.e., given the observed low volatilities, AMS measurements might underestimate organic biomass burning plume loadings), and (d) measuring the wavelength-dependent, mass-specific absorption cross-sections of brown carbon components of tar balls. This project was funded primarily by the DOE Atmospheric System Research (ASR) program, and the ARM Facility made their single-particle soot photometer (SP2) available for September 1-September 31, 2016 in the Aerodyne laboratories. The ARM mentor (Dr. Sedlacek) requested no funds for mentorship or data reduction. All ARM SP2 data collected as part of this project are archived in the ARM Data Archive in accordance with established protocols. The main objectives of the ARM Biomass Burning Observation Period (BBOP, July-October, 2013) field campaign were to (1) assess the impact of wildland fires in the Pacific Northwest on climate, through near-field and regional intensive measurement campaigns, and (2) investigate agricultural burns to determine how those biomass burn plumes differ from those from wildland fires. During BBOP, tar balls, small solid particles of organic substances, were observed downwind from wildland fires (at plume ages of 0-3 hours), but not agricultural burns. Observations of the tar balls on transmission electron microscope (TEM) grids suggest that they formed during atmospheric transport, likely due to the same atmospheric processes that increased the oxidation levels of the organic aerosol. Preliminary analyses suggest that tar balls may account for almost 50% of the total particle number, and 30% of the total organic particle mass, of the aerosol emitted from the burning events. These BBOP observations are described in detail in a manuscript in preparation (Sedlacek et al., 2017). The current laboratory study lasted four weeks and was conducted in the aerosol laboratories located at Aerodyne Research, Inc. in Billerica, Massachusetts. Tar balls were generated from several different biomass fuels, including samples from BBOP-related field sites, following literature procedures (Hoffer, Tóth, Nyirö-Kósa, Pósfai, and Gelencsér, 2016; Tóth, Hoffer, Nyirö-Kósa, Pósfai, and Gelencsér, 2014), and they were characterized using the same equipment used during the 2013 BBOP study, specifically the SP-AMS, SP2 and TEM. This study determined that laboratory-generated tar balls (1) are refractory with respect to TEM analysis in a similar manner to those collected during BBOP from wildland fires, (2) are composed of organic material with some refractory carbon components, (3) can be measured quantitatively by the SP-AMS, strengthening observations during BBOP, (4) absorb visible light, and (4) are dominated by unsaturated hydrocarbons that may be responsible for their light-absorbing properties. The results from this project are already being incorporated into our analysis of the formation processes and emission rates of tar balls as a function of fuel and combustion conditions from wildland fires.« less

Lysine acetylation sites in bovine foamy virus transactivator BTas are important for its DNA binding activity.

PubMed

Chang, Rui; Tan, Juan; Xu, Fengwen; Han, Hongqi; Geng, Yunqi; Li, Yue; Qiao, Wentao

2011-09-15

Cellular acetylation signaling is important for viral gene regulation, particularly during the transactivation of retroviruses. The regulatory protein of bovine foamy virus (BFV), BTas, is a transactivator that augments viral gene transcription from both the long terminal repeat (LTR) promoter and the internal promoter (IP). In this study, we report that the histone acetyltransferase (HAT), p300, specifically acetylates BTas both in vivo and in vitro. Further studies demonstrated that BTas acetylation markedly enhances its transactivation activity. Mutagenesis analysis identified three lysines at positions 66, 109 and 110 in BTas that are acetylated by p300. The K110R mutant lost its binding to BFV promoter as well as its ability to activate BFV promoter. The acetylation of K66 and K109 may contribute to increased BTas binding ability. These results suggest that the p300-acetylated lysines of BTas are important for transactivation of BFV promoters and therefore have an important role in BFV replication. Copyright © 2011 Elsevier Inc. All rights reserved.

Full trans–activation mediated by the immediate–early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence

PubMed Central

Kim, Seong K.; Shakya, Akhalesh K.; O'Callaghan, Dennis J.

2015-01-01

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt −89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). PMID:26541315

Comparison of Multisegmental Foot and Ankle Motion Between Total Ankle Replacement and Ankle Arthrodesis in Adults.

PubMed

Seo, Sang Gyo; Kim, Eo Jin; Lee, Doo Jae; Bae, Kee Jeong; Lee, Kyoung Min; Lee, Dong Yeon

2017-09-01

Total ankle replacement (TAR) and ankle arthrodesis (AA) are usually performed for severe ankle arthritis. We compared postoperative foot segmental motion during gait in patients treated with TAR and AA. Gait analysis was performed in 17 and 7 patients undergoing TAR and AA, respectively. Subjects were evaluated using a 3-dimensional multisegmental foot model with 15 markers. Temporal gait parameters were calculated. The maximum and minimum values and the differences in hallux, forefoot, hindfoot, and arch in 3 planes (sagittal, coronal, transverse) were compared between the 2 groups. One hundred healthy adults were evaluated as a control. Gait speed was faster in the TAR ( P = .028). On analysis of foot and ankle segmental motion, the range of hindfoot sagittal motion was significantly greater in the TAR (15.1 vs 10.2 degrees in AA; P = .004). The main component of motion increase was hindfoot dorsiflexion (12.3 and 8.6 degrees). The range of forefoot sagittal motion was greater in the TAR (9.3 vs 5.8 degrees in AA; P = .004). Maximum ankle power in the TAR (1.16) was significantly higher than 0.32 in AA; P = .008). However, the range of hindfoot and forefoot sagittal motion was decreased in both TAR and AA compared with the control group ( P = .000). Although biomechanical results of TAR and AA were not similar to those in the normal controls, joint motions in the TAR more closely matched normal values. Treatment decision making should involve considerations of the effect of surgery on the adjacent joints. Level III, case-control study.

VAPOR PRESSURES AND HEATS OF VAPORIZATION OF PRIMARY COAL TARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eric M. Suuberg; Vahur Oja

1997-07-01

This project had as its main focus the determination of vapor pressures of coal pyrolysis tars. It involved performing measurements of these vapor pressures and from them, developing vapor pressure correlations suitable for use in advanced pyrolysis models (those models which explicitly account for mass transport limitations). This report is divided into five main chapters. Each chapter is a relatively stand-alone section. Chapter A reviews the general nature of coal tars and gives a summary of existing vapor pressure correlations for coal tars and model compounds. Chapter B summarizes the main experimental approaches for coal tar preparation and characterization whichmore » have been used throughout the project. Chapter C is concerned with the selection of the model compounds for coal pyrolysis tars and reviews the data available to us on the vapor pressures of high boiling point aromatic compounds. This chapter also deals with the question of identifying factors that govern the vapor pressures of coal tar model materials and their mixtures. Chapter D covers the vapor pressures and heats of vaporization of primary cellulose tars. Chapter E discusses the results of the main focus of this study. In summary, this work provides improved understanding of the volatility of coal and cellulose pyrolysis tars. It has resulted in new experimentally verified vapor pressure correlations for use in pyrolysis models. Further research on this topic should aim at developing general vapor pressure correlations for all coal tars, based on their molecular weight together with certain specific chemical characteristics i.e. hydroxyl group content.« less

Interaction between two cis-acting elements, ABRE and DRE, in ABA-dependent expression of Arabidopsis rd29A gene in response to dehydration and high-salinity stresses.

PubMed

Narusaka, Yoshihiro; Nakashima, Kazuo; Shinwari, Zabta K; Sakuma, Yoh; Furihata, Takashi; Abe, Hiroshi; Narusaka, Mari; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2003-04-01

Many abiotic stress-inducible genes contain two cis-acting elements, namely a dehydration-responsive element (DRE; TACCGACAT) and an ABA-responsive element (ABRE; ACGTGG/TC), in their promoter regions. We precisely analyzed the 120 bp promoter region (-174 to -55) of the Arabidopsis rd29A gene whose expression is induced by dehydration, high-salinity, low-temperature, and abscisic acid (ABA) treatments and whose 120 bp promoter region contains the DRE, DRE/CRT-core motif (A/GCCGAC), and ABRE sequences. Deletion and base substitution analyses of this region showed that the DRE-core motif functions as DRE and that the DRE/DRE-core motif could be a coupling element of ABRE. Gel mobility shift assays revealed that DRE-binding proteins (DREB1s/CBFs and DREB2s) bind to both DRE and the DRE-core motif and that ABRE-binding proteins (AREBs/ABFs) bind to ABRE in the 120 bp promoter region. In addition, transactivation experiments using Arabidopsis leaf protoplasts showed that DREBs and AREBs cumulatively transactivate the expression of a GUS reporter gene fused to the 120 bp promoter region of rd29A. These results indicate that DRE and ABRE are interdependent in the ABA-responsive expression of the rd29A gene in response to ABA in Arabidopsis.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

PubMed

Hosoyama, Katsuhiro; Ito, Koki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Akiyama, Masatoshi; Adachi, Osamu; Kawatsu, Satoshi; Sasaki, Konosuke; Suzuki, Marina; Sugawara, Yumi; Shimizu, Yuya; Saiki, Yoshikatsu

2016-09-01

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

21 CFR 740.18 - Coal tar hair dyes posing a risk of cancer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Coal tar hair dyes posing a risk of cancer. 740.18... (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.18 Coal tar hair dyes... coal tar hair dye containing any ingredient listed in paragraph (b) of this section shall bear, in...

Treating tar sands formations with karsted zones

DOEpatents

Vinegar, Harold J.; Karanikas, John Michael

2010-03-09

Methods for treating a tar sands formation are described herein. The tar sands formation may have one or more karsted zones. Methods may include providing heat from one or more heaters to one or more karsted zones of the tar sands formation to mobilize fluids in the formation. At least some of the mobilized fluids may be produced from the formation.

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2014 CFR

2014-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2013 CFR

2013-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2010 CFR

2010-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2011 CFR

2011-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2012 CFR

2012-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

Aviation Turbine Fuels from Tar Sands Bitumen and Heavy Oils. Part 1. Process Analysis.

DTIC Science & Technology

1984-09-01

Uinta Basin .......................too.... 11 b . Asphalt Ridge ........................ 13 c.* Tar Sand Triangle ..... to .. .. . .. .. . 15 e...Estimated ............**..* 7 3 CHARACTERISTICS OF UTAH’S MAJOR TAR SANDS ....... 12 4 UINTA BASIN DEPOSITS ................... *........ 13 *.5 UINTA ...7 UINTA BASIN , UTAH PROPERTIES -SUNNYSIDE ........ 20 8 UINTA BASIN , UTAH PROPERTIES -P. R. SPRINGS . 22 r9 ESTIMATED CALIFORNIA TAR SAND DISTRIBUTION

Modeling the impact of bubbling bed hydrodynamics on tar yield and its fluctuations during biomass fast pyrolysis

DOE PAGES

Xiong, Qingang; Ramirez, Emilio; Pannala, Sreekanth; ...

2015-10-09

The impact of bubbling bed hydrodynamics on temporal variations in the exit tar yield for biomass fast pyrolysis was investigated using computational simulations of an experimental laboratory-scale reactor. A multi-fluid computational fluid dynamics model was employed to simulate the differential conservation equations in the reactor, and this was combined with a multi-component, multi-step pyrolysis kinetics scheme for biomass to account for chemical reactions. The predicted mean tar yields at the reactor exit appear to match corresponding experimental observations. Parametric studies predicted that increasing the fluidization velocity should improve the mean tar yield but increase its temporal variations. Increases in themore » mean tar yield coincide with reducing the diameter of sand particles or increasing the initial sand bed height. However, trends in tar yield variability are more complex than the trends in mean yield. The standard deviation in tar yield reaches a maximum with changes in sand particle size. As a result, the standard deviation in tar yield increases with the increases in initial bed height in freely bubbling state, while reaches a maximum in slugging state.« less

Catalytic Tar Reduction for Assistance in Thermal Conversion of Space Waste for Energy Production

NASA Technical Reports Server (NTRS)

Caraccio, Anne Joan; Devor, Robert William; Hintze, Paul E.; Muscatello, Anthony C.; Nur, Mononita

2014-01-01

The Trash to Gas (TtG) project investigates technologies for converting waste generated during spaceflight into various resources. One of these technologies was gasification, which employed a downdraft reactor designed and manufactured at NASA's Kennedy Space Center (KSC) for the conversion of simulated space trash to carbon dioxide. The carbon dioxide would then be converted to methane for propulsion and water for life support systems. A minor byproduct of gasification includes large hydrocarbons, also known as tars. Tars are unwanted byproducts that add contamination to the product stream, clog the reactor and cause complications in analysis instrumentation. The objective of this research was to perform reduction studies of a mock tar using select catalysts and choose the most effective for primary treatment within the KSC downdraft gasification reactor. Because the KSC reactor is operated at temperatures below typical gasification reactors, this study evaluates catalyst performance below recommended catalytic operating temperatures. The tar reduction experimentation was observed by passing a model tar vapor stream over the catalysts at similar conditions to that of the KSC reactor. Reduction in tar was determined using gas chromatography. Tar reduction efficiency and catalyst performances were evaluated at different temperatures.

Ultrasound assisted, thermally activated persulfate oxidation of coal tar DNAPLs.

PubMed

Peng, Libin; Wang, Li; Hu, Xingting; Wu, Peihui; Wang, Xueqing; Huang, Chumei; Wang, Xiangyang; Deng, Dayi

2016-11-15

The feasibility of ultrasound assisted, thermally activated persulfate for effective oxidation of twenty 2-6 ringed coal tar PAHs in a biphasic tar/water system and a triphasic tar/soil/water system were investigated and established. The results indicate that ultrasonic assistance, persulfate and elevated reaction temperature are all required to achieve effective oxidation of coal tar PAHs, while the heating needed can be provided by ultrasonic induced heating as well. Further kinetic analysis reveals that the oxidation of individual PAH in the biphasic tar/water system follows the first-order kinetics, and individual PAH oxidation rate is primary determined by the mass transfer coefficients, tar/water interfacial areas, the aqueous solubility of individual PAH and its concentration in coal tar. Based on the kinetic analysis and experimental results, the contributions of ultrasound, persulfate and elevated reaction temperature to PAHs oxidation were characterized, and the effects of ultrasonic intensity and oxidant dosage on PAHs oxidation efficiency were investigated. In addition, the results indicate that individual PAH degradability is closely related to its reactivity as well, and the high reactivity of 4-6 ringed PAHs substantially improves their degradability. Copyright © 2016 Elsevier B.V. All rights reserved.

Task 3.9 -- Catalytic tar cracking. Semi-annual report, January 1--June 30, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, B.C.; Timpe, R.C.

1995-12-31

Tar produced in the gasification of coal is deleterious to the operation of downstream equipment including fuel cells, gas turbines, hot-gas stream cleanup filters, and pressure swing adsorption systems. Catalytic cracking of tars to smaller hydrocarbons can be an effective means to remove these tars from gas streams and, in the process, generate useful products, e.g., methane gas, which is crucial to the operation of molten carbonate fuel cells. The objectives of this project are to investigate whether gasification tars can be cracked by synthetic nickel-substituted micamontmorillonite, zeolite, or dolomite material; and whether the tars can be cracked selectively bymore » these catalysts to produce a desired liquid and/or gas stream. Results to date are presented in the cited papers.« less

Transformation-associated recombination (TAR) cloning for genomics studies and synthetic biology

PubMed Central

Kouprina, Natalay; Larionov, Vladimir

2016-01-01

Transformation-associated recombination (TAR) cloning represents a unique tool for isolation and manipulation of large DNA molecules. The technique exploits a high level of homologous recombination in the yeast Sacharomyces cerevisiae. So far, TAR cloning is the only method available to selectively recover chromosomal segments up to 300 kb in length from complex and simple genomes. In addition, TAR cloning allows the assembly and cloning of entire microbe genomes up to several Mb as well as engineering of large metabolic pathways. In this review, we summarize applications of TAR cloning for functional/structural genomics and synthetic biology. PMID:27116033

Integrated Biomass Gasification with Catalytic Partial Oxidation for Selective Tar Conversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lingzhi; Wei, Wei; Manke, Jeff

Biomass gasification is a flexible and efficient way of utilizing widely available domestic renewable resources. Syngas from biomass has the potential for biofuels production, which will enhance energy security and environmental benefits. Additionally, with the successful development of low Btu fuel engines (e.g. GE Jenbacher engines), syngas from biomass can be efficiently used for power/heat co-generation. However, biomass gasification has not been widely commercialized because of a number of technical/economic issues related to gasifier design and syngas cleanup. Biomass gasification, due to its scale limitation, cannot afford to use pure oxygen as the gasification agent that used in coal gasification.more » Because, it uses air instead of oxygen, the biomass gasification temperature is much lower than well-understood coal gasification. The low temperature leads to a lot of tar formation and the tar can gum up the downstream equipment. Thus, the biomass gasification tar removal is a critical technology challenge for all types of biomass gasifiers. This USDA/DOE funded program (award number: DE-FG36-O8GO18085) aims to develop an advanced catalytic tar conversion system that can economically and efficiently convert tar into useful light gases (such as syngas) for downstream fuel synthesis or power generation. This program has been executed by GE Global Research in Irvine, CA, in collaboration with Professor Lanny Schmidt's group at the University of Minnesota (UoMn). Biomass gasification produces a raw syngas stream containing H2, CO, CO2, H2O, CH4 and other hydrocarbons, tars, char, and ash. Tars are defined as organic compounds that are condensable at room temperature and are assumed to be largely aromatic. Downstream units in biomass gasification such as gas engine, turbine or fuel synthesis reactors require stringent control in syngas quality, especially tar content to avoid plugging (gum) of downstream equipment. Tar- and ash-free syngas streams are a critical requirement for commercial deployment of biomass-based power/heat co-generation and biofuels production. There are several commonly used syngas clean-up technologies: (1) Syngas cooling and water scrubbing has been commercially proven but efficiency is low and it is only effective at small scales. This route is accompanied with troublesome wastewater treatment. (2) The tar filtration method requires frequent filter replacement and solid residue treatment, leading to high operation and capital costs. (3) Thermal destruction typically operates at temperatures higher than 1000oC. It has slow kinetics and potential soot formation issues. The system is expensive and materials are not reliable at high temperatures. (4) In-bed cracking catalysts show rapid deactivation, with durability to be demonstrated. (5) External catalytic cracking or steam reforming has low thermal efficiency and is faced with problematic catalyst coking. Under this program, catalytic partial oxidation (CPO) is being evaluated for syngas tar clean-up in biomass gasification. The CPO reaction is exothermic, implying that no external heat is needed and the system is of high thermal efficiency. CPO is capable of processing large gas volume, indicating a very compact catalyst bed and a low reactor cost. Instead of traditional physical removal of tar, the CPO concept converts tar into useful light gases (eg. CO, H2, CH4). This eliminates waste treatment and disposal requirements. All those advantages make the CPO catalytic tar conversion system a viable solution for biomass gasification downstream gas clean-up. This program was conducted from October 1 2008 to February 28 2011 and divided into five major tasks. - Task A: Perform conceptual design and conduct preliminary system and economic analysis (Q1 2009 ~ Q2 2009) - Task B: Biomass gasification tests, product characterization, and CPO tar conversion catalyst preparation. This task will be conducted after completing process design and system economics analysis. Major milestones include identification of syngas cleaning requirements for proposed system design, identification and selection of tar compounds and 2 mixtures for use in CPO tests, and preparation of CPO catalysts for validation. (Q3 2009 ~ Q4 2009) - Task C: Test CPO with biomass gasification product gas. Optimize CPO performance with selected tar compounds. Optimize CPO performance with multi-component mixtures. Milestones include optimizing CPO catalysts design, collecting CPO experimental data for next stage kinetic modeling and understanding the effect of relative reactivities on ultimate tar conversion and syngas yields. (Q1 2010 ~ Q3 2010) - Task D: Develop tar CPO kinetic model with CPO kinetic model and modeling results as deliverables. (Q3 2010 ~ Q2 2011) - Task E: Project management and reporting. Milestone: Quarterly reports and presentations, final report, work presented at national technical conferences (Q1 2009 ~ Q2 2011) At the beginning of the program, IP landscaping was conducted to understand the operation of various types of biomass gasifiers, their unique syngas/tar compositions and potential tar mitigation options using the catalytic partial oxidation technology. A process simulation model was developed to quantify the system performance and economics impact of CPO tar removal technology. Biomass gasification product compositions used for performance evaluation tests were identified after literature review and system modeling. A reaction system for tar conversion tests was designed, constructed, with each individual component shaken-down in 2009. In parallel, University of Minnesota built a lab-scale unit and evaluated the tar removal performance using catalytic reforming. Benzene was used as the surrogate compound. The biomass gasification raw syngas composition was provided by GE through system studies. In 2010, GE selected different tar compounds and evaluated the tar removal effectiveness of the CPO catalyst. The catalytic performance was evaluated under different operating conditions, including catalyst geometry, S/C ratio, O/C ratio, GHSV, and N2 dilution. An understanding of how to optimize catalytic tar removal efficiency by varying operating conditions has been developed. GE collaborated with UoMn in examining inorganic impurities effects. Catalysts were pre-impregnated with inorganic impurities commonly present in biomass gasification syngas, including Si, Ca, Mg, Na, K, P and S. UoMn performed catalyst characterization and has acquired fundamental understandings of impurities effect on catalytic tar removal. Based on experimental data and the proposed reaction pathway, GE constructed a model to predict kinetic performance for biomass gasification tar cleanup process. Experimental data (eg. tar conversion, reactor inlet and outlet temperatures, product distribution) at different operating conditions were used to validate the model. A good fit between model predictions and experimental data was found. This model will be a valuable tool in designing the tar removal reactor and identifying appropriate operating conditions. We attended the 2011 DOE Biomass Program Thermochemical Platform Review held in Denver, CO from February 16 to 18 and received very positive comments from the review panel. Further, syngas utility and biomass to power/fuel companies expressed strong interest in our tar removal technology.« less

Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization in a recombinant transactivation assay.

PubMed

Brinkmann, Markus; Maletz, Sibylle; Krauss, Martin; Bluhm, Kerstin; Schiwy, Sabrina; Kuckelkorn, Jochen; Tiehm, Andreas; Brack, Werner; Hollert, Henner

2014-05-20

Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at contaminated sites; especially at former industrial facilities where coal tar-oil was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are frequently detected in groundwater plumes. In previous studies, fractions of groundwater with high estrogenic activity contained hetero-PAHs and their hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero-PAHs were screened for their estrogenic activity in lyticase yeast estrogen screen (LYES) and ER CALUX. All tested substances were inactive in the LYES. Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6-methylquinoline were positive in the ER CALUX, with estradiol equivalence factors (EEFs) from 2.85 × 10(-7) to 3.18 × 10(-5). The EEF values of these substances were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol A) that are sometimes found in surface water. Chemical analyses revealed that T47Dluc cells could metabolize most of the substances. Among the metabolites (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N-oxides. Because of their high concentrations measured in groundwater, we conclude that hetero-PAHs and metabolites may be a potential risk and should be the subject of further research.

Carbazole is a naturally occurring inhibitor of angiogenesis and inflammation isolated from antipsoriatic coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jack L. Arbiser; Baskaran Govindarajan; Traci E. Battle

2006-06-15

Coal tar is one of the oldest and an effective treatment for psoriasis. Coal tar has been directly applied to the skin, or used in combination with UV light as part of the Goeckerman treatment. The use of coal tar has caused long-term remissions in psoriasis, but has fallen out of favor because the treatment requires hospitalization and coal tar is poorly acceptable aesthetically to patients. Thus, determining the active antipsoriatic component of coal tar is of considerable therapeutic interest. We fractionated coal tar into its components, and tested them using the SVR angiogenesis inhibitor assay. Treatment of SVR endothelialmore » cells with coal tar fractions resulted in the isolation of a single fraction with antiangiogenic activity. The active antiangiogenic compound in coal tar is carbazole. In addition to antiangiogenic activity, carbazole inhibited the production of inflammatory IL-15 by human mononuclear cells. IL-15 is elevated in psoriasis and is thought to contribute to psoriatic inflammation. Carbazole treatment also reduced activity of inducible nitric oxide synthase (iNOS), which is proinflammatory and elevated in psoriasis. The effect of carbazole on upstream pathways in human psoriasis was determined, and carbazole was shown to inhibit signal transducer and activator of transcription (stat)3-mediated transcription, which has been shown to be relevant in human psoriasis. IL-15, iNOS, and stat3 activation require the activation of the small GTPase rac for optimal activity. Carbazole was found to inhibit rac activation as a mechanism for its inhibition of downstream inflammatory and angiogenic pathways. Given its antiangiogenic and anti-inflammatory activities, carbazole is likely a major component of the antipsoriatic activity of coal tar. Carbazole and derivatives may be useful in the therapy of human psoriasis.« less

Method and apparatus for hydrocarbon recovery from tar sands

DOEpatents

Westhoff, J.D.; Harak, A.E.

1988-05-04

A method and apparatus for utilizing tar sands having a broad range of bitumen content is disclosed. More particularly, tar sands are pyrolyzed in a cyclone retort with high temperature gases recycled from the cyclone retort to produce oil and hydrocarbon products. The spent tar sands are then burned at 2000/degree/F in a burner to remove residual char and produce a solid waste that is easily disposable. The process and apparatus have the advantages of being able to utilize tar sands having a broad range of bitumen content and the advantage of producing product gases that are free from combustion gases and thereby have a higher heating value. Another important advantage is rapid pyrolysis of the tar sands in the cyclone so as to effectively utilize smaller sized reactor vessels for reducing capitol and operating costs. 1 fig., 1 tab.

Method and apparatus for hydrocarbon recovery from tar sands

DOEpatents

Westhoff, James D.; Harak, Arnold E.

1989-01-01

A method and apparatus for utilizing tar sands having a broad range of bitumen content is disclosed. More particularly, tar sands are pyrolyzed in a cyclone retort with high temperature gases recycled from the cyclone retort to produce oil and hydrocarbon products. The spent tar sands are then burned at 2000.degree. F. in a burner to remove residual char and produce a solid waste that is easily disposable. The process and apparatus have the advantages of being able to utilize tar sands having a broad range of bitumen content and the advantage of producing product gases that are free from combustion gases and thereby have a higher heating value. Another important advantage is rapid pyrolysis of the tar sands in the cyclone so as to effectively utilize smaller sized reactor vessels for reducing capitol and operating costs.

Toxic Hazards Research Unit Annual Technical Report: 1974

DTIC Science & Technology

1974-07-01

Deuterium Fluoride 130 iv TABLE OF CONTENTS (CONT’D) Section Page Use of Ion Selective Electrodes in Inhalation Toxicology 135 Analysis of Coal Tar...Chamber Atmospheres 144 Tissue Coal Tar Analysis 145 Fractionation of Crude Coal Tar 146 Blood Cyanide (CN - ) Analysis 155 Engineering Programs 162...flask temperature 134 21 System for analysis of chamber contaminant concentration by specific ion electrode 137 22 Simplified scheme of coal tar

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

PubMed Central

van den Bogaard, Ellen H.; Bergboer, Judith G.M.; Vonk-Bergers, Mieke; van Vlijmen-Willems, Ivonne M.J.J.; Hato, Stanleyson V.; van der Valk, Pieter G.M.; Schröder, Jens Michael; Joosten, Irma; Zeeuwen, Patrick L.J.M.; Schalkwijk, Joost

2013-01-01

Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte–mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine–mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD. PMID:23348739

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis.

PubMed

van den Bogaard, Ellen H; Bergboer, Judith G M; Vonk-Bergers, Mieke; van Vlijmen-Willems, Ivonne M J J; Hato, Stanleyson V; van der Valk, Pieter G M; Schröder, Jens Michael; Joosten, Irma; Zeeuwen, Patrick L J M; Schalkwijk, Joost

2013-02-01

Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte-mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine-mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD.

Identification of transcriptional regulatory nodes in soybean defense networks using transient co-transactivation assays

PubMed Central

Wang, Yongli; Wang, Hui; Ma, Yujie; Du, Haiping; Yang, Qing; Yu, Deyue

2015-01-01

Plant responses to major environmental stressors, such as insect feeding, not only occur via the functions of defense genes but also involve a series of regulatory factors. Our previous transcriptome studies proposed that, in addition to two defense-related genes, GmVSPβ and GmN:IFR, a high proportion of transcription factors (TFs) participate in the incompatible soybean-common cutworm interaction networks. However, the regulatory mechanisms and effects of these TFs on those induced defense-related genes remain unknown. In the present work, we isolated and identified 12 genes encoding MYB, WRKY, NAC, bZIP, and DREB TFs from a common cutworm-induced cDNA library of a resistant soybean line. Sequence analysis of the promoters of three co-expressed genes, including GmVSPα, GmVSPβ, and GmN:IFR, revealed the enrichment of various TF-binding sites for defense and stress responses. To further identify the regulatory nodes composed of these TFs and defense gene promoters, we performed extensive transient co-transactivation assays to directly test the transcriptional activity of the 12 TFs binding at different levels to the three co-expressed gene promoters. The results showed that all 12 TFs were able to transactivate the GmVSPβ and GmN:IFR promoters. GmbZIP110 and GmMYB75 functioned as distinct regulators of GmVSPα/β and GmN:IFR expression, respectively, while GmWRKY39 acted as a common central regulator of GmVSPα/β and GmN:IFR expression. These corresponding TFs play crucial roles in coordinated plant defense regulation, which provides valuable information for understanding the molecular mechanisms involved in insect-induced transcriptional regulation in soybean. More importantly, the identified TFs and suitable promoters can be used to engineer insect-resistant plants in molecular breeding studies. PMID:26579162

Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain

PubMed Central

Roohk, Donald J.; Mascharak, Smita; Khambatta, Cyrus; Leung, Ho; Hellerstein, Marc

2013-01-01

The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions. Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects. The GRdim/dim mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression. To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GRdim/dim mice administered the potent GC dexamethasone (DEX). Absolute triglyceride synthesis was increased in both wild-type and GRdim/dim mice by DEX in the inguinal and epididymal fat depots. GRdim/dim mice showed an exaggerated response to DEX in both depots. De novo lipogenesis was also greatly increased in both depots in response to DEX in GRdim/dim, but not wild-type mice. In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GRdim/dim mice. Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GRdim/dim mice. Wild-type and GRdim/dim mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis. Chronic elevation of GCs in GRdim/dim mice results in severe runting and lethality. In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GRdim/dim mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully. PMID:23493372

Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30.

PubMed

Quinn, Jeffrey A; Graeber, C Thomas; Frackelton, A Raymond; Kim, Minsoo; Schwarzbauer, Jean E; Filardo, Edward J

2009-07-01

Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERalpha and ERbeta. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17beta-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin alpha5beta1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin alpha5beta1 complexes. Function-blocking antibodies directed against integrin alpha5beta1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin beta1-deficient GE11 cells, whereas reintroduction of integrin beta1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin alpha5beta1 complexes, yet this mutant did not prevent endogenous Shc-integrin alpha5beta1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin alpha5beta1.

I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp; Yoshimitsu, Makoto; Hachiman, Miho

The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner.more » Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.« less

Insights into the mechanisms of RNA secondary structure destabilization by the HIV-1 nucleocapsid protein

PubMed Central

Belfetmi, Anissa; Zargarian, Loussiné; Tisné, Carine; Sleiman, Dona; Morellet, Nelly; Lescop, Ewen; Maskri, Ouerdia; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

2016-01-01

The mature HIV-1 nucleocapsid protein NCp7 (NC) plays a key role in reverse transcription facilitating the two obligatory strand transfers. Several properties contribute to its efficient chaperon activity: preferential binding to single-stranded regions, nucleic acid aggregation, helix destabilization, and rapid dissociation from nucleic acids. However, little is known about the relationships between these different properties, which are complicated by the ability of the protein to recognize particular HIV-1 stem–loops, such as SL1, SL2, and SL3, with high affinity and without destabilizing them. These latter properties are important in the context of genome packaging, during which NC is part of the Gag precursor. We used NMR to investigate destabilization of the full-length TAR (trans activating response element) RNA by NC, which is involved in the first strand transfer step of reverse transcription. NC was used at a low protein:nucleotide (nt) ratio of 1:59 in these experiments. NMR data for the imino protons of TAR identified most of the base pairs destabilized by NC. These base pairs were adjacent to the loops in the upper part of the TAR hairpin rather than randomly distributed. Gel retardation assays showed that conversion from the initial TAR–cTAR complex to the fully annealed form occurred much more slowly at the 1:59 ratio than at the higher ratios classically used. Nevertheless, NC significantly accelerated the formation of the initial complex at a ratio of 1:59. PMID:26826129

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benowitz, N.L.; Jacob, P. III; Yu, L.

An unresolved public health issue is whether some modern cigarettes are less hazardous than other and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. The authors studied tar (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smokingmore » ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite continine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. The data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposure are considerably less than for other cigarettes.« less

Atmospheric Tar Balls: Particles from Biomass and Biofuel Burning

NASA Technical Reports Server (NTRS)

Posfai, Mihaly; Gelencser, Andras; Simonics, Renata; Arato, Krisztina; Li, Jia; Hobbs, Peter V.; Buseck, Peter R.

2004-01-01

Tar balls are amorphous, carbonaceous spherules that occur in the tropospheric aerosol as a result of biomass and biofuel burning. They form a distinct group of particles with diameters typically between 30 and 500 nm and readily identifiable with electron microscopy. Their lack of a turbostratic microstructure distinguishes them from soot, and their morphology and composition (approximately 90 mol% carbon) renders them distinct from other carbonaceous particles. Tar balls are particularly abundant in slightly aged (minutes to hours old) biomass smoke, indicating that they likely form by gas-to-particle conversion within smoke plumes. The material of tar balls is initially hygroscopic; however, the particles become largely insoluble as a result of free radical polymerization of their organic molecules. Consequently, tar balls are primarily externally mixed with other particle types, and they do not appreciably increase in size during aging. When tar balls coagulate with water-bearing particles, their material may partly dissolve and no longer be recognizable as distinct particles. Tar balls may contain organic compounds that absorb sunlight. They are an important, previously unrecognized type of carbonaceous (organic) atmospheric particle.

Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis.

PubMed

Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D

2017-11-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Macrophage Transactivation for Chemokine Production Identified as a Negative Regulator of Granulomatous Inflammation Using Agent-Based Modeling.

PubMed

Moyo, Daniel; Beattie, Lynette; Andrews, Paul S; Moore, John W J; Timmis, Jon; Sawtell, Amy; Hoehme, Stefan; Sampson, Adam T; Kaye, Paul M

2018-01-01

Cellular activation in trans by interferons, cytokines, and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and/or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling, and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani -infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation.

Skin cancer in patients with psoriasis treated with coal tar. A 25-year follow-up study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pittelkow, M.R.; Perry, H.O.; Muller, S.A.

1981-08-01

For many years, crude coal tar has been used for the treatment of psoriasis. The possible carcinogenic effect of crude coal tar and ultraviolet (UV) radiation (Goeckerman regimen), considered individually or in combination, has been of some concern to physicians. A 25-year follow-up study was completed on 280 patients with psoriasis who were hospitalized and treated with crude coal tar and UV radiation at the Mayo Clinic, Rochester, Minn, during the years 1950 through 1954. The results of this study suggest that the incidence of skin cancer is not appreciably increased above the expected incidence for the general population whenmore » patients are treated with coal tar ointments. It seems that the Goeckerman regimen (topical crude coal tar combined with UV radiation) can be used with minimal risk for skin cancer in the treatment of psoriasis.« less

Cyclin D1 Repression of Peroxisome Proliferator-Activated Receptor γ Expression and Transactivation

PubMed Central

Wang, Chenguang; Pattabiraman, Nagarajan; Zhou, Jian Nian; Fu, Maofu; Sakamaki, Toshiyuki; Albanese, Chris; Li, Zhiping; Wu, Kongming; Hulit, James; Neumeister, Peter; Novikoff, Phyllis M.; Brownlee, Michael; Scherer, Philipp E.; Jones, Joan G.; Whitney, Kathleen D.; Donehower, Lawrence A.; Harris, Emily L.; Rohan, Thomas; Johns, David C.; Pestell, Richard G.

2003-01-01

The cyclin D1 gene is overexpressed in human breast cancers and is required for oncogene-induced tumorigenesis. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor selectively activated by ligands of the thiazolidinedione class. PPARγ induces hepatic steatosis, and liganded PPARγ promotes adipocyte differentiation. Herein, cyclin D1 inhibited ligand-induced PPARγ function, transactivation, expression, and promoter activity. PPARγ transactivation induced by the ligand BRL49653 was inhibited by cyclin D1 through a pRB- and cdk-independent mechanism, requiring a region predicted to form an helix-loop-helix (HLH) structure. The cyclin D1 HLH region was also required for repression of the PPARγ ligand-binding domain linked to a heterologous DNA binding domain. Adipocyte differentiation by PPARγ-specific ligands (BRL49653, troglitazone) was enhanced in cyclin D1−/− fibroblasts and reversed by retroviral expression of cyclin D1. Homozygous deletion of the cyclin D1 gene, enhanced expression by PPARγ ligands of PPARγ and PPARγ-responsive genes, and cyclin D1−/− mice exhibit hepatic steatosis. Finally, reduction of cyclin D1 abundance in vivo using ponasterone-inducible cyclin D1 antisense transgenic mice, increased expression of PPARγ in vivo. The inhibition of PPARγ function by cyclin D1 is a new mechanism of signal transduction cross talk between PPARγ ligands and mitogenic signals that induce cyclin D1. PMID:12917338

Sampling of tar from sewage sludge gasification using solid phase adsorption.

PubMed

Ortiz González, Isabel; Pérez Pastor, Rosa Ma; Sánchez Hervás, José Ma

2012-06-01

Sewage sludge is a residue from wastewater treatment plants which is considered to be harmful to the environment and all living organisms. Gasification technology is a potential source of renewable energy that converts the sewage sludge into gases that can be used to generate energy or as raw material in chemical synthesis processes. But tar produced during gasification is one of the problems for the implementation of the gasification technology. Tar can condense on pipes and filters and may cause blockage and corrosion in the engines and turbines. Consequently, to minimize tar content in syngas, the ability to quantify tar levels in process streams is essential. The aim of this work was to develop an accurate tar sampling and analysis methodology using solid phase adsorption (SPA) in order to apply it to tar sampling from sewage sludge gasification gases. Four types of commercial SPA cartridges have been tested to determine the most suitable one for the sampling of individual tar compounds in such streams. Afterwards, the capacity, breakthrough volume and sample stability of the Supelclean™ ENVI-Carb/NH(2), which is identified as the most suitable, have been determined. Basically, no significant influences from water, H(2)S or NH(3) were detected. The cartridge was used in sampling real samples, and comparable results were obtained with the present and traditional methods.

Bacterial taxa–area and distance–decay relationships in marine environments

PubMed Central

Zinger, L; Boetius, A; Ramette, A

2014-01-01

The taxa–area relationship (TAR) and the distance–decay relationship (DDR) both describe spatial turnover of taxa and are central patterns of biodiversity. Here, we compared TAR and DDR of bacterial communities across different marine realms and ecosystems at the global scale. To obtain reliable global estimates for both relationships, we quantified the poorly assessed effects of sequencing depth, rare taxa removal and number of sampling sites. Slope coefficients of bacterial TARs were within the range of those of plants and animals, whereas slope coefficients of bacterial DDR were much lower. Slope coefficients were mostly affected by removing rare taxa and by the number of sampling sites considered in the calculations. TAR and DDR slope coefficients were overestimated at sequencing depth <4000 sequences per sample. Noticeably, bacterial TAR and DDR patterns did not correlate with each other both within and across ecosystem types, suggesting that (i) TAR cannot be directly derived from DDR and (ii) TAR and DDR may be influenced by different ecological factors. Nevertheless, we found marine bacterial TAR and DDR to be steeper in ecosystems associated with high environmental heterogeneity or spatial isolation, namely marine sediments and coastal environments compared with pelagic ecosystems. Hence, our study provides information on macroecological patterns of marine bacteria, as well as methodological and conceptual insights, at a time when biodiversity surveys increasingly make use of high-throughput sequencing technologies. PMID:24460915

HIV-1 Tat addresses dendritic cells to induce a predominant Th1-type adaptive immune response that appears prevalent in the asymptomatic stage of infection.

PubMed

Fanales-Belasio, Emanuele; Moretti, Sonia; Fiorelli, Valeria; Tripiciano, Antonella; Pavone Cossut, Maria R; Scoglio, Arianna; Collacchi, Barbara; Nappi, Filomena; Macchia, Iole; Bellino, Stefania; Francavilla, Vittorio; Caputo, Antonella; Barillari, Giovanni; Magnani, Mauro; Laguardia, Maria Elena; Cafaro, Aurelio; Titti, Fausto; Monini, Paolo; Ensoli, Fabrizio; Ensoli, Barbara

2009-03-01

Tat is an early regulatory protein that plays a major role in human HIV-1 replication and AIDS pathogenesis, and therefore, it represents a key target for the host immune response. In natural infection, however, Abs against Tat are produced only by a small fraction (approximately 20%) of asymptomatic individuals and are rarely seen in progressors, suggesting that Tat may possess properties diverting the adaptive immunity from generating humoral responses. Here we show that a Th1-type T cell response against Tat is predominant over a Th2-type B cell response in natural HIV-1 infection. This is likely due to the capability of Tat to selectively target and very efficiently enter CD1a-expressing monocyte-derived dendritic cells (MDDC), which represent a primary target for the recognition and response to virus Ag. Upon cellular uptake, Tat induces MDDC maturation and Th1-associated cytokines and beta-chemokines production and polarizes the immune response in vitro to the Th1 pattern through the transcriptional activation of TNF-alpha gene expression. This requires the full conservation of Tat transactivation activity since neither MDDC maturation nor TNF-alpha production are found with either an oxidized Tat, which does not enter MDDC, or with a Tat protein mutated in the cysteine-rich region (cys22 Tat), which enters MDDC as the wild-type Tat but is transactivation silent. Consistently with these data, inoculation of monkeys with the native wild-type Tat induced a predominant Th1 response, whereas cys22 Tat generated mostly Th2 responses, therefore providing evidence that Tat induces a predominant Th1 polarized adaptive immune response in the host.

A framework for the use of single-chemical transcriptomics data in predicting the hazards associated with complex mixtures of polycyclic aromatic hydrocarbons.

PubMed

Labib, Sarah; Williams, Andrew; Kuo, Byron; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

2017-07-01

The assumption of additivity applied in the risk assessment of environmental mixtures containing carcinogenic polycyclic aromatic hydrocarbons (PAHs) was investigated using transcriptomics. MutaTMMouse were gavaged for 28 days with three doses of eight individual PAHs, two defined mixtures of PAHs, or coal tar, an environmentally ubiquitous complex mixture of PAHs. Microarrays were used to identify differentially expressed genes (DEGs) in lung tissue collected 3 days post-exposure. Cancer-related pathways perturbed by the individual or mixtures of PAHs were identified, and dose-response modeling of the DEGs was conducted to calculate gene/pathway benchmark doses (BMDs). Individual PAH-induced pathway perturbations (the median gene expression changes for all genes in a pathway relative to controls) and pathway BMDs were applied to models of additivity [i.e., concentration addition (CA), generalized concentration addition (GCA), and independent action (IA)] to generate predicted pathway-specific dose-response curves for each PAH mixture. The predicted and observed pathway dose-response curves were compared to assess the sensitivity of different additivity models. Transcriptomics-based additivity calculation showed that IA accurately predicted the pathway perturbations induced by all mixtures of PAHs. CA did not support the additivity assumption for the defined mixtures; however, GCA improved the CA predictions. Moreover, pathway BMDs derived for coal tar were comparable to BMDs derived from previously published coal tar-induced mouse lung tumor incidence data. These results suggest that in the absence of tumor incidence data, individual chemical-induced transcriptomics changes associated with cancer can be used to investigate the assumption of additivity and to predict the carcinogenic potential of a mixture.

An extremely compensatible cigarette by design: documentary evidence on industry awareness and reactions to the Barclay filter design cheating the tar testing system.

PubMed

Kozlowski, L T; Dreschel, N A; Stellman, S D; Wilkenfeld, J; Weiss, E B; Goldberg, M E

2005-02-01

The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol. To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981. Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined. Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off. The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs.

False promises: the tobacco industry, "low tar" cigarettes, and older smokers.

PubMed

Cataldo, Janine K; Malone, Ruth E

2008-09-01

To investigate the role of the tobacco industry in marketing to and sustaining tobacco addiction among older smokers and aging baby boomers, We performed archival searches of electronic archives of internal tobacco company documents using a snowball sampling approach. Analysis was done using iterative and comparative review of documents, classification by themes, and a hermeneutic interpretive approach to develop a case study. Based on extensive marketing research, tobacco companies aggressively targeted older smokers and sought to prevent them from quitting. Innovative marketing approaches were used. "Low tar" cigarettes were developed in response to the health concerns of older smokers, despite industry knowledge that such products had no health advantage and did not help smokers quit. Tobacco industry activities influence the context of cessation for older smokers in several ways. Through marketing "low tar" or "light" cigarettes to older smokers "at risk" of quitting, the industry contributes to the illusion that such cigarettes are safer, although "light" cigarettes may make it harder for addicted smokers to quit. Through targeted mailings of coupons and incentives, the industry discourages older smokers from quitting. Through rhetoric aimed at convincing addicted smokers that they alone are responsible for their smoking, the industry contributes to self-blame, a documented barrier to cessation. Educating practitioners, older smokers, and families about the tobacco industry's influence may decrease the tendency to "blame the victim," thereby enhancing the likelihood of older adults receiving tobacco addiction treatment. Comprehensive tobacco control measures must include a focus on older smokers.

Zac1, an Sp1-like protein, regulates human p21{sup WAF1/Cip1} gene expression in HeLa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Pei-Yao; Hsieh, Tsai-Yuan; Liu, Shu-Ting

2011-12-10

Zac1 functions as both a transcription factor and a transcriptional cofactor for p53, nuclear receptors (NRs) and NR coactivators. Zac1 might also act as a transcriptional repressor via the recruitment of histone deacetylase 1 (HDAC1). The ability of Zac1 to interact directly with GC-specific elements indicates that Zac1 possibly binds to Sp1-responsive elements. In the present study, our data show that Zac1 is able to interact directly with the Sp1-responsive element in the p21{sup WAF1/Cip1} gene promoter and enhance the transactivation activity of Sp1 through direct physical interaction. Our data further demonstrate that Zac1 might enhance Sp1-specific promoter activity bymore » interacting with the Sp1-responsive element, affecting the transactivation activity of Sp1 via a protein-protein interaction, or competing the HDAC1 protein away from the pre-existing Sp1/HDAC1 complex. Finally, the synergistic regulation of p21{sup WAF1/Cip1} gene expression by Zac1 and Sp1 is mediated by endogenous p53 protein and p53-responsive elements in HeLa cells. Our work suggests that Zac1 might serve as an Sp1-like protein that directly interacts with the Sp1-responsive element to oligomerize with and/or to coactivate Sp1.« less

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.

PubMed

Forrester, Steven J; Kawai, Tatsuo; O'Brien, Shannon; Thomas, Walter; Harris, Raymond C; Eguchi, Satoru

2016-01-01

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

Upregulating endogenous genes by an RNA-programmable artificial transactivator

PubMed Central

Fimiani, Cristina; Goina, Elisa; Mallamaci, Antonello

2015-01-01

To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action. PMID:26152305

Potential contributions of asphalt and coal tar to black carbon quantification in urban dust, soils, and sediments

USGS Publications Warehouse

Yang, Y.; Mahler, B.J.; Van Metre, P.C.; Ligouis, B.; Werth, C.J.

2010-01-01

Measurements of black carbon (BC) using either chemical or thermal oxidation methods are generally thought to indicate the amount of char and/or soot present in a sample. In urban environments, however, asphalt and coal-tar particles worn from pavement are ubiquitous and, because of their pyrogenic origin, could contribute to measurements of BC. Here we explored the effect of the presence of asphalt and coal-tar particles on the quantification of BC in a range of urban environmental sample types, and evaluated biases in the different methods used for quantifying BC. Samples evaluated were pavement dust, residential and commercial area soils, lake sediments from a small urban watershed, and reference materials of asphalt and coal tar. Total BC was quantified using chemical treatment through acid dichromate (Cr2O7) oxidation and chemo-thermal oxidation at 375??C (CTO-375). BC species, including soot and char/charcoal, asphalt, and coal tar, were quantified with organic petrographic analysis. Comparison of results by the two oxidation methods and organic petrography indicates that both coal tar and asphalt contribute to BC quantified by Cr2O7 oxidation, and that coal tar contributes to BC quantified by CTO-375. These results are supported by treatment of asphalt and coal-tar reference samples with Cr2O7 oxidation and CTO-375. The reference asphalt is resistant to Cr2O7 oxidation but not to CTO-375, and the reference coal tar is resistant to both Cr2O7 oxidation and CTO-375. These results indicate that coal tar and/or asphalt can contribute to BC measurements in samples from urban areas using Cr2O7 oxidation or CTO-375, and caution is advised when interpreting BC measurements made with these methods. ?? 2010 Elsevier Ltd.

Polycyclic aromatic hydrocarbon (PAHs) and hopanes in stranded tar-balls on the coasts of Peninsular Malaysia: applications of biomarkers for identifying sources of oil pollution.

PubMed

Zakaria, M P; Okuda, T; Takada, H

2001-12-01

Malaysian coasts are subjected to various threats of petroleum pollution including routine and accidental oil spill from tankers, spillage of crude oils from inland and off-shore oil fields, and run-off from land-based human activities. Due to its strategic location, the Straits of Malacca serves as a major shipping lane. This paper expands the utility of biomarker compounds, hopanes, in identifying the source of tar-balls stranded on Malaysian coasts. 20 tar-ball samples collected from the east and west coast were analyzed for hopanes and polycyclic aromatic hydrocarbons (PAHs). Four of the 13 tar-ball samples collected from the west coast of Peninsular Malaysia were identified as the Middle East crude oil (MECO) based on their biomarker signatures, suggesting tanker-derived sources significantly contributing the petroleum pollution in the Straits of Malacca. The tar-balls found on the east coast seem to originate from the offshore oil platforms in the South China Sea. The presence of South East Asian crude oil (SEACO) tar-balls on the west coast carry several plausible explanations. Some of the tar-balls could have been transported via sea currents from the east coast. The tankers carrying SEACO to other countries could have accidentally spilt the oil as well. Furthermore, discharge of tank washings and ballast water from the tankers were suggested based on the abundance in higher molecular weight n-alkanes and the absence of unresolved complex mixture (UCM) in the tar-ball samples. The other possibilities are that the tar-balls may have been originated from the Sumatran oil fields and spillage of domestic oil from oil refineries in Port Dickson and Malacca. The results of PAHs analysis suggest that all the tar-ball samples have undergone various extent of weathering through evaporation, dissolution and photooxidation.

Characterization of alkanes, hopanes, and polycyclic aromatic hydrocarbons (PAHs) in tar-balls collected from the East Coast of Peninsular Malaysia.

PubMed

Chandru, Kuhan; Zakaria, Mohamad Pauzi; Anita, Sofia; Shahbazi, Azadeh; Sakari, Mahyar; Bahry, Pourya Shahpoury; Mohamed, Che Abd Rahim

2008-05-01

The East Coast of Peninsular Malaysia faces the South China Sea and is vulnerable to oil pollution because of intense petroleum production activities in the area. The South China Sea is also a favored route for supertankers carrying crude oil to the Far East. Consequently, oil spills can occur, causing pollution and contamination in the surrounding areas. Residual oil spills stranded on coastal beaches usually end up as tar-balls. Elucidating the sources of tar-balls using a molecular marker approach is essential in assessing environmental impacts and perhaps settling legal liabilities for affected parties. This study utilizes a multimodal molecular marker approach through the use of diagnostic ratios of alkanes, hopanes, and polycyclic aromatic hydrocarbons (PAHs) to determine the source, distribution and weathering of tar-balls. Hopane ratios (e.g., C29/C30, and summation C31-C35/C30 ratios) were used to identify the sources of tar-balls. The weathering effects were distinguished by using alkanes, namely the unresolved complex mixture (UCM) and low molecular weight/high molecular weight (L/H) ratios. Similarly, PAHs were also used for the determination of weathering processes undergone by the tar-balls. This multimodal molecular marker gave a very strong indication of the sources of tar-balls in this study. For example, 16 out of 17 samples originated from South East Asian Crude Oil (SEACO) with one sample from Merang, Terengganu originating from North Sea Oil (Troll). The TRME-2 sample may have come from a supertanker's ballast water discharge. The second possibility is that the tar-ball may have been transported via oceanographic currents. All 'weathered' sample characterizations were based on the presence of UCM and other ratios. The multimodal molecular marker approach applied in this study has enabled us to partially understand the transport behavior of tar-balls in the marine environment and has revealed insights into the weathering process of tar-balls.

Transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α by perfluoroalkyl carboxylates and sulfonates: estimation of PFOA induction equivalency factors.

PubMed

Ishibashi, Hiroshi; Kim, Eun-Young; Iwata, Hisato

2011-04-01

The present study assessed the transactivation potencies of the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α (BS PPARα) by perfluorochemicals (PFCs) having various carbon chain lengths (C4-C12) using an in vitro reporter gene assay. Among the twelve PFCs treated with a range of 7.8-250 μM concentration, eight perfluoroalkyl carboxylates (PFCAs) and two perfluoroalkyl sulfonates (PFSAs) induced BS PPARα-mediated transcriptional activities in a dose-dependent manner. To compare the BS PPARα transactivation potencies of PFCs, the present study estimated the PFOA induction equivalency factors (IEFs), a ratio of the 50% effective concentration of PFOA to the concentration of each compound that can induce the response corresponding to 50% of the maximal response of PFOA. The order of IEFs for the PFCs was as follows: PFOA (IEF: 1)>PFHpA (0.89)>PFNA (0.61)>PFPeA (0.50)>PFHxS (0.41)>PFHxA (0.38)≈PFDA (0.37)>PFBA (0.26)=PFOS (0.26)>PFUnDA (0.15)≫PFDoDA and PFBuS (not activated). The structure-activity relationship analysis showed that PFCAs having more than seven perfluorinated carbons had a negative correlation (r=-1.0, p=0.017) between the number of perfluorinated carbons and the IEF of PFCAs, indicating that the number of perfluorinated carbon of PFCAs is one of the factors determining the transactivation potencies of the BS PPARα. The analysis also indicated that PFCAs were more potent than PFSAs with the same number of perfluorinated carbons. Treatment with a mixture of ten PFCs showed an additive action on the BS PPARα activation. Using IEFs of individual PFCs and hepatic concentrations of PFCs in the liver of wild Baikal seals, the PFOA induction equivalents (IEQs, 5.3-58 ng IEQ/g wet weight) were calculated. The correlation analysis revealed that the hepatic total IEQs showed a significant positive correlation with the hepatic expression levels of cytochrome P450 4A-like protein (r=0.53, p=0.036). This suggests that our approach may be useful for assessing the potential PPARα-mediated biological effects of complex mixtures of PFCs in wild Baikal seal population.

Porous Carbon Nanofibers from Electrospun Biomass Tar/Polyacrylonitrile/Silver Hybrids as Antimicrobial Materials.

PubMed

Song, Kunlin; Wu, Qinglin; Zhang, Zhen; Ren, Suxia; Lei, Tingzhou; Negulescu, Ioan I; Zhang, Quanguo

2015-07-15

A novel route to fabricate low-cost porous carbon nanofibers (CNFs) using biomass tar, polyacrylonitrile (PAN), and silver nanoparticles has been demonstrated through electrospinning and subsequent stabilization and carbonization processes. The continuous electrospun nanofibers had average diameters ranging from 392 to 903 nm. The addition of biomass tar resulted in increased fiber diameters, reduced thermal stabilities, and slowed cyclization reactions of PAN in the as-spun nanofibers. After stabilization and carbonization, the resultant CNFs showed more uniformly sized and reduced average diameters (226-507 nm) compared to as-spun nanofibers. The CNFs exhibited high specific surface area (>400 m(2)/g) and microporosity, attributed to the combined effects of phase separations of the tar and PAN and thermal decompositions of tar components. These pore characteristics increased the exposures and contacts of silver nanoparticles to the bacteria including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, leading to excellent antimicrobial performances of as-spun nanofibers and CNFs. A new strategy is thus provided for utilizing biomass tar as a low-cost precursor to prepare functional CNFs and reduce environmental pollutions associated with direct disposal of tar as an industrial waste.

Theoretical studies of structure and selectivity of 5-methyl-4-(2-thiazolylazo) resorcinol as a sensor for metal ions: DFT calculation

NASA Astrophysics Data System (ADS)

Thaomola, Sukhontip; Sompech, Supachai

2018-05-01

The global minimum optimized structures of the free sensor 5-methyl-4-(2-thiazolylazo) resorcinol (5-Me-TAR) and 5-Me-TAR-Cu2+ complexes in the gas phase have been investigated by using Density Functional Theory (DFT) with the def2-TZVP basis set. To compare the selectivity of 5-Me-TAR for metal ions, the binding energy of 5-Me-TAR with various metal ions (Na+, K+, Mg2+, Ca2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Pd2+, Cd2+ and Hg2+) were calculated at the same level as the theory. Binding energy values of most transition metal ions are lower than alkaline earth metal ions and alkali metal ions, respectively. The 5-Me-TAR sensor shows the highest selectivity with the Cu2+ ion. Moreover, Dependent Density Functional Theory (TDDFT) results confirm that the 5-Me-TAR-Cu2+ complex is stabilized by the sensor to metal charge transfer process. The computational studies suggested that the 5-Me-TAR is suitable for Cu2+ ion detection sensor development.

Deciphering structure-activity relationships in a series of Tat/TAR inhibitors.

PubMed

Pascale, Lise; González, Alejandro López; Di Giorgio, Audrey; Gaysinski, Marc; Teixido Closa, Jordi; Tejedor, Roger Estrada; Azoulay, Stéphane; Patino, Nadia

2016-11-01

A series of pentameric "Polyamide Amino Acids" (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs. This led us to suggest two distinct interaction modes that have been further validated by molecular modeling studies. While the binding of Tat competitor PAAs induces a contraction at the TAR bulge region, the binding of non-competitor ones widens it. This could account for the distinct PAA ability to compete with Tat fragment. Our work illustrates how comparative thermodynamic studies of a series of RNA ligands of same chemical family are of value for understanding their binding modes and for rationalizing structure-activity relationships.

Coal-tar-based pavement sealcoat—Potential concerns for human health and aquatic life

USGS Publications Warehouse

Mahler, Barbara J.; Woodside, Michael D.; Van Metre, Peter C.

2016-04-20

Aquatic Life Concerns—Runoff from coal-tar-sealcoated pavement, even runoff collected more than 3 months after sealcoat application, is acutely toxic to fathead minnows and water fleas, two species commonly used to assess toxicity to aquatic life. Exposure to even highly diluted runoff from coal-tar-sealcoated pavement can cause DNA damage and impair DNA repair. These findings demonstrate that coal-tar-sealcoat runoff can remain a risk to aquatic life for months after application.

Relation Between PAHs and Coal-Tar-Based Pavement Sealant in Urban Environments (Invited)

NASA Astrophysics Data System (ADS)

Mahler, B. J.; van Metre, P. C.

2010-12-01

Since 2003, coal-tar-based sealant products have come under increased scrutiny as a source of PAHs in urban environments. Sealant (or sealcoat) is the black, shiny substance often applied to asphalt pavement, in particular parking lots and driveways, for esthetic and maintenance purposes. Coal-tar-based sealant, one of the two primary pavement sealant types on the market, typically is 20-35 percent coal-tar pitch, a known carcinogen that is more than 50 percent polycyclic aromatic hydrocarbons (PAHs). The PAH content of the coal-tar-based sealant product is about 1,000 times that of a similar, asphalt-based product, on average. This difference is reflected in regional differences in sealant use and PAH concentrations in pavement dust. In the central and eastern U.S., where the coal-tar-based formulation is prevalent, ΣPAH in mobile particles from sealed pavement have been shown to be about 1,000 times higher than in the western U.S., where the asphalt-based formulation is prevalent (the median ΣPAH concentrations are 2,200 mg/kg in the central and eastern U.S. and 2.1 mg/kg in the western U.S.). Source apportionment modeling indicates that, in the central and eastern U.S., particles from sealed pavement are contributing the majority of the PAHs in recently deposited (post-1990) lake sediment, with implications for ecological health, and that coal-tar-based sealant is the primary cause of upward trends in PAHs in U.S. urban lakes. From the standpoint of human health, research indicates that mobile particles from parking lots with coal-tar-based sealant are tracked indoors, resulting in elevated PAH concentrations in house dust. Coal-tar-based sealcoat being applied to an asphalt parking lot at the University of Texas Pickle Research Center.

Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

PubMed

Suk, Hyung; Knipe, David M

2015-06-01

The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selected constituents in the smokes of U. S. commercial cigaretts: tar, nicotine, carbon monoxide and carbon dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.A.; Quincy, R.B.; Guerin, M.R.

One hundred twenty-one brands of United States commercial cigarettes were analyzed for their deliveries of tar, nicotine, carbon monoxide, and carbon dioxide under standard analytical smoking conditions. The sample included both filter and nonfilter cigarettes. Comparisons of carbon monoxide deliveries over the range of observed tar deliveries indicated a very high correlation between CO and tar for filter cigarettes, but nonfilter cigarettes tended to produce much less CO than would have been predicted from their tar deliveries. Comparison of ORNL nicotine values for specific brands with those determined by the Federal Trade Commission yield no statistically significant differences between laboratories.more » 4 figures, 6 tables.« less

Development of secondary chamber for tar cracking-improvement of wood pyrolysis performance in pre-vacuum chamber

NASA Astrophysics Data System (ADS)

Siahaan, S.; Homma, H.; Homma, H.

2018-02-01

Energy crisis and global warming, in other words, climate change are critical topics discussed in various parts of the world. Global warming primarily result from too much emission of carbon dioxide (CO2) in the atmosphere. To mitigate global warming, or climate change and improve electrification in rural areas, wood pyrolysis technology is developed in a laboratory scale, of which gases are directly applicable to the gas engine generator. Our laboratory has developed a prototype of wood pyrolysis plant with a pre-vacuum chamber. However, tar yield was around 40 wt% of feedstock. This research aims to reduce tar yield by secondary tar cracking. For the secondary tar cracking, a secondary pre-vacuum chamber is installed after primary pre-vacuum chamber. Gases generated in the primary pre-vacuum chamber are lead into the secondary chamber that is heated up to 1000 K. This paper reports performance of the secondary chamber for secondary tar cracking in homogeneous mode and heterogeneous mode with char.

Thermocatalytic treatment of biomass tar model compounds via radio frequency.

PubMed

Anis, Samsudin; Zainal, Z A; Bakar, M Z A

2013-05-01

A new effective RF tar thermocatalytic treatment process with low energy intensive has been proposed to remove tar from biomass gasification. Toluene and naphthalene as biomass tar model compounds were removed via both thermal and catalytic treatment over a wide temperature range from 850 °C to 1200 °C and 450 °C to 900 °C, respectively at residence time of 0-0.7 s. Thermal characteristics of the new technique are also described in this paper. This study clearly clarified that toluene was much easier to be removed than naphthalene. Soot was found as the final product of thermal treatment of the tar model and completely removed during catalytic treatment. Radical reactions generated by RF non-thermal effect improve the tar removal. The study showed that Y-zeolite has better catalytic activity compared to dolomite on toluene and naphthalene removal due to its acidic nature and large surface area, even at lower reaction temperature of about 550 °C. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microwave-induced cracking of pyrolytic tars coupled to microwave pyrolysis for syngas production.

PubMed

Beneroso, D; Bermúdez, J M; Montes-Morán, M A; Arenillas, A; Menéndez, J A

2016-10-01

Herein a new process is proposed to produce a syngas-rich gas fraction (>80vol% H2+CO) from biowaste based on microwave heating within two differentiated steps in order to avoid tars production. The first step consists of the microwave pyrolysis of biowaste induced by a char-based susceptor at 400-800°C; tars, char and syngas-rich gas fractions being produced. The tars are then fed into the second step where a portion of the char from the first step is used as a bed material in a 0.3:1wt% ratio. This bed is heated up by microwaves up to 800°C, allowing thermal cracking of tars and additional syngas (>90vol% H2+CO) being then produced. This new concept arises as an alternative technology to the gasification of biowastes for producing syngas with no need for catalysts or gasifying reagents to minimise tars production. Copyright © 2016 Elsevier Ltd. All rights reserved.

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

PubMed Central

Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

2017-01-01

Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes. PMID:27998979

Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1.

PubMed

Ohkura, Naganari; Nagamura, Yuko; Tsukada, Toshihiko

2008-10-15

In extraskeletal myxoid chondrosarcoma, a chromosomal translocation creates a gene fusion between EWS and an orphan nuclear receptor, NOR1. The resulting fusion protein EWS/NOR1 has been believed to lead to malignant transformation by functioning as a transactivator for NOR1-target genes. By comparing the gene expression profiles of NOR1- and EWS/NOR1-overexpressing cells, we found that they largely shared up-regulated genes, but no significant correlation was observed with respect to the transactivation levels of each gene. In addition, the proteins associated with NOR1 and EWS/NOR1 were mostly the same in these cells. The results suggest that these proteins differentially transactivate overlapping target genes through a similar transcriptional machinery. To clarify the mechanisms underlying the transcriptional divergence between NOR1 and EWS/NOR1, we searched for alternatively associated proteins, and identified poly(ADP-ribose) polymerase I (PARP-1) as an NOR1-specific binding protein. Consistent with its binding properties, PARP-1 acted as a transcriptional repressor of NOR1, but not EWS/NOR1, in a luciferase reporter assay employing PARP-1(-/-) fibroblasts. Interestingly, suppressive activity of PARP-1 was observed in a DNA response element-specific manner, and in a subtype-specific manner toward the NR4A family (Nur77, Nurr1, and NOR1), suggesting that PARP-1 plays a role in the diversity of transcriptional regulation mediated by the NR4A family in normal cells. Altogether, our findings suggest that NOR1 and EWS/NOR1 regulate overlapping target genes differently by utilizing associated proteins, including PARP-1; and that EWS/NOR1 may acquire oncogenic activities by avoiding (or gaining) transcription factor-specific modulation by the associated proteins. (c) 2008 Wiley-Liss, Inc.

Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells.

PubMed

Kannappan, Ramaswamy; Mattapally, Saidulu; Wagle, Pooja A; Zhang, Jianyi

2018-05-18

The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells. Exposure to low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) measured by RAD50 and MRE11 expression, Checkpoint kinase 2 activation and γH2A.X recruitment at DNA strand breaks in both the cell groups indicating silencing p53-TAD do not affect DDR mechanism upstream of p53. Following removal of Doxo p53-WT hiPS cells underwent DNA repair, corrected their damaged DNA and restored DNA integrity. Conversely, p53-TAD KO hiPS cells did not undergo complete DNA repair and failed to restore DNA integrity. More importantly continuous culture of p53-TAD KO hiPS cells underwent G2/M cell cycle arrest and expressed cellular senescent marker p16 INK4a . Our data clearly shows that silencing transactivation domain of p53 did not affect DDR but affected the DNA repair process implying the crucial role of p53 transactivation domain in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent senescence.

Pyrolysis of aseptic packages (tetrapak) in a laboratory screw type reactor and secondary thermal/catalytic tar decomposition.

PubMed

Haydary, J; Susa, D; Dudáš, J

2013-05-01

Pyrolysis of aseptic packages (tetrapak cartons) in a laboratory apparatus using a flow screw type reactor and a secondary catalytic reactor for tar cracking was studied. The pyrolysis experiments were realized at temperatures ranging from 650 °C to 850 °C aimed at maximizing of the amount of the gas product and reducing its tar content. Distribution of tetrapak into the product yields at different conditions was obtained. The presence of H2, CO, CH4, CO2 and light hydrocarbons, HCx, in the gas product was observed. The Aluminum foil was easily separated from the solid product. The rest part of char was characterized by proximate and elemental analysis and calorimetric measurements. The total organic carbon in the tar product was estimated by elemental analysis of tars. Two types of catalysts (dolomite and red clay marked AFRC) were used for catalytic thermal tar decomposition. Three series of experiments (without catalyst in a secondary cracking reactor, with dolomite and with AFRC) at temperatures of 650, 700, 750, 800 and 850 °C were carried out. Both types of catalysts have significantly affected the content of tars and other components in pyrolytic gases. The effect of catalyst on the tetrapack distribution into the product yield on the composition of gas and on the total organic carbon in the tar product is presented in this work. Copyright © 2013 Elsevier Ltd. All rights reserved.

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed Central

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-01-01

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. Images PMID:1408831

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-10-11

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

Cutaneous Papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling

PubMed Central

Brimer, Nicole; Lyons, Charles; Wallberg, Annika E.; Vande Pol, Scott B.

2011-01-01

Papillomavirus E6 oncoproteins associate with LXXLL motifs on target cellular proteins to alter their function. Using a proteomic approach, we found the E6 oncoproteins of cutaneous papillomaviruses Bovine Papillomavirus Type 1 (BE6) and HPV types 1 and 8 (1E6 and 8E6) associated with the MAML1 transcriptional co-activator. All three E6 proteins bind to an acidic LXXLL motif at the carboxy-terminus of MAML1 and repress transactivation by MAML1. MAML1 is best known as the co-activator and effector of NOTCH induced transcription, and BPV-1 E6 represses synthetic NOTCH responsive promoters, endogenous NOTCH responsive promoters, and is found in a complex with MAML1 in stably transformed cells. BPV-1 induced papillomas show characteristics of repressed NOTCH signal transduction, including suprabasal expression of integrins, talin, and basal type keratins, and delayed expression of the NOTCH dependent HES1 transcription factor. These observations give rise to a model whereby papillomavirus oncoproteins including BPV-1 E6 and the cancer associated HPV-8 E6 repress Notch induced transcription, thereby delaying keratinocyte differentiation. PMID:22249263

29 CFR 1915.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 7 2014-07-01 2014-07-01 false Coal tar pitch volatiles; interpretation of term. 1915.1002 Section 1915.1002 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Toxic and Hazardous Substances § 1915.1002 Coal tar pitch volatiles; interpretation of term. Note: The...

29 CFR 1915.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false Coal tar pitch volatiles; interpretation of term. 1915.1002 Section 1915.1002 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Toxic and Hazardous Substances § 1915.1002 Coal tar pitch volatiles; interpretation of term. Note: The...

29 CFR 1926.1102 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 8 2014-07-01 2014-07-01 false Coal tar pitch volatiles; interpretation of term. 1926.1102 Section 1926.1102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Hazardous Substances § 1926.1102 Coal tar pitch volatiles; interpretation of term. Note: The requirements...

29 CFR 1926.1102 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false Coal tar pitch volatiles; interpretation of term. 1926.1102 Section 1926.1102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Hazardous Substances § 1926.1102 Coal tar pitch volatiles; interpretation of term. Note: The requirements...

29 CFR 1926.1102 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 8 2012-07-01 2012-07-01 false Coal tar pitch volatiles; interpretation of term. 1926.1102 Section 1926.1102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Hazardous Substances § 1926.1102 Coal tar pitch volatiles; interpretation of term. Note: The requirements...

29 CFR 1926.1102 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Coal tar pitch volatiles; interpretation of term. 1926.1102 Section 1926.1102 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Hazardous Substances § 1926.1102 Coal tar pitch volatiles; interpretation of term. Note: The requirements...

29 CFR 1915.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 7 2013-07-01 2013-07-01 false Coal tar pitch volatiles; interpretation of term. 1915.1002 Section 1915.1002 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Toxic and Hazardous Substances § 1915.1002 Coal tar pitch volatiles; interpretation of term. Note: The...

29 CFR 1915.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 7 2012-07-01 2012-07-01 false Coal tar pitch volatiles; interpretation of term. 1915.1002 Section 1915.1002 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Toxic and Hazardous Substances § 1915.1002 Coal tar pitch volatiles; interpretation of term. Note: The...

29 CFR 1915.1002 - Coal tar pitch volatiles; interpretation of term.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Coal tar pitch volatiles; interpretation of term. 1915.1002 Section 1915.1002 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH... Toxic and Hazardous Substances § 1915.1002 Coal tar pitch volatiles; interpretation of term. Note: The...

Selected constituents in the smoke of domestic low tar cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griest, W. H.; Quincy, R. B.; Guerin, M. R.

Thirty-two brands of domestic commercial low tar and nicotine cigarettes were analyzed for their production of tar, nicotine, nitrogen oxides (as nitric oxide), hydrogen cyanide, acrolein, carbon monoxide and carbon dioxide under standard analytical smoking conditions. Results are compared with published data for certain brands.

48 CFR Appendix to Part 1252 - Tar Matrix

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Tar Matrix Appendix to Part 1252 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Pt. 1252, App. Appendix to Part 1252—Tar Matrix ER27DE05.000...

The potential use of tar sand bitumen as paving asphalt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, J.C.

1988-01-01

In this paper several research reports describing the preparation of potential paving asphalts from tar sand bitumen are reviewed and the results of the studies compared. The tar sand asphalts described in the studies were prepared from 1) hot water-recovered bitumen from deposits near San Luis Obispo, California (Edna deposits), and deposits near Vernal and Sunnyside, Utah; and 2) bitumen recovered from the Northwest Asphalt Ridge deposits near Vernal, Utah, by both in situ steamflood and in situ combustion recovery processes. Important properties of the tar sand asphalts compare favorably with those of specification petroleum asphalts. Laboratory data suggest thatmore » some tar sand asphalts may have superior aging characteristics and produce more water-resistant paving mixtures than typical petroleum asphalts.« less

Influence of cigarette filter ventilation on smokers' mouth level exposure to tar and nicotine.

PubMed

Caraway, John W; Ashley, Madeleine; Bowman, Sheri A; Chen, Peter; Errington, Graham; Prasad, Krishna; Nelson, Paul R; Shepperd, Christopher J; Fearon, Ian M

2017-12-01

Cigarette filter ventilation allows air to be drawn into the filter, diluting the cigarette smoke. Although machine smoking reveals that toxicant yields are reduced, it does not predict human yields. The objective of this study was to investigate the relationship between cigarette filter ventilation and mouth level exposure (MLE) to tar and nicotine in cigarette smokers. We collated and reviewed data from 11 studies across 9 countries, in studies performed between 2005 and 2013 which contained data on MLE from 156 products with filter ventilation between 0% and 87%. MLE among 7534 participants to tar and nicotine was estimated using the part-filter analysis method from spent filter tips. For each of the countries, MLE to tar and nicotine tended to decrease as filter ventilation increased. Across countries, per-cigarette MLE to tar and nicotine decreased as filter ventilation increased from 0% to 87%. Daily MLE to tar and nicotine also decreased across the range of increasing filter ventilation. These data suggest that on average smokers of highly ventilated cigarettes are exposed to lower amounts of nicotine and tar per cigarette and per day than smokers of cigarettes with lower levels of ventilation. Copyright © 2017 British American Tobacco. Published by Elsevier Inc. All rights reserved.

Marketing 'less harmful, low-tar' cigarettes is a key strategy of the industry to counter tobacco control in China.

PubMed

Yang, Gonghuan

2014-03-01

While the 'low-tar' scheme has been widely recognised as a misleading tactic used by the tobacco industry to deceive the public about the true risks of cigarette smoking, a similar campaign using the slogan of 'less harmful, low tar' was launched by the Chinese tobacco industry, that is, State Tobacco Monopoly Administration/China National Tobacco Corporation and began to gain traction during the last decade. Despite the fact that no sufficient research evidence supports the claims made by the industry that these cigarettes are safer, the Chinese tobacco industry has continued to promote them using various health claims. As a result, the production and sales of 'less harmful, low-tar' cigarettes have increased dramatically since 2000. Recently, a tobacco industry senior researcher, whose main research area is 'less harmful, low-tar' cigarettes, was elected as an Academician to the prestigious Chinese Academy of Engineering for his contribution to developing 'less harmful, low-tar' cigarettes. The tobacco researcher's election caused an outcry from the tobacco control community and the general public in China. This paper discusses the Chinese tobacco industry's 'less harmful, low-tar' initiatives and calls for the Chinese government to stop the execution of this deceptive strategy for tobacco marketing.

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

PubMed

Manukjan, Georgi; Bösing, Hendrik; Schmugge, Markus; Strauß, Gabriele; Schulze, Harald

2017-11-01

Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome. © 2017 John Wiley & Sons Ltd.

Human Body Size in Military Aircraft and Personal Equipment

DTIC Science & Technology

1946-06-01

manufacturers and others for use in the manufacti or purchase of supplies, or for any other purpose, the Goernment assumes responsibility nor obligation... responsibility ’ of the designer and the manufacturer to h’ave provided:tolerancesin the plane in’ order to insure efficient installation of the equipment...ional dependability. At the out-break of Y;orld Tar II, the Army Air Forces had no responsibility .n the development and procurement of flying clothing

Atmospheric tar balls from biomass burning in Mexico

NASA Astrophysics Data System (ADS)

Adachi, K.; Buseck, P. R.

2009-12-01

Tar balls are spherical, organic aerosol particles that result from biofuel or biomass burning. They absorb sunlight and cause warming of the atmosphere. Although distinctive when viewed with a transmission electron microscope (TEM) because of their spherical shape, much remains to be determined about details of their compositions, occurrences, and generation. Here we aim to characterize the occurrences of tar balls using individual-particle analyses with a TEM and to study their formation in young biomass-burning smoke. The samples were collected using the U.S. Forest Service Twin Otter aircraft during the MILAGRO (Megacity Initiative: Local and Global Research Observations) campaign conducted in March 2006. We analyzed 84 TEM grid samples from ~30 biomass-burning events near Mexico City and over Yucatan. Sixty samples were from young smoke (less than an hour old), and others were from haze that mainly occurred from biomass burning. Tar balls have neither an evident nucleus nor are they normally attached to other particles. They are almost perfectly spherical on TEM grids, indicating that they were solid when collected. It appears as if tar balls consist of lower volatility organic matter than many other organic aerosol particles. On average, 9% by number of biomass-burning aerosol particles were tar balls in samples collected between a few minutes to an hour after emission. On the other hand, samples collected within a few minutes after emission included few or no tar balls. The occurrences and abundances of atmospheric tar balls are important when evaluating the effects of smoke on local and regional climate.

Ground-water contamination by organic bases derived from coal-tar wastes

USGS Publications Warehouse

Pereira, Wilfred E.; Rostad, Colleen E.; Garbarino, John R.; Hult, Marc F.

1983-01-01

A fluid sample from a shallow aquifer contaminated by coal-tar wastes was analyzed for organic bases. The sample consisted of a mixture of aqueous and oily-tar phases. The phases were separated by centrifugation and filtration. Organic bases were isolated from each phase by pH adjustment and solvent extraction. Organic bases in the oily-tar phase were further purified by neutral-alumina, micro-column adsorption chromatography. Separation and identification of the organic bases in each phase were achieved by using capillary gas chromatography-mass spectrometry-computer (GC-MS-COM) and probe distillation-high resolution mass spectrometry (PD-HRMS) techniques. Organic bases present in the aqueous phase included primary aromatic amines (such as aniline, alkylated anilines, and naphthylamines) as well as azaarenes (such as alkylated pyridines, quinolines, acridine, and benzoquinolines). The oily-tar phase contained acridine, benzacridines, dibenzacridines, and numerous other azaarenes, the elemental compositions of which were determined by PD-HRMS. Azaarenes in the oily-tar phase, varying in size from 6 to 12 rings, are reported for the first time. The origin and environmental significance of these compounds are discussed.

Groundwater contamination by organic bases derived from coal-tar wastes

USGS Publications Warehouse

Pereira, W.E.; Rostad, C.E.; Garbarino, J.R.; Hult, M.F.

1983-01-01

A fluid sample from a shallow aquifer contaminated by coal-tar wastes was analyzed for organic bases. The sample consisted of a mixture of aqueous and oily-tar phases. The phases were separated by centrifugation and filtration. Organic bases were isolated from each phase by pH adjustment and solvent extraction. Organic bases in the oily-tar phase were further purified by neutral-alumina, micro-column adsorption chromatography. Separation and identification of the organic bases in each phase were achieved by using capillary gas chromatography-mass spectrometry-computer (GC-MS-COM) and probe distillation-high resolution mass spectrometry (PD-HRMS) techniques. Organic bases present in the aqueous phase included primary aromatic amines (such as aniline, alkylated anilines, and naphthylamines) as well as azaarenes (such as alkylated pyridines, quinolines, acridine, and benzoquinolines). The oily-tar phase contained acridine, benzacridines, dibenzacridines, and numerous other azaarenes, the elemental compositions of which were determined by PD-HRMS. Azaarenes in the oily-tar phase, varying in size from 6 to 12 rings, are reported for the first time. The origin and environmental significance of these compounds are discussed. ?? 1983.

Partitioning studies of coal-tar constituents in a two-phase contaminated ground-water system

USGS Publications Warehouse

Rostad, C.E.; Pereira, W.E.; Hult, M.F.

1985-01-01

Organic compounds derived from coal-tar wastes in a contaminated aquifer in St. Louis Park, Minnesota, were identified, and their partition coefficients between the tar phase and aqueous phase were determined and compared with the corresponding n-octanol/water partition coefficients. Coal tar contains numerous polycyclic aromatic compounds, many of which are suspected carcinogens or mutagens. Groundwater contamination by these toxic compounds may pose an environmental health hazard in nearby public water-supply wells. Fluid samples from this aquifer developed two phases upon settling: an upper aqueous phase, and a lower oily-tar phase. After separating the phases, polycyclic aromatic compounds in each phase were isolated using complexation with N-methyl-2-pyrrolidone and identified by fused-silica capillary gas chromatography/mass spectrometry. Thirty-one of the polycyclic aromatic compounds were chosen for further study from four different classes: 12 polycyclic aromatic hydrocarbons, 10 nitrogen heterocycles, 5 sulfur heterocycles, and 4 oxygen heterocycles. Within each compound class, the tar/water partition coefficients of these compounds were reasonably comparable with the respective n-octanol/water partition coefficient.

Fractal-like Tar Ball Aggregates from Wildfire Smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Girotto, Giulia; China, Swarup; Bhandari, Janarjan

Tar balls are atmospheric particles abundant in slightly aged biomass burning smoke and have a significant, but highly uncertain, role on Earth's radiative balance. Tar balls are typically detected using electron microscopy; they are resistant to the electron beam, and generally, they are observed as individual spheres. Here, we report new observations of a significant fraction of tar ball aggregates (~27% by number) from samples collected in a plume of the Whitewater-Baldy Complex fire in New Mexico. The structure of these aggregates is fractal-like and follows a scale invariant power law similar to that of soot particles, despite the considerablymore » larger size and smaller number of monomers. We also present observations of tar ball aggregates from four other geographical locations, including from a remote high elevation site in the North Atlantic Ocean. Aggregation affects the particle optical properties and therefore, their climatic impact. We performed numerical simulations based on the observed morphology and estimated the effects of aggregation on the tar balls optical properties. We find that aggregation can enhance single scattering albedo by up to 41%.« less

Assessment of tar pollution on the United Arab emirates beaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abu-Hilal, A.H.; Khordagui, H.K.

1993-01-01

In light of the inadequate information concerning stranded tar on the southwest beaches of the Arabian Gulf and the Gulf of Oman, particularly following the massive oil releases during the Gulf War, the present investigation was designed to provide reference-integrated information on the nature, location, and levels of stranded tar balls on the beaches of the United Arab Emirates (UAE). The recorded levels appeared to be higher than expected or previously reported. The tar distribution pattern, in addition to the degree of weathering, indicates that the massive oil release during the Gulf War did not reach the UAE shorelines. Themore » highest reported levels of stranded tar ever recorded in the Arabian Gulf at Jabal Dhannah apparently originated from oil spills and tankers' ballast water at the main oil terminal at the Al-Ruwaiss oil refinery some 10 km to the east. The surprising, relatively high levels of stranded tar on the beaches of the Gulf of Oman were solely attributed to the heavy navigation traffic close to the shorelines. 19 refs., 2 figs., 3 tabs.« less

A randomized, investigator-masked clinical evaluation of the efficacy and safety of clobetasol propionate 0.05% shampoo and tar blend 1% shampoo in the treatment of moderate to severe scalp psoriasis.

PubMed

Griffiths, Christopher E M; Finlay, Andrew Y; Fleming, Colin J; Barker, Jonathan N W N; Mizzi, Fabienne; Arsonnaud, Stéphanie

2006-01-01

The clinical benefit of currently available tar blend shampoos for the treatment of scalp psoriasis is restricted due to their limited efficacy, low cosmetic appeal and potential for carcinogenicity. This 4-week multicentre, randomized, parallel-group, investigator-masked study included 162 subjects and aimed to compare the efficacy, safety and cosmetic acceptability of clobetasol propionate 0.05% shampoo versus a currently marketed tar blend 1% shampoo in subjects with moderate to severe scalp psoriasis. Clobetasol propionate shampoo was superior to tar blend shampoo with respect to all efficacy variables tested (p<0.001): Total and Global Severity Score; erythema; plaque thickening; desquamation; pruritus; total scalp area involved; and the subject's global assessment of clinical improvement. Both treatments were safe and well-tolerated. Furthermore, more subjects indicated that clobetasol propionate shampoo was more cosmetically acceptable than tar blend shampoo. Clobetasol propionate 0.05% shampoo is a good alternative to tar blend shampoo in the treatment of moderate to severe scalp psoriasis.

Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.

PubMed

Jeong, Soo-Jin; Lu, Hanxin; Cho, Won-Kyung; Park, Hyeon Ung; Pise-Masison, Cynthia; Brady, John N

2006-10-01

In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2.

PubMed

Stuart, Jennifer H; Sumner, Rebecca P; Lu, Yongxu; Snowden, Joseph S; Smith, Geoffrey L

2016-12-01

The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells. Ectopic expression of C6 inhibits the induction of interferon stimulated genes (ISGs) in response to IFNα treatment at both the mRNA and protein level. C6 inhibits the IFNα-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway at a late stage, downstream of STAT1 and STAT2 phosphorylation, nuclear translocation and binding of the interferon stimulated gene factor 3 (ISGF3) complex to the interferon stimulated response element (ISRE). Mechanistically, C6 associates with the transactivation domain of STAT2 and this might explain how C6 inhibits the type I IFN signalling very late in the pathway. During virus infection C6 reduces ISRE-dependent gene expression despite the presence of the viral protein phosphatase VH1 that dephosphorylates STAT1 and STAT2. The ability of a cytoplasmic replicating virus to dampen the immune response within the nucleus, and the ability of viral immunomodulators such as C6 to inhibit multiple stages of the innate immune response by distinct mechanisms, emphasizes the intricacies of host-pathogen interactions and viral immune evasion.

Structure-based design of ligands for protein basic domains: Application to the HIV-1 Tat protein

NASA Astrophysics Data System (ADS)

Filikov, Anton V.; James, Thomas L.

1998-05-01

A methodology has been developed for designing ligands to bind a flexible basic protein domain where the structure of the domain is essentially known. It is based on an empirical binding free energy function developed for highly charged complexes and on Monte Carlo simulations in internal coordinates with both the ligand and the receptor being flexible. HIV-1 encodes a transactivating regulatory protein called Tat. Binding of the basic domain of Tat to TAR RNA is required for efficient transcription of the viral genome. The structure of a biologically active peptide containing the Tat basic RNA-binding domain is available from NMR studies. The goal of the current project is to design a ligand which will bind to that basic domain and potentially inhibit the TAR-Tat interaction. The basic domain contains six arginine and two lysine residues. Our strategy was to design a ligand for arginine first and then a superligand for the basic domain by joining arginine ligands with a linker. Several possible arginine ligands were obtained by searching the Available Chemicals Directory with DOCK 3.5 software. Phytic acid, which can potentially bind multiple arginines, was chosen as a building block for the superligand. Calorimetric binding studies of several compounds to methylguanidine and Arg-/Lys-containing peptides were performed. The data were used to develop an empirical binding free energy function for prediction of affinity of the ligands for the Tat basic domain. Modeling of the conformations of the complexes with both the superligand and the basic domain being flexible has been carried out via Biased Probability Monte Carlo (BPMC) simulations in internal coordinates (ICM 2.6 suite of programs). The simulations used parameters to ensure correct folding, i.e., consistent with the experimental NMR structure of a 25-residue Tat peptide, from a random starting conformation. Superligands for the basic domain were designed by joining together two molecules of phytic acid with peptidic and peptidomimetic linkers. The linkers were refined by varying the length and side chains of the linking residues, carrying out BPMC simulations, and evaluation of the binding free energy for the best energy conformation. The dissociation constant of the best ligand designed is estimated to be in the low- to mid-nanomolar range.

Characterization of a novel transcriptionally active domain in the transforming growth factor beta-regulated Smad3 protein.

PubMed

Prokova, Vassiliki; Mavridou, Sofia; Papakosta, Paraskevi; Kardassis, Dimitris

2005-01-01

Transforming growth factor beta (TGFbeta) regulates transcriptional responses via activation of cytoplasmic effector proteins termed Smads. Following their phosphorylation by the type I TGFbeta receptor, Smads form oligomers and translocate to the nucleus where they activate the transcription of TGFbeta target genes in cooperation with nuclear cofactors and coactivators. In the present study, we have undertaken a deletion analysis of human Smad3 protein in order to characterize domains that are essential for transcriptional activation in mammalian cells. With this analysis, we showed that Smad3 contains two domains with transcriptional activation function: the MH2 domain and a second middle domain that includes the linker region and the first two beta strands of the MH2 domain. Using a protein-protein interaction assay based on biotinylation in vivo, we were able to show that a Smad3 protein bearing an internal deletion in the middle transactivation domain is characterized by normal oligomerization and receptor activation properties. However, this mutant has reduced transactivation capacity on synthetic or natural promoters and is unable to interact physically and functionally with the histone acetyltransferase p/CAF. The loss of interaction with p/CAF or other coactivators could account, at least in part, for the reduced transactivation capacity of this Smad3 mutant. Our data support an essential role of the previously uncharacterized middle region of Smad3 for nuclear functions, such as transcriptional activation and interaction with coactivators.

Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach.

PubMed

de la Fuente, Cynthia; Gupta, Madhur V; Klase, Zachary; Strouss, Katharine; Cahan, Patrick; McCaffery, Timothy; Galante, Anthony; Soteropoulos, Patricia; Pumfery, Anne; Fujii, Masahiro; Kashanchi, Fatah

2006-07-05

Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-kappaB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.

Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300.

PubMed

Mori, N; Morishita, M; Tsukazaki, T; Giam, C Z; Kumatori, A; Tanaka, Y; Yamamoto, N

2001-04-01

Human T-cell leukemia virus type I (HTLV-I) Tax is a potent transcriptional regulator that can activate or repress specific cellular genes and that has been proposed to contribute to leukemogenesis in adult T-cell leukemia. Previously, HTLV-I- infected T-cell clones were found to be resistant to growth inhibition by transforming growth factor (TGF)-beta. Here it is shown that Tax can perturb Smad-dependent TGF-beta signaling even though no direct interaction of Tax and Smad proteins could be detected. Importantly, a mutant Tax of CREB-binding protein (CBP)/p300 binding site, could not repress the Smad transactivation function, suggesting that the CBP/p300 binding domain of Tax is essential for the suppression of Smad function. Because both Tax and Smad are known to interact with CBP/p300 for the potentiation of their transcriptional activities, the effect of CBP/p300 on suppression of Smad-mediated transactivation by Tax was examined. Overexpression of CBP/p300 reversed Tax-mediated inhibition of Smad transactivation. Furthermore, Smad could repress Tax transcriptional activation, indicating reciprocal repression between Tax and Smad. These results suggest that Tax interferes with the recruitment of CBP/p300 into transcription initiation complexes on TGF-beta-responsive elements through its binding to CBP/p300. The novel function of Tax as a repressor of TGF-beta signaling may contribute to HTLV-I leukemogenesis. (Blood. 2001;97:2137-2144)

Non-Natural Linker Configuration in 2,6-Dipeptidyl-Anthraquinones Enhances the Inhibition of TAR RNA Binding/Annealing Activities by HIV-1 NC and Tat Proteins.

PubMed

Sosic, Alice; Saccone, Irene; Carraro, Caterina; Kenderdine, Thomas; Gamba, Elia; Caliendo, Giuseppe; Corvino, Angela; Di Vaio, Paola; Fiorino, Ferdinando; Magli, Elisa; Perissutti, Elisa; Santagada, Vincenzo; Severino, Beatrice; Spada, Valentina; Fabris, Dan; Frecentese, Francesco; Gatto, Barbara

2018-06-12

The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of anti-retrovirals by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle. Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidyl-anthraquinones as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to the basic side chains. We show here that the non-natural linker configuration imparted unexpected TAR RNA targeting properties to the 2,6-peptidyl-anthraquinones and significantly enhanced their potency. Even if the new compounds were able to interact directly with the NC protein, they manifested a consistently higher affinity for the TAR RNA substrate and their TAR-binding properties mirrored their ability to interfere with NC-TAR interactions. Based on these findings, we propose that the viral Tat protein, sharing the same RNA substrate but acting in distinct phases of the viral life cycle, constitutes an additional druggable target for this class of peptidyl-anthraquinones. The inhibition of Tat-TAR interaction for the test compounds correlated again with their TAR-binding properties, while simultaneously failing to demonstrate any direct Tat-binding capabilities. These considerations highlighted the importance of TAR RNA in the elucidation of their inhibition mechanism, rather than direct protein inhibition. We have therefore identified anti-TAR compounds with dual in vitro inhibitory activity on different viral proteins, demonstrating that it is possible to develop multitarget compounds capable of interfering with processes mediated by the interactions of this essential RNA domain of HIV-1 genome with NC and Tat proteins.

An extremely compensatible cigarette by design: documentary evidence on industry awareness and reactions to the Barclay filter design cheating the tar testing system

PubMed Central

Kozlowski, L; Dreschel, N; Stellman, S; Wilkenfeld, J; Weiss, E; Goldberg, M

2005-01-01

Background: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol. Objectives: To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981. Methods: Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined. Results: Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off. Conclusion: The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs. PMID:15735303

Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells.

PubMed

Cui, Jiajia; Qin, Lingfeng; Zhang, Junwei; Abrahimi, Parwiz; Li, Hong; Li, Guangxin; Tietjen, Gregory T; Tellides, George; Pober, Jordan S; Mark Saltzman, W

2017-08-04

Human endothelial cells are initiators and targets of the rejection response. Pre-operative modification of endothelial cells by small interfering RNA transfection could shape the nature of the host response post-transplantation. Ablation of endothelial cell class II major histocompatibility complex molecules by small interfering RNA targeting of class II transactivator can reduce the capacity of human endothelial cells to recruit and activate alloreactive T cells. Here, we report the development of small interfering RNA-releasing poly(amine-co-ester) nanoparticles, distinguished by their high content of a hydrophobic lactone. We show that a single transfection of small interfering RNA targeting class II transactivator attenuates major histocompatibility complex class II expression on endothelial cells for at least 4 to 6 weeks after transplantation into immunodeficient mouse hosts. Furthermore, silencing of major histocompatibility complex class II reduces allogeneic T-cell responses in vitro and in vivo. These data suggest that poly(amine-co-ester) nanoparticles, potentially administered during ex vivo normothermic machine perfusion of human organs, could be used to modify endothelial cells with a sustained effect after transplantation.The use of gene silencing techniques in the treatment of post-transplantation host rejection is not long lasting and can have systemic effects. Here, the authors utilize a nanocarrier for siRNA for treatment of arteries ex vivo prior to implantation subsequently attenuating immune reaction in vivo.

The Transactivation Domain of Marek's Disease Virus (MDV) Meq Oncoprotein Does Not Affect Tumor Incidence But Plays a Role in Tumor Phenotype

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus encoded oncoprotein, Meq, is responsible for the tumorigenic phenotype of the virus. We have previously shown that replacement of the meq gene in the very virulent strain Md5 with that of vaccine strain CVI988/Rispens results in virus attenuation in chickens. To determine the...

Estimating tar and nicotine exposure: human smoking versus machine generated smoke yields.

PubMed

St Charles, F K; Kabbani, A A; Borgerding, M F

2010-02-01

Determine human smoked (HS) cigarette yields of tar and nicotine for smokers using their own brand in their everyday environment. A robust, filter analysis method was used to estimate the tar and nicotine yields for 784 subjects. Seventeen brands were chosen to represent a wide range of styles: 85 and 100 mm lengths; menthol and non-menthol; 17, 23, and 25 mm circumference; with tar yields [Federal Trade Commission (FTC) method] ranging from 1 to 18 mg. Tar bands chosen corresponded to yields of 1-3 mg, 4-6 mg, 7-12 mg, and 13+ mg. A significant difference (p<0.0001) in HS yields of tar and nicotine between tar bands was found. Machine-smoked yields were reasonable predictors of the HS yields for groups of subjects, but the relationship was neither exact nor linear. Neither the FTC, the Massachusetts (MA) nor the Canadian Intensive (CI) machine-smoking methods accurately reflect the HS yields across all brands. The FTC method was closest for the 7-12 mg and 13+ mg products and the MA method was closest for the 1-3mg products. The HS yields for the 4-6 mg products were approximately midway between the FTC and the MA yields. HS nicotine yields corresponded well with published urinary and plasma nicotine biomarker studies. 2009 Elsevier Inc. All rights reserved.

Relationship between cigarette format and mouth-level exposure to tar and nicotine in smokers of Russian king-size cigarettes.

PubMed

Ashley, Madeleine; Dixon, Mike; Prasad, Krishna

2014-10-01

Differences in length and circumference of cigarettes may influence smoker behaviour and exposure to smoke constituents. Superslim king-size (KSSS) cigarettes (17mm circumference versus 25mm circumference of conventional king-size [KS] cigarettes), have gained popularity in several countries, including Russia. Some smoke constituents are lower in machine-smoked KSSS versus KS cigarettes, but few data exist on actual exposure in smokers. We investigated mouth-level exposure (MLE) to tar and nicotine in Russian smokers of KSSS versus KS cigarettes and measured smoke constituents under machine-smoking conditions. MLE to tar was similar for smokers of 1mg ISO tar yield products, but lower for smokers of 4mg and 7mg KSSS versus KS cigarettes. MLE to nicotine was lower in smokers of 4mg KSSS versus KS cigarettes, but not for other tar bands. No gender differences were observed for nicotine or tar MLE. Under International Organization for Standardization, Health Canada Intense and Massachusetts regimes, KSSS cigarettes tended to yield less carbon monoxide, acetaldehyde, nitric oxide, acrylonitrile, benzene, 1,3-butadiene and tobacco-specific nitrosamines, but more formaldehyde, than KS cigarettes. In summary, differences in MLE were observed between cigarette formats, but not systematically across pack tar bands. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sydney Tar Ponds Remediation: Experience to China

ERIC Educational Resources Information Center

Liu, Fan; Bryson, Ken A.

2009-01-01

The infamous "Sydney Tar Ponds" are well known as one of the largest toxic waste sites of Canada, due to almost 100 years of steelmaking in Sydney, a once beautiful and peaceful city located on the east side of Cape Breton Island, Nova Scotia. This article begins with a contextual overview of the Tar Ponds issue including a brief…

77 FR 5833 - Notice of Availability of the Draft Programmatic Environmental Impact Statement for Allocation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... of the Draft Programmatic Environmental Impact Statement for Allocation of Oil Shale and Tar Sands... of Oil Shale and Tar Sands Resources on Lands Administered by the BLM in Colorado, Utah, and Wyoming... preferred method of commenting. Mail: Addressed to: Oil Shale and Tar Sands Resources Draft Programmatic EIS...

33 CFR 165.927 - Safety Zone; St. Louis River, Duluth/Interlake Tar Remediation Site, Duluth, MN.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone; St. Louis River, Duluth/Interlake Tar Remediation Site, Duluth, MN. 165.927 Section 165.927 Navigation and Navigable... Coast Guard District § 165.927 Safety Zone; St. Louis River, Duluth/Interlake Tar Remediation Site...

In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital warts.

PubMed Central

Cowsert, L M; Fox, M C; Zon, G; Mirabelli, C K

1993-01-01

Papillomaviruses induce benign proliferative lesions, such as genital warts, in humans. The E2 gene product is thought to play a major role in the regulation of viral transcription and DNA replication and may represent a rational target for an antisense oligonucleotide drug action. Phosphorothioate oligonucleotides complementary to E2 mRNAs were synthesized and tested in a series of in vitro bovine papillomavirus (BPV) and human papillomavirus (HPV) models for the ability to inhibit E2 transactivation and virus-induced focus formation. The most active BPV-specific compounds were complementary to the mRNA cap region (ISIS 1751), the translation initiation region for the full-length E2 transactivator (ISIS 1753), and the translation initiation region for the E2 transrepressor mRNA (ISIS 1755). ISIS 1751 and ISIS 1753 were found to reduce E2-dependent transactivation and viral focus formation in a sequence-specific and concentration-dependent manner. ISIS 1755 increased E2 transactivation in a dose-dependent manner but had no effect on focus formation. Oligonucleotides with a chain length of 20 residues had optimal activity in the E2 transactivation assay. On the basis of the above observations, ISIS 2105, a 20-residue phosphorothioate oligonucleotide targeted to the translation initiation of both HPV type 6 (HPV-6) and HPV-11 E2 mRNA, was designed and shown to inhibit E2-dependent transactivation by HPV-11 E2 expressed from a surrogate promoter. These observations support the rationale of E2 as a target for antiviral therapy against papillomavirus infections and specifically identify ISIS 2105 as a candidate antisense oligonucleotide for the treatment of genital warts induced by HPV-6 and HPV-11. Images PMID:8383937

Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation

PubMed Central

Reinchisi, Gisela; Parada, Margarita; Lois, Pablo; Oyanadel, Claudia; Shaughnessy, Ronan; Gonzalez, Alfonso; Palma, Verónica

2013-01-01

Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell (NSC) proliferation. How these signals cooperate is therefore critical for understanding normal brain development and function. Here we report a novel acute effect of Shh signaling on EGFR function. We show that during late neocortex development, Shh mediates the activation of the ERK1/2 signaling pathway in Radial Glial cells (RGC) through EGFR transactivation. This process is dependent on metalloprotease activity and accounts for almost 50% of the EGFR-dependent mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known model for studying the EGFR receptor function, Shh also induces cell proliferation involving EGFR activation, as reflected by EGFR internalization and ERK1/2 phosphorylation. These findings may have important implications for understanding the mechanisms that regulate NSC proliferation during neurogenesis and may lead to novel approaches to the treatment of tumors. PMID:24133411

Which Came First?

NASA Image and Video Library

2015-09-16

The workings of the Martian winds are visible in this image of sand dunes trapped inside an unnamed crater in southern Terra Cimmeria captured by NASA Mars Reconnaissance Orbiter spacecraft. Many of the craters in the Southern highlands of Mars contain sand dunes, and HiRISE is still in the process of mapping these dunes and determining how active they are today. So far, the dunes in these craters appear to be a mixed bunch, with some dunes actively advancing while others seem to be frozen in place. This image will be compared to a previous picture, to see how these dunes have changed since 2008. The sand dunes are the large, branched ridges and dark patches that are conspicuous against the bright background, particularly in the northwest corner of our picture. There are also signs of two other wind-related processes: smaller, brighter ridges line the floor of the crater in regularly spaced rows. These are also windblown deposits, mysterious "transverse aeolian ridges" or TARs that are more common in the Martian tropics. Faint, irregular dark lines cross the dunes and the TARs, marking the tracks of dust devils that vacuum the surface during southern summer. So, which came first? We can untangle the history of these processes by looking at the picture more closely. Over most of the image, it is obvious that the dark sand dunes bury the bright TARs, meaning that the sand dunes are younger than the TARs. But this relationship is not so clear for the southernmost dune we see in this picture. Here, the TARs look like they extend into the dune and merge with ripples on the dune's surface, suggesting that the TARs might be younger than the dunes. The question can be resolved by carefully examining an enhanced color cutout. The TARs are brighter and redder than the sand dunes and this color persists on the crests of the TARs as the sand encroaches, burying the valleys first and then the slopes and finally the TAR crests. This tells us that the unusual appearance of the dune margin is caused by burial and exposure of the older TARs by the younger sand. Finally, you can trace the tracks of dust devils crossing over the dunes, telling us that they are younger than the dunes. So, first came the TARs, next the dunes, and last the dust devils -- probably within the last few months! http://photojournal.jpl.nasa.gov/catalog/?IDNumber=pia19941

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haydary, J., E-mail: juma.haydary@stuba.sk; Susa, D.; Dudáš, J.

Highlights: ► Pyrolysis of aseptic packages was carried out in a laboratory flow reactor. ► Distribution of tetrapak into the product yields was obtained. ► Composition of the pyrolysis products was estimated. ► Secondary thermal and catalytic decomposition of tars was studied. ► Two types of catalysts (dolomite and red clay marked AFRC) were used. - Abstract: Pyrolysis of aseptic packages (tetrapak cartons) in a laboratory apparatus using a flow screw type reactor and a secondary catalytic reactor for tar cracking was studied. The pyrolysis experiments were realized at temperatures ranging from 650 °C to 850 °C aimed at maximizingmore » of the amount of the gas product and reducing its tar content. Distribution of tetrapak into the product yields at different conditions was obtained. The presence of H{sub 2}, CO, CH{sub 4}, CO{sub 2} and light hydrocarbons, HCx, in the gas product was observed. The Aluminum foil was easily separated from the solid product. The rest part of char was characterized by proximate and elemental analysis and calorimetric measurements. The total organic carbon in the tar product was estimated by elemental analysis of tars. Two types of catalysts (dolomite and red clay marked AFRC) were used for catalytic thermal tar decomposition. Three series of experiments (without catalyst in a secondary cracking reactor, with dolomite and with AFRC) at temperatures of 650, 700, 750, 800 and 850 °C were carried out. Both types of catalysts have significantly affected the content of tars and other components in pyrolytic gases. The effect of catalyst on the tetrapack distribution into the product yield on the composition of gas and on the total organic carbon in the tar product is presented in this work.« less

The impact of steam and current density on carbon formation from biomass gasification tar on Ni/YSZ, and Ni/CGO solid oxide fuel cell anodes

NASA Astrophysics Data System (ADS)

Mermelstein, Joshua; Millan, Marcos; Brandon, Nigel

The combination of solid oxide fuel cells (SOFCs) and biomass gasification has the potential to become an attractive technology for the production of clean renewable energy. However the impact of tars, formed during biomass gasification, on the performance and durability of SOFC anodes has not been well established experimentally. This paper reports an experimental study on the mitigation of carbon formation arising from the exposure of the commonly used Ni/YSZ (yttria stabilized zirconia) and Ni/CGO (gadolinium-doped ceria) SOFC anodes to biomass gasification tars. Carbon formation and cell degradation was reduced through means of steam reforming of the tar over the nickel anode, and partial oxidation of benzene model tar via the transport of oxygen ions to the anode while operating the fuel cell under load. Thermodynamic calculations suggest that a threshold current density of 365 mA cm -2 was required to suppress carbon formation in dry conditions, which was consistent with the results of experiments conducted in this study. The importance of both anode microstructure and composition towards carbon deposition was seen in the comparison of Ni/YSZ and Ni/CGO anodes exposed to the biomass gasification tar. Under steam concentrations greater than the thermodynamic threshold for carbon deposition, Ni/YSZ anodes still exhibited cell degradation, as shown by increased polarization resistances, and carbon formation was seen using SEM imaging. Ni/CGO anodes were found to be more resilient to carbon formation than Ni/YSZ anodes, and displayed increased performance after each subsequent exposure to tar, likely due to continued reforming of condensed tar on the anode.

A comparison of physicochemical methods for the remediation of porous medium systems contaminated with tar

NASA Astrophysics Data System (ADS)

Hauswirth, Scott C.; Miller, Cass T.

2014-10-01

The remediation of former manufactured gas plant (FMGP) sites contaminated with tar DNAPLs (dense non-aqueous phase liquids) presents a significant challenge. The tars are viscous mixtures of thousands of individual compounds, including known and suspected carcinogens. This work investigates the use of combinations of mobilization, solubilization, and chemical oxidation approaches to remove and degrade tars and tar components in porous medium systems. Column experiments were conducted using several flushing solutions, including an alkaline-polymer (AP) solution containing NaOH and xanthan gum (XG), a surfactant-polymer (SP) solution containing Triton X-100 surfactant (TX100) and XG, an alkaline-surfactant-polymer (ASP) solution containing NaOH, TX100, and XG, and base-activated sodium persulfate both with and without added TX100. The effectiveness of the flushing solutions was assessed based on both removal of polycyclic aromatic hydrocarbon (PAH) mass and on the reduction of dissolved-phase PAH concentrations. SP flushes of 6.6 to 20.9 PV removed over 99% of residual PAH mass and reduced dissolved-phase concentrations by up to two orders of magnitude. ASP flushing efficiently removed 95-96% of residual PAH mass within about 2 PV, and significantly reduced dissolved-phase concentrations of several low molar mass compounds, including naphthalene, acenaphthene, fluorene, and phenanthrene. AP flushing removed a large portion of the residual tar (77%), but was considerably less effective than SP and ASP in terms of the effect on dissolved PAH concentrations. Persulfate was shown to oxidize tar components, primarily those with low molar mass, however, the overall degradation was relatively low (30-50% in columns with low initial tar saturations), and the impact on dissolved-phase concentrations was minimal.

Upgrading producer gas quality from rubber wood gasification in a radio frequency tar thermocatalytic treatment reactor.

PubMed

Anis, Samsudin; Zainal, Z A

2013-12-01

This study focused on improving the producer gas quality using radio frequency (RF) tar thermocatalytic treatment reactor. The producer gas containing tar, particles and water was directly passed at a particular flow rate into the RF reactor at various temperatures for catalytic and thermal treatments. Thermal treatment generates higher heating value of 5.76 MJ Nm(-3) at 1200°C. Catalytic treatments using both dolomite and Y-zeolite provide high tar and particles conversion efficiencies of about 97% on average. The result also showed that light poly-aromatic hydrocarbons especially naphthalene and aromatic compounds particularly benzene and toluene were still found even at higher reaction temperatures. Low energy intensive RF tar thermocatalytic treatment was found to be effective for upgrading the producer gas quality to meet the end user requirements and increasing its energy content. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dimerization of BTas is required for the transactivational activity of bovine foamy virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan Juan; Qiao Wentao; Xu Fengwen

2008-06-20

The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46-62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activitymore » on the LTR and IP. Furthermore, BTas ({delta}46-62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV.« less

I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions.

PubMed

Kusano, Shuichi; Yoshimitsu, Makoto; Hachiman, Miho; Ikeda, Masanori

2015-12-01

The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. Copyright © 2015 Elsevier Inc. All rights reserved.

Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.

PubMed

He, Zhiheng; Liu, Yunhua; Liang, Deguang; Wang, Zhuo; Robertson, Erle S; Lan, Ke

2010-02-01

Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.

Two distinct cellular proteins interact with the EIa-responsive element of an adenovirus early promoter.

PubMed Central

Jansen-Durr, P; Wintzerith, M; Reimund, B; Hauss, C; Kédinger, C

1990-01-01

EIa-dependent transactivation of the adenovirus EIIa early (EIIaE) promoter is correlated with the activation of the cellular transcription factor E2F. In this study we identified a cellular protein, C alpha, that is distinct from E2F and that binds two sites in the EIIaE promoter, one of which overlaps with the proximal E2F binding site of the EIIaE promoter. The possible involvement of C alpha in the EIa responsiveness of this promoter is discussed. Images PMID:2139142

Coal-Tar-Based Parking Lot Sealcoat: An Unrecognized Source of PAH to Settled House Dust

PubMed Central

2010-01-01

Despite much speculation, the principal factors controlling concentrations of polycyclic aromatic hydrocarbons (PAH) in settled house dust (SHD) have not yet been identified. In response to recent reports that dust from pavement with coal-tar-based sealcoat contains extremely high concentrations of PAH, we measured PAH in SHD from 23 apartments and in dust from their associated parking lots, one-half of which had coal-tar-based sealcoat (CT). The median concentration of total PAH (T-PAH) in dust from CT parking lots (4760 μg/g, n = 11) was 530 times higher than that from parking lots with other pavement surface types (asphalt-based sealcoat, unsealed asphalt, concrete [median 9.0 μg/g, n = 12]). T-PAH in SHD from apartments with CT parking lots (median 129 μg/g) was 25 times higher than that in SHD from apartments with parking lots with other pavement surface types (median 5.1 μg/g). Presence or absence of CT on a parking lot explained 48% of the variance in log-transformed T-PAH in SHD. Urban land-use intensity near the residence also had a significant but weaker relation to T-PAH. No other variables tested, including carpeting, frequency of vacuuming, and indoor burning, were significant. PMID:20063893

The extraction of bitumen from western oil sands. Final report, July 1989--September 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oblad, A.G.; Bunger, J.W.; Dahlstrom, D.A.

1994-03-01

Research and development of surface extraction and upgrading processes of western tar sands are described. Research areas included modified hot water, fluidized bed, and rotary kiln pyrolysis of tar sands for extraction of bitumen. Bitumen upgrading included solvent extraction of bitumen, and catalytic hydrotreating of bitumen. Characterization of Utah tar sand deposits is also included.

76 FR 21003 - Notice of Intent To Prepare a Programmatic Environmental Impact Statement (EIS) and Possible Land...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... Allocation of Oil Shale and Tar Sands Resources on Lands Administered by the Bureau of Land Management in... to prepare a Programmatic EIS for Allocation of Oil Shale and Tar Sands Resources on Lands... following methods: Web site: http://blm.gov/st5c . Mail: BLM Oil Shale and Tar Sands Resources Leasing...

Thermodynamic analysis of tar reforming through auto-thermal reforming process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nurhadi, N., E-mail: nurhadi@tekmira.esdm.go.id; Diniyati, Dahlia; Efendi, M. Ade Andriansyah

2015-12-29

Fixed bed gasification is a simple and suitable technology for small scale power generation. One of the disadvantages of this technology is producing tar. So far, tar is not utilized yet and being waste that should be treated into a more useful product. This paper presents a thermodynamic analysis of tar conversion into gas producer through non-catalytic auto-thermal reforming technology. Tar was converted into components, C, H, O, N and S, and then reacted with oxidant such as mixture of air or pure oxygen. Thus, this reaction occurred auto-thermally and reached chemical equilibrium. The sensitivity analysis resulted that the mostmore » promising process performance occurred at flow rate of air was reached 43% of stoichiometry while temperature of process is 1100°C, the addition of pure oxygen is 40% and preheating of oxidant flow is 250°C. The yield of the most promising process performance between 11.15-11.17 kmol/h and cold gas efficiency was between 73.8-73.9%.The results of this study indicated that thermodynamically the conversion of tar into producer gas through non-catalytic auto-thermal reformingis more promising.« less

Brown carbon absorption in the red and near-infrared spectral region

NASA Astrophysics Data System (ADS)

Hoffer, András; Tóth, Ádám; Pósfai, Mihály; Eddy Chung, Chul; Gelencsér, András

2017-06-01

Black carbon (BC) aerosols have often been assumed to be the only light-absorbing carbonaceous particles in the red and near-infrared spectral regions of solar radiation in the atmosphere. Here we report that tar balls (a specific type of organic aerosol particles from biomass burning) do absorb red and near-infrared radiation significantly. Tar balls were produced in a laboratory experiment, and their chemical and optical properties were measured. The absorption of these particles in the range between 470 and 950 nm was measured with an aethalometer, which is widely used to measure atmospheric aerosol absorption. We find that the absorption coefficient of tar balls at 880 nm is more than 10 % of that at 470 nm. The considerable absorption of red and infrared light by tar balls also follows from their relatively low absorption Ångström coefficient (and significant mass absorption coefficient) in the spectral range between 470 and 950 nm. Our results support the previous finding that tar balls may play an important role in global warming. Due to the non-negligible absorption of tar balls in the near-infrared region, the absorption measured in the field at near-infrared wavelengths cannot solely be due to soot particles.

Global Identification and Characterization of Transcriptionally Active Regions in the Rice Genome

PubMed Central

Stolc, Viktor; Deng, Wei; He, Hang; Korbel, Jan; Chen, Xuewei; Tongprasit, Waraporn; Ronald, Pamela; Chen, Runsheng; Gerstein, Mark; Wang Deng, Xing

2007-01-01

Genome tiling microarray studies have consistently documented rich transcriptional activity beyond the annotated genes. However, systematic characterization and transcriptional profiling of the putative novel transcripts on the genome scale are still lacking. We report here the identification of 25,352 and 27,744 transcriptionally active regions (TARs) not encoded by annotated exons in the rice (Oryza. sativa) subspecies japonica and indica, respectively. The non-exonic TARs account for approximately two thirds of the total TARs detected by tiling arrays and represent transcripts likely conserved between japonica and indica. Transcription of 21,018 (83%) japonica non-exonic TARs was verified through expression profiling in 10 tissue types using a re-array in which annotated genes and TARs were each represented by five independent probes. Subsequent analyses indicate that about 80% of the japonica TARs that were not assigned to annotated exons can be assigned to various putatively functional or structural elements of the rice genome, including splice variants, uncharacterized portions of incompletely annotated genes, antisense transcripts, duplicated gene fragments, and potential non-coding RNAs. These results provide a systematic characterization of non-exonic transcripts in rice and thus expand the current view of the complexity and dynamics of the rice transcriptome. PMID:17372628

Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Xin-Hong; Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan; Lv, Xin-Quan

2014-03-28

Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cellsmore » and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression.« less

Comparative Evaluation of Gemcabene and PPAR Ligands in Transcriptional Assays of Peroxisome Proliferator-Activated Receptors: Implication for the Treatment of Hyperlipidemia and Cardiovascular Disease.

PubMed

Bisgaier, Charles L; Oniciu, Daniela C; Srivastava, Rai Ajit K

2018-03-21

Gemcabene, a late-stage clinical candidate, has shown efficacy for LDL-C, non-HDL cholesterol, apoB, triglycerides and hsCRP reduction, all risk factors for cardiovascular disease (CVD). In rodents, gemcabene showed changes in targets, including apoC-III, apoA-I, peroxisomal enzymes, considered regulated via PPAR gene activation, suggesting a PPAR-mediated mechanism of action for the observed hypolipidemic effects observed in rodents and humans. In the current study, the gemcabene agonist activity against PPAR subtypes of human, rat and mouse were compared to known lipid lowering PPAR activators. Surprisingly, gemcabene showed no or little PPAR-α transactivation compared with reference agonists, which showed concentration-dependent transactivation against human PPAR-α of 2.4 to 30-fold (fenofibric acid), 17-fold (GW590735), and 2.3 to 25-fold (WY14643). These agents also showed robust transactivation of mouse and rat PPAR-α in a concentration-dependent manner. The known PPAR-δ agonists, GW1516, L165041 and GW0742, showed potent agonist activity against human, mouse and rat receptors (ranging from 165- to 396-fold). In contrast, gemcabene at the highest concentration tested (300 µM) showed no response in mouse and rat and a marginal response against human PPAR-δ receptors (3.2-fold). For PPAR-γ, gemcabene showed no agonist activity against all 3 species at 100 µM and marginal activity (3.6-5 fold) at 300 µM. In contrast, the known agonists, rosiglitazone, indomethacin and muraglitazar showed strong activation against the mouse, rat and human PPAR-γ receptors. No clear antagonist activity was observed with gemcabene against any PPAR-subtypes for all 3 species over a wide range of concentrations. In summary, the transactivation studies rule out gemcabene as a direct agonist or antagonist of PPAR-α, PPAR-γ, and PPAR-δ receptors of these three species. These data suggest that the peroxisomal effects observed in rodents and the lipid regulating effects observed in rodents and humans are not related to a direct activation of PPAR receptors by gemcabene.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Optical, Physical and Chemical Properties of Tar Balls Observed During the Yosemite Aerosol Characterization Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hand, Jenny L.; Malm, W. C.; Laskin, Alexander

2005-11-09

The Yosemite Aerosol Characterization Study of summer 2002 (YACS) occurred during an active fire season in the western U. S., and provided an opportunity to investigate many unresolved issues related to the radiative effects of biomass burning aerosols. Single particle analysis was performed on field collected aerosol samples using an array of electron microscopy techniques. Amorphous carbon spheres, or “tar balls”, were present in samples collected during episodes of high particle light scattering coefficients that occurred during the peak of a smoke/haze event. The highest concentrations of light-absorbing carbon from a dual-wavelength aethalometer (λ = 370 and 880 nm) occurredmore » during periods when the particles were predominantly tar balls, indicating they do absorb light in the UV and near-IR range of the solar spectrum. Closure experiments of mass concentrations and light scattering coefficients during periods dominated by tar balls did not require any distinct assumptions of organic carbon molecular weight correction factors, density, or refractive index compared to periods dominated by other types of organic carbon aerosols. Measurements of the hygroscopic behavior of tar balls using an environmental SEM indicate that tar balls do not exhibit deliquescence, but do uptake some water at high (~83 %) relative humidity. The ability of tar balls to efficiently scatter and absorb light, and to absorb water has important implications for their role in regional haze and climate fence.« less

TRICHOME AND ARTEMISININ REGULATOR 1 Is Required for Trichome Development and Artemisinin Biosynthesis in Artemisia annua.

PubMed

Tan, Hexin; Xiao, Ling; Gao, Shouhong; Li, Qing; Chen, Junfeng; Xiao, Ying; Ji, Qian; Chen, Ruibing; Chen, Wansheng; Zhang, Lei

2015-09-01

Trichomes, small protrusions on the surface of many plant species, can produce and store various secondary metabolic products. Artemisinin, the most famous and potent medicine for malaria, is synthesized, stored, and secreted by Artemisia annua trichomes. However, the molecular basis regulating the biosynthesis of artemisinin and the development of trichomes in A. annua remains poorly understood. Here, we report that an AP2 transcription factor, TRICHOME AND ARTEMISININ REGULATOR 1 (TAR1), plays crucial roles in regulating the development of trichomes and the biosynthesis of artemisinin in A. annua. TAR1, which encodes a protein specially located in the nucleus, is mainly expressed in young leaves, flower buds, and some trichomes. In TAR1-RNAi lines, the morphology of trichomes and the composition of cuticular wax were altered, and the artemisinin content was dramatically reduced, which could be significantly increased by TAR1 oeverexpression. Expression levels of several key genes that are involved in artemisinin biosynthesis were altered when TAR1 was silenced or overexpressed. By the electrophoretic mobility shift, yeast one-hybrid and transient transformation β-glucuronidase assays, we showed that ADS and CYP71AV1, two key genes in the biosynthesis pathway of artemisinin, are likely the direct targets of TAR1. Taken together, our results indicate that TAR1 is a key component of the molecular network regulating trichome development and artemisinin biosynthesis in A. annua. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Ubiquitous tar balls with a California-source signature on the shorelines of Prince William Sound, Alaska

USGS Publications Warehouse

Kvenvolden, K.A.; Hostettler, F.D.; Carlson, P.R.; Rapp, J.B.; Threlkeld, C.N.; Warden, A.

1995-01-01

Although the shorelines of Prince William Sound still bear traces of the 1989 Exxon Valdez oil spill, most of the flattened tar balls that can be found today on these shorelines are not residues of Exxon Valdez oil. Instead, the carbon-isotopic and hydrocarbon-biomarker signatures of 61 tar ball samples, collected from shorelines throughout the northern and western parts of the sound, are all remarkably similar and have characteristics consistent with those of oil products that originated from the Monterey Formation source rocks of California. The carbon-isotopic compositions of the tar balls are all closely grouped (??13CPDB = -23.7 ?? 0.2???), within the range found in crude oils from those rocks, but are distinct from isotopic compositions of 28 samples of residues from the Exxon Valdez oil spill (??13CPDB = -29.4 ?? 0.1???). Likewise, values for selected biomarker ratios in the tar balls are all similar but distinct from values of residues from the 1989 oil spill. Carbon-isotopic and biomarker signatures generally relate the tar balls to oil products used in Alaska before ???1970 for construction and pavements. How these tar balls with such similar geochemical characteristics became so widely dispersed throughout the northern and western parts of the sound is not known with certainty, but the great 1964 Alaska earthquake was undoubtedly an important trigger, causing spills from ruptured storage facilities of California-sourced asphalt and fuel oil into Prince William Sound.

Ripples and Dunes in Proctor Crater

NASA Image and Video Library

2017-10-09

NASA's Mars Reconnaissance Rover (MRO) has observed two types of wind (aeolian) features in Proctor Crater: large, dark features that are sand dunes, made up of basaltic particles, and smaller, light-toned ripples that we call "TAR," or "transverse aeolian ridges." The origin of the TARs is a mystery. They might be dust deposits, or perhaps coarse grained ripples that are coated in bright dust. These TARs are less than 10 meters tall, and are much smaller than the sand dunes that reach impressive heights of over 130 meters. In other places on Mars, TARs are generally older than sand dunes, but here in Proctor Crater, it is not so obvious. How can we tell which came first, the TARs or the dunes? The dunes are situated on top of the TARs, and with this information, we can say the dunes are clearly the younger formations here in Proctor Crater. Fortunately, HiRISE has a tool that can solve this riddle. By taking stereo images of the same region from two different locations, we can estimate the topography of the region by measuring the displacement of surface features from one picture to the other. The result is a quantitative estimate of the local surface topography, called a digital terrain model. The dunes are situated on top of the TARs, and with this information, we can say the dunes are clearly the younger formations here in Proctor Crater. https://photojournal.jpl.nasa.gov/catalog/PIA22040

Slowdown of Interhelical Motions Induces a Glass Transition in RNA

PubMed Central

Frank, Aaron T.; Zhang, Qi; Al-Hashimi, Hashim M.; Andricioaei, Ioan

2015-01-01

RNA function depends crucially on the details of its dynamics. The simplest RNA dynamical unit is a two-way interhelical junction. Here, for such a unit—the transactivation response RNA element—we present evidence from molecular dynamics simulations, supported by nuclear magnetic resonance relaxation experiments, for a dynamical transition near 230 K. This glass transition arises from the freezing out of collective interhelical motional modes. The motions, resolved with site-specificity, are dynamically heterogeneous and exhibit non-Arrhenius relaxation. The microscopic origin of the glass transition is a low-dimensional, slow manifold consisting largely of the Euler angles describing interhelical reorientation. Principal component analysis over a range of temperatures covering the glass transition shows that the abrupt slowdown of motion finds its explanation in a localization transition that traps probability density into several disconnected conformational pools over the low-dimensional energy landscape. Upon temperature increase, the probability density pools then flood a larger basin, akin to a lakes-to-sea transition. Simulations on transactivation response RNA are also used to backcalculate inelastic neutron scattering data that match previous inelastic neutron scattering measurements on larger and more complex RNA structures and which, upon normalization, give temperature-dependent fluctuation profiles that overlap onto a glass transition curve that is quasi-universal over a range of systems and techniques. PMID:26083927

RelAp43, a member of the NF-κB family involved in innate immune response against Lyssavirus infection.

PubMed

Luco, Sophie; Delmas, Olivier; Vidalain, Pierre-Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

2012-01-01

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.

RelAp43, a Member of the NF-κB Family Involved in Innate Immune Response against Lyssavirus Infection

PubMed Central

Vidalain, Pierre-Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

2012-01-01

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response. PMID:23271966

The coactivator CBP stimulates human T-cell lymphotrophic virus type I Tax transactivation in vitro.

PubMed

Kashanchi, F; Duvall, J F; Kwok, R P; Lundblad, J R; Goodman, R H; Brady, J N

1998-12-18

Tax interacts with the cellular cyclic AMP-responsive element binding protein (CREB) and facilitates the binding of the coactivator CREB binding protein (CBP), forming a multimeric complex on the cyclic AMP-responsive element (CRE)-like sites in the human T-cell lymphotrophic virus type I (HTLV-I) promoter. The trimeric complex is believed to recruit additional regulatory proteins to the HTLV-I long terminal repeat, but there has been no direct evidence that CBP is required for Tax-mediated transactivation. We present evidence that Tax and CBP activate transcription from the HTLV-I 21 base pair repeats on naked DNA templates. Transcriptional activation of the HTLV-I sequences required both Tax and CBP and could be mediated by either the N-terminal activation domain of CBP or the full-length protein. Fluorescence polarization binding assays indicated that CBP does not markedly enhance the affinity of Tax for the trimeric complex. Transcription analyses suggest that CBP activates Tax-dependent transcription by promoting transcriptional initiation and reinitiation. The ability of CBP to activate the HTLV-I promoter does not involve the stabilization of Tax binding, but rather depends upon gene activation properties of the co-activator that function in the context of a naked DNA template.

The nature and molecular basis of cutaneous photosensitivity reactions to psoralens and coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pathak, M.A.; Joshi, P.C.

1983-06-01

The basic aspects of cutaneous photosensitization reactions and the mode of therapeutic effectiveness of psoralens and coal tar, the two groups of photosensitizing agents used extensively in the photochemotherapy of psoriasis, have been reviewed. Psoralen-induced skin photosensitization and the therapeutic action of psoralens involve two distinct types of reactions, and these two reactions occur independently of each other and concurrently when the psoralen-treated skin (oral or topical) is exposed to 320 to 400 nm of radiation. The first, type I, is an oxygen-independent reaction and primarily involves photoreaction with DNA; the second, type II, is a sensitized reaction dependent onmore » oxygen and involves the formation of singlet oxygen (1O2). The photoreactive form of psoralen is its triplet state, and the sites of reaction are (1) the cell membrane of the epidermal, dermal, and endothelial cells; (2) the cytoplasmic constituents, such as enzymes, RNA, lysosomes, etc.; (3) the cell nuclei (DNA and chromatin); and (4) the sensitized production of 1O2, which is responsible for cell-membrane damage and vasodilation. The major damage would be initiated by a type I reaction and would be seen in the form of nuclear damage to DNA resulting from the interaction of psoralen with DNA and to a lesser extent with RNA. The skin photosensitization response (erythema, edema, membrane damage, etc.) would result from a type II reaction involving the generation of 1O2. Crude coal tar (CCT), widely used in the Goeckerman therapy for psoriasis, also produces type I and type II reactions. The therapeutic and photosensitizing actions of CCT are due to (1) the photoconjugation of the photoreactive ingredients of CCT with DNA, causing interstrand cross-links; and (2) the production of 1O2. CCT is an efficient producer of 1O2, more so than 8-methoxypsoralen, and is responsible for cell-membrane damage and cellular edema.« less

Thermal Cracking of Tars in a Continuously Fed Reactor with Steam

DTIC Science & Technology

2011-05-01

Fluidized Bed using biomass 8 Tars  Mixture of organic components present in gasification product gas with high molecular weight hydrocarbons [MW...Disable sulfur removal systems FoulingPlugging [Ref. 3: Biomass Gasification – Tar and Particles in Product Gases Sampling and Analysis”, European...P., and Nussbaumer T., “Gas Cleaning Requirements for Internal Combustion Engine Applications of Fixed Bed Biomass Gasification ”, Biomass and

Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002

PubMed Central

2011-01-01

Background Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event. Methods The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors. Results In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake. Conclusions The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction. PMID:21542909

Ecological risk assessment of elemental pollution in sediment from Tunku Abdul Rahman National Park, Sabah

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elias, Md Suhaimi; Hamzah, Mohd Suhaimi; Rahman, Shamsiah Ab

Eleven (11) surface sediment samples were collected from Tunku Abdul Rahman National Park, Sabah. The neutron activation analysis (NAA) and inductively coupled plasma-mass spectrometry (ICP-MS) techniques were applied for the determinations metal contents and their distributions in sediment samples. The results shown that Arsenic (As) concentrations are enriched at all sampling stations except for station TAR 09, with enrichment factor (EF) values ranged from 1.1 to 7.2. The elements such as Cd, Cr, Sb and U showed enrichment at a few stations and other elements (Cr, Cu, Pb, Th, Zn) shown as background levels in all stations. Degrees of contaminationmore » in this study were calculated base on concentrations of six elements (As, Cd, Cr, Cu, Pb, and Zn). TAR 11 station can be categorized as very high degree of contamination with degree of contamination value of 43.2. TAR 07 station can be categorized as a considerable degree of contamination (contamination value of 16.9). Six stations (TAR 01, 03, 04, 05, 06, 08, 10) showed moderate degree of contamination, with contamination values ranging from 8.0 to 16.0. TAR 02 and TAR 09 stations showed low degree of contaminations (< 8.0). TAR 11 showed very high ecological risk index (R{sub I}) with RI value is 916. TAR 07 and TAR 10 showed moderate ecological risk index with R{sub I} value 263 and 213, respectively. Other stations showed low ecological risk with RI values ranging from 42.3 to 117 (< 150). Very high ecological risk index could give an adverse effect to the benthic organism. The data obtained from the enrichment factor, degree of contamination and ecological risk index provided vital information, which can be used for future comparison. Information from the present study will be useful to the relevant government agencies and authorities in preparing preventive action to control direct discharge of heavy metals from industries, agro-base activities and domestic waste to the rivers and the sea.« less

Analysis of pure tar substances (polycyclic aromatic hydrocarbons) in the gas stream using ultraviolet visible (UV-Vis) spectroscopy and multivariate curve resolution (MCR).

PubMed

Weide, Tobias; Guschin, Viktor; Becker, Wolfgang; Koelle, Sabine; Maier, Simon; Seidelt, Stephan

2015-01-01

The analysis of tar, mostly characterized as polycyclic aromatic hydrocarbons (PAHs), describes a topic that has been researched for years. An online analysis of tar in the gas stream in particular is needed to characterize the tar conversion or formation in the biomass gasification process. The online analysis in the gas is carried out with ultraviolet-visible (UV-Vis) spectroscopy (190-720 nm). This online analysis is performed with a measuring cell developed by the Fraunhofer Institute for Chemical Technology (ICT). To this day, online tar measurements using UV-Vis spectroscopy have not been carried out in detail. Therefore, PAHs are analyzed as follows. The measurements are split into different steps. The first step to prove the online method is to vaporize single tar substances. These experiments show that a qualitative analysis of PAHs in the gas stream with the used measurement setup is possible. Furthermore, it is shown that the method provides very exact results, so that a differentiation of various PAHs is possible. The next step is to vaporize a PAH mixture. This step consists of vaporizing five pure substances almost simultaneously. The interpretation of the resulting data is made using a chemometric interpretation method, the multivariate curve resolution (MCR). The verification of the calculated results is the main aim of this experiment. It has been shown that the tar mixture can be analyzed qualitatively and quantitatively (in arbitrary units) in detail using the MCR. Finally it is the main goal of this paper to show the first steps in the applicability of the UV-Vis spectroscopy and the measurement setup on online tar analysis in view of characterizing the biomass gasification process. Due to that, the gasification plant (at the laboratory scale), developed and constructed by the Fraunhofer ICT, has been used to vaporize these substances. Using this gasification plant for the experiments enables the usage of the measurement setup also for the spectroscopic analysis of the tar formation during the biomass gasification.

Technology for the production of Zero Q.I pitch from coal tar

NASA Astrophysics Data System (ADS)

Karthik, K.; Kumar, K. Rajesh; Rao, C. V. Nageswara; Kumar, B. Vinod; Murty, J. V. S.

2013-06-01

Zero Quinoline Insolubles (Q.I) pitch is a special type of pitch obtained from pre-treatment of coal tar, which is converted into pitch. This is used for impregnation of electrodes for improving the strength, electrical properties and also used as a pre-cursor for Mesophase pitch for producing Mesophase pitch based carbon fibers, carbon foam, and Meso carbon micro beads. This paper discusses the technology of Q.I separation from Coal Tar by using decantation of Coal Tar mixed with Heavy Creosote Oil (HC Oil) at different temperatures. By this method we were able to produce the Zero Q.I pitch with a Q.I value of 0.1%.

Arabidopsis basic leucine zipper transcription factors involved in an abscisic acid-dependent signal transduction pathway under drought and high-salinity conditions

PubMed Central

Uno, Yuichi; Furihata, Takashi; Abe, Hiroshi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2000-01-01

The induction of the dehydration-responsive Arabidopsis gene, rd29B, is mediated mainly by abscisic acid (ABA). Promoter analysis of rd29B indicated that two ABA-responsive elements (ABREs) are required for the dehydration-responsive expression of rd29B as cis-acting elements. Three cDNAs encoding basic leucine zipper (bZIP)-type ABRE-binding proteins were isolated by using the yeast one-hybrid system and were designated AREB1, AREB2, and AREB3 (ABA-responsive element binding protein). Transcription of the AREB1 and AREB2 genes is up-regulated by drought, NaCl, and ABA treatment in vegetative tissues. In a transient transactivation experiment using Arabidopsis leaf protoplasts, both the AREB1 and AREB2 proteins activated transcription of a reporter gene driven by ABRE. AREB1 and AREB2 required ABA for their activation, because their transactivation activities were repressed in aba2 and abi1 mutants and enhanced in an era1 mutant. Activation of AREBs by ABA was suppressed by protein kinase inhibitors. These results suggest that both AREB1 and AREB2 function as transcriptional activators in the ABA-inducible expression of rd29B, and further that ABA-dependent posttranscriptional activation of AREB1 and AREB2, probably by phosphorylation, is necessary for their maximum activation by ABA. Using cultured Arabidopsis cells, we demonstrated that a specific ABA-activated protein kinase of 42-kDa phosphorylated conserved N-terminal regions in the AREB proteins. PMID:11005831

Arabidopsis basic leucine zipper transcription factors involved in an abscisic acid-dependent signal transduction pathway under drought and high-salinity conditions.

PubMed

Uno, Y; Furihata, T; Abe, H; Yoshida, R; Shinozaki, K; Yamaguchi-Shinozaki, K

2000-10-10

The induction of the dehydration-responsive Arabidopsis gene, rd29B, is mediated mainly by abscisic acid (ABA). Promoter analysis of rd29B indicated that two ABA-responsive elements (ABREs) are required for the dehydration-responsive expression of rd29B as cis-acting elements. Three cDNAs encoding basic leucine zipper (bZIP)-type ABRE-binding proteins were isolated by using the yeast one-hybrid system and were designated AREB1, AREB2, and AREB3 (ABA-responsive element binding protein). Transcription of the AREB1 and AREB2 genes is up-regulated by drought, NaCl, and ABA treatment in vegetative tissues. In a transient transactivation experiment using Arabidopsis leaf protoplasts, both the AREB1 and AREB2 proteins activated transcription of a reporter gene driven by ABRE. AREB1 and AREB2 required ABA for their activation, because their transactivation activities were repressed in aba2 and abi1 mutants and enhanced in an era1 mutant. Activation of AREBs by ABA was suppressed by protein kinase inhibitors. These results suggest that both AREB1 and AREB2 function as transcriptional activators in the ABA-inducible expression of rd29B, and further that ABA-dependent posttranscriptional activation of AREB1 and AREB2, probably by phosphorylation, is necessary for their maximum activation by ABA. Using cultured Arabidopsis cells, we demonstrated that a specific ABA-activated protein kinase of 42-kDa phosphorylated conserved N-terminal regions in the AREB proteins.

Local tissue air ratio in an anatomic phantom for 60Co total body irradiation.

PubMed

Vrtar, M; Purisić, A

1991-07-01

Tissue-air ratio (TAR), as the basic dosimetric function, is not ideally applicable to all important locations in total body irradiation (TBI) dosimetry because it generally refers to central ray measurements. We therefore introduced the local TAR which depends on the specific distribution of the scattering centres around the location of interest. Local TAR measurements were performed in an anatomic water phantom, produced by a sculptor, representing a patient during TBI in the real treatment position. A comparison has been made between TAR values, defined on the beam's ray at different locations in the anatomic phantom and cubic phantoms of different size. The local TAR values in the anatomic phantom, having more realistic outer surface curvatures, are lower by a few percent in most locations. We consider these values more accurate and better applicable to TBI conditions than those obtained in cubic water phantoms, even if the volume of the phantom is adapted to the particular side of the body.

The contribution of low tar cigarettes to environmental tobacco smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chortyk, O.T.; Schlotzhauer, W.S.

A series of low tar cigarettes (LTC) were smoked and the quantities of condensable mainstream (inhaled) and sidestream (between puffs) smoke compounds were determined and compared to those produced by a high tar, nonfilter cigarette. It was found that the LTC produced large quantities of sidestream smoke condensates, about equal to the high tar cigarette, and contained very high levels of toxic or cocarcinogenic phenols. On an equal weight basis, the LTC emitted more of these hazardous compounds into sidestream and environmental tobacco smoke. Higher smoke yields of a flavor additive and a sugar degradation product indicated addition of suchmore » compounds during the manufacture of LTC. It was concluded that, compared to a high tar cigarette, smoking LTC may be better for the smoker, but not for the nearby nonsmoker. Information should be developed to allow smokers to choose LTC that produce lower levels of hazardous compounds in their environmentally emitted sidestream smoke.« less

Identification of sources of tar balls deposited along the Goa coast, India, using fingerprinting techniques.

PubMed

Suneel, V; Vethamony, P; Zakaria, M P; Naik, B G; Prasad, K V S R

2013-05-15

Deposition of tar balls along the coast of Goa, India is a common phenomenon during the southwest monsoon. Representative tar ball samples collected from various beaches of Goa and one Bombay High (BH) crude oil sample were subjected to fingerprint analysis based on diagnostic ratios of n-alkane, biomarkers of pentacyclic tri-terpanes and compound specific stable carbon isotope (δ¹³C) analysis to confirm the source. The results were compared with the published data of Middle East Crude Oil (MECO) and South East Asian Crude Oil (SEACO). The results revealed that the tar balls were from tanker-wash derived spills. The study also confirmed that the source is not the BH, but SEACO. The present study suggests that the biomarkers of alkanes and hopanes coupled with stable carbon isotope analysis act as a powerful tool for tracing the source of tar balls, particularly when the source specific biomarkers fail to distinguish the source. Copyright © 2013 Elsevier Ltd. All rights reserved.

The intrinsically disordered C-terminal region of Arabidopsis thaliana TCP8 transcription factor acts both as a transactivation and self-assembly domain.

PubMed

Valsecchi, Isabel; Guittard-Crilat, Emilie; Maldiney, Régis; Habricot, Yvette; Lignon, Sabrina; Lebrun, Régine; Miginiac, Emile; Ruelland, Eric; Jeannette, Emmanuelle; Lebreton, Sandrine

2013-09-01

TCPs are plant specific transcription factors with non-canonical basic helix-loop-helix domains. While Arabidopsis thaliana has 24 TCPs involved in cell proliferation and differentiation, their mode of action has not been fully elucidated. Using bioinformatic tools, we demonstrate that TCP transcription factors belong to the intrinsically disordered proteins (IDP) family and that disorder is higher in class I TCPs than in class II TCPs. In particular, using bioinformatic and biochemical approaches, we have characterized TCP8, a class I TCP. TCP8 exhibits three intrinsically disordered regions (IDR) made of more than 50 consecutive residues, in which phosphorylable Ser residues are mainly clustered. Phosphorylation of Ser-211 that belongs to the central IDR was confirmed by mass spectrometry. Yeast two-hybrid assays also showed that the C-terminal IDR corresponds to a transactivation domain. Moreover, biochemical experiments demonstrated that TCP8 tends to oligomerize in dimers, trimers and higher-order multimers. Bimolecular fluorescence complementation (BiFC) experiments carried out on a truncated form of TCP8 lacking the C-terminal IDR indicated that it is effectively required for the pronounced self-assembly of TCP8. These data were reinforced by the prediction of a coiled coil domain in this IDR. The C-terminal IDR acts thus as an oligomerization domain and also a transactivation domain. Moreover, many Molecular Recognition Features (MoRFs) were predicted, indicating that TCP8 could interact with several partners to fulfill a fine regulation of transcription in response to various stimuli.

Estrogen receptor β (ERβ1) transactivation is differentially modulated by the transcriptional coregulator Tip60 in a cis-acting element-dependent manner.

PubMed

Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

2013-08-30

Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1.

Estrogen Receptor β (ERβ1) Transactivation Is Differentially Modulated by the Transcriptional Coregulator Tip60 in a cis-Acting Element-dependent Manner*

PubMed Central

Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

2013-01-01

Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1. PMID:23857583

Transactivation potencies of Baikal seal constitutive active/androstane receptor by persistent organic pollutants and brominated flame retardants.

PubMed

Sakai, Hiroki; Kim, Eun-Young; Petrov, Evgeny A; Tanabe, Shinsuke; Iwata, Hisato

2009-08-15

To characterize ligand-dependent transcriptional activation of constitutive active/androstane receptor (CAR) in aquatic mammals, transactivation potentials of the Baikal seal (Pusa sibirica) CAR (bsCAR) by environmental pollutants, including persistent organic pollutants (POPs) and brominated flame retardants (BFRs), were investigated using an in vitro reporter gene assay, and compared with those of the mouse CAR (mCAR). Measurement of luciferase reporter gene activities demonstrated that the seal CAR was activated by POPs, including a technical mixture of PCBs (Kanechlor-500), certain individual PCB congeners, DDT compounds, and trans-nonachlor. No or slight bsCAR-dependent activity was detected in experiments with PBDE congeners and HBCDs. The interspecies comparison of lowest observed effect concentration (LOEC) for CAR transactivation byeach compound revealed that bsCAR responds more sensitively to PCBs than mCAR. In addition, bsCAR was weakly deactivated by PBDE99, whereas mCAR transcriptional activity decreased weakly by PBDE100, PBDE154, and PBDE187. Comparison of reporter gene activities by the congeners with the same IUPAC numbers among PCBs and PBDEs revealed that both bsCAR and mCAR were not activated by PBDE99 and PBDE153, but were activated by PCB99 and PCB153. The small ligand-binding pocket in CAR may contribute to difference in response between PCBs and PBDEs. Given that ethical rationale prevents dosing studies with such organohalogens in aquatic mammals, our in vitro assay system constructed with CAR cDNA from a species of interest provides a useful and realistic alternative approach in ecotoxicology.

The Role of Ethylene and Cold Temperature in the Regulation of the Apple POLYGALACTURONASE1 Gene and Fruit Softening1[W][OA

PubMed Central

Tacken, Emma; Ireland, Hilary; Gunaseelan, Kularajathevan; Karunairetnam, Sakuntala; Wang, Daisy; Schultz, Keith; Bowen, Judith; Atkinson, Ross G.; Johnston, Jason W.; Putterill, Jo; Hellens, Roger P.; Schaffer, Robert J.

2010-01-01

Fruit softening in apple (Malus × domestica) is associated with an increase in the ripening hormone ethylene. Here, we show that in cv Royal Gala apples that have the ethylene biosynthetic gene ACC OXIDASE1 suppressed, a cold treatment preconditions the apples to soften independently of added ethylene. When a cold treatment is followed by an ethylene treatment, a more rapid softening occurs than in apples that have not had a cold treatment. Apple fruit softening has been associated with the increase in the expression of cell wall hydrolase genes. One such gene, POLYGALACTURONASE1 (PG1), increases in expression both with ethylene and following a cold treatment. Transcriptional regulation of PG1 through the ethylene pathway is likely to be through an ETHYLENE-INSENSITIVE3-like transcription factor, which increases in expression during apple fruit development and transactivates the PG1 promoter in transient assays in the presence of ethylene. A cold-related gene that resembles a COLD BINDING FACTOR (CBF) class of gene also transactivates the PG1 promoter. The transactivation by the CBF-like gene is greatly enhanced by the addition of exogenous ethylene. These observations give a possible molecular mechanism for the cold- and ethylene-regulated control of fruit softening and suggest that either these two pathways act independently and synergistically with each other or cold enhances the ethylene response such that background levels of ethylene in the ethylene-suppressed apples is sufficient to induce fruit softening in apples. PMID:20237022

The Transmodulation of HER2 and EGFR by Substance P in Breast Cancer Cells Requires c-Src and Metalloproteinase Activation.

PubMed

Garcia-Recio, Susana; Pastor-Arroyo, Eva M; Marín-Aguilera, Mercedes; Almendro, Vanessa; Gascón, Pedro

2015-01-01

Substance P (SP) is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC) aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R) signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator) and of metalloproteinases (ligand-dependent mediators) in HER2/EGFR activation. Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines. Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process.

Treating tar sands formations with dolomite

DOEpatents

Vinegar, Harold J.; Karanikas, John Michael

2010-06-08

Methods for treating a tar sands formation are described herein. The tar sands formation may include dolomite and hydrocarbons. Methods may include providing heat at less than the decomposition temperature of dolomite from one or more heaters to at least a portion of the formation. At least some of the hydrocarbon fluids are mobilized in the formation. At least some of the hydrocarbon fluids may be produced from the formation.

A photographic method for estimating wear of coal tar sealcoat from parking lots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mateo Scoggins; Tom Ennis; Nathan Parker

2009-07-01

Coal-tar-based sealcoat has been recognized as an important source of PAHs to the environment through wear and transport via stormwater runoff. Sealcoat removal rates have not been measured or even estimated in the literature due to the complex array of physical and chemical process involved. A photographic study was conducted that incorporates all sources of wear using 10 coal tar-sealed parking lots in Austin, Texas, with sealcoat age ranging from 0 to 5 years. Randomly located photographs from each parking lot were analyzed digitally to quantify black sealed areas versus lighter colored unsealed areas at the pixel level. The resultsmore » indicate that coal tar sealcoat wears off of the driving areas of parking lots at a rate of approximately 4.7% per year, and from the parking areas of the lots at a rate of approximately 1.4% per year. The overall annual loss of sealcoat was calculated at 2.4%. This results in an annual delivery to the environment of 0.51 g of PAHs per m{sup 2} of coal tar-sealed parking lot. These values provide a more robust and much higher estimate of loading of PAHs from coal tar sealcoated parking lots when compared to other available measures. 20 refs., 6 figs.« less

The linear relationship between cigarette tar and nicotine yields: regulatory implications for smoke constituent ratios.

PubMed

St Charles, F K; Cook, C J; Clayton, P M

2011-02-01

Cigarette smoke analyte yields are often expressed as ratios relative to tar or nicotine yields, usually to compare different products or to estimate human uptake of smoke in relation to nicotine uptake measurements. The method, however, can lead to distorted interpretations, especially in the case of ratios from ultra-low tar yield cigarettes. In brief, as tar yields decrease below the 5–6 mg per cigarette range, the tar-to-nicotine ratio (TNR) decreases rapidly in a non-linear fashion. If, however, the nicotine yield, rather than the ratio, is plotted versus the tar yield, the non-linearity disappears and a straight line is obtained, with a slight positive intercept for nicotine on the ordinate. Unlike the ratio, the slope appears to depend only on the concentration of the nicotine in the blend and does not appear to vary with smoking parameters such as puff volume, puff interval or length smoked or with cigarette design parameters such as length, circumference or the amount of filtration or filter ventilation. Therefore, such a slope is analogous to the TNR although, unlike that ratio, it is invariant. Even more simply, the concentration of the nicotine in the blend, at least for American blend-style cigarettes, provides a similar index.

Pavement Sealcoat, PAHs, and the Environment

NASA Astrophysics Data System (ADS)

Van Metre, P. C.; Mahler, B. J.

2011-12-01

Recent research by the USGS has identified coal-tar-based pavement sealants as a major source of polycyclic aromatic hydrocarbons (PAHs) to the environment. Coal-tar-based sealcoat is commonly used to coat parking lots and driveways and is typically is 20-35 percent coal tar pitch, a known human carcinogen. Several PAHs are suspected mutagens, carcinogens, and (or) teratogens. In the central and eastern U.S. where the coal-tar-based sealants dominate use, sum-PAH concentration in dust particles from sealcoated pavement is about 1,000 times higher than in the western U.S. where the asphalt-based formulation is prevalent. Source apportionment modeling indicates that particles from sealcoated pavement are contributing the majority of the PAHs to recent lake sediment in 35 U.S. urban lakes and are the primary cause of upward trends in PAHs in many of these lakes. Mobile particles from parking lots with coal-tar-based sealcoat are tracked indoors, resulting in elevated PAH concentrations in house dust. In a recently completed study, volatilization fluxes of PAHs from sealcoated pavement were estimated to be about 60 times fluxes from unsealed pavement. Using a wide variety of methods, the author and colleagues have shown that coal-tar-based sealcoat is a major source of PAHs to the urban environment and might pose risks to aquatic life and human health.

Pyrolysis characteristics and kinetics of acid tar waste from crude benzol refining: A thermogravimetry-mass spectrometry analysis.

PubMed

Chihobo, Chido H; Chowdhury, Arindrajit; Kuipa, Pardon K; Simbi, David J

2016-12-01

Pyrolysis is an attractive thermochemical conversion technology that may be utilised as a safe disposal option for acid tar waste. The kinetics of acid tar pyrolysis were investigated using thermogravimetry coupled with mass spectrometry under a nitrogen atmosphere at different heating rates of 10, 15 and 20 K min -1 The thermogravimetric analysis shows three major reaction peaks centred around 178 °C, 258 °C, and 336 °C corresponding to the successive degradation of water soluble lower molecular mass sulphonic acids, sulphonated high molecular mass hydrocarbons, and high molecular mass hydrocarbons. The kinetic parameters were evaluated using the iso-conversional Kissinger-Akahira-Sunose method. A variation in the activation energy with conversion revealed that the pyrolysis of the acid tar waste progresses through complex multi-step kinetics. Mass spectrometry results revealed a predominance of gases such as hydrogen, methane and carbon monoxide, implying that the pyrolysis of acid tar waste is potentially an energy source. Thus the pyrolysis of acid tar waste may present a viable option for its environmental treatment. There are however, some limitations imposed by the co-evolution of corrosive gaseous components for which appropriate considerations must be provided in both pyrolysis reactor design and selection of construction materials. © The Author(s) 2016.

Functional analysis of a Wheat Homeodomain protein, TaR1, reveals that host chromatin remodelling influences the dynamics of the switch to necrotrophic growth in the phytopathogenic fungus Zymoseptoria tritici.

PubMed

Lee, Jack; Orosa, Beatriz; Millyard, Linda; Edwards, Martin; Kanyuka, Kostya; Gatehouse, Angharad; Rudd, Jason; Hammond-Kosack, Kim; Pain, Naomi; Sadanandom, Ari

2015-04-01

A distinguishing feature of Septoria leaf blotch disease in wheat is the long symptomless growth of the fungus amongst host cells followed by a rapid transition to necrotrophic growth resulting in disease lesions. Global reprogramming of host transcription marks this switch to necrotrophic growth. However no information exists on the components that bring about host transcriptional reprogramming. Gene-silencing, confocal-imaging and protein-protein interaction assays where employed to identify a plant homeodomain (PHD) protein, TaR1 in wheat that plays a critical role during the transition from symptomless to necrotrophic growth of Septoria. TaR1-silenced wheat show earlier symptom development upon Septoria infection but reduced fungal sporulation indicating that TaR1 is key for prolonging the symptomless phase and facilitating Septoria asexual reproduction. TaR1 is localized to the nucleus and binds to wheat Histone 3. Trimethylation of Histone 3 at lysine 4 (H3K4) and lysine 36 (H3K36) are found on open chromatin with actively transcribed genes, whereas methylation of H3K27 and H3K9 are associated with repressed loci. TaR1 specifically recognizes dimethylated and trimethylated H3K4 peptides suggesting that it regulates transcriptional activation at open chromatin. We conclude that TaR1 is an important component for the pathogen life cycle in wheat that promotes successful colonization by Septoria. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphey, P. C.; Daitch, D.; Environmental Science Division

In August 2005, the U.S. Congress enacted the Energy Policy Act of 2005, Public Law 109-58. In Section 369 of this Act, also known as the ''Oil Shale, Tar Sands, and Other Strategic Unconventional Fuels Act of 2005,'' Congress declared that oil shale and tar sands (and other unconventional fuels) are strategically important domestic energy resources that should be developed to reduce the nation's growing dependence on oil from politically and economically unstable foreign sources. In addition, Congress declared that both research- and commercial-scale development of oil shale and tar sands should (1) be conducted in an environmentally sound mannermore » using management practices that will minimize potential impacts, (2) occur with an emphasis on sustainability, and (3) benefit the United States while taking into account concerns of the affected states and communities. To support this declaration of policy, Congress directed the Secretary of the Interior to undertake a series of steps, several of which are directly related to the development of a commercial leasing program for oil shale and tar sands. One of these steps was the completion of a programmatic environmental impact statement (PEIS) to analyze the impacts of a commercial leasing program for oil shale and tar sands resources on public lands, with an emphasis on the most geologically prospective lands in Colorado, Utah, and Wyoming. For oil shale, the scope of the PEIS analysis includes public lands within the Green River, Washakie, Uinta, and Piceance Creek Basins. For tar sands, the scope includes Special Tar Sand Areas (STSAs) located in Utah. This paleontological resources overview report was prepared in support of the Oil Shale and Tar Sands Resource Management Plan Amendments to Address Land Use Allocations in Colorado, Utah, and Wyoming and PEIS, and it is intended to be used by Bureau of Land Management (BLM) regional paleontologists and field office staff to support future projectspecific analyses. Additional information about the PEIS can be found at http://ostseis.anl.gov.« less

Co-pyrolysis behaviour and kinetic of two typical solid wastes in China and characterisation of activated carbon prepared from pyrolytic char.

PubMed

Ma, Yuhui; Niu, Ruxuan; Wang, Xiaona; Wang, Qunhui; Wang, Xiaoqiang; Sun, Xiaohong

2014-11-01

This is the first study on the co-pyrolysis of spent substrate of Pleurotus ostreatus and coal tar pitch, and the activated carbon prepared from the pyrolytic char. Thermogravimetry (TG) analysis was carried out taking spent substrate, coal tar pitch and spent substrate-coal tar pitch mixture. The activation energies of pyrolysis reactions were obtained via the Flynn-Wall-Ozawa and Kissinger-Akahira-Sunose methods. The kinetic models were determined by the master-plots method. The activated carbons were characterised by N2-adsorption, Fourier transform infrared spectroscopy and X-ray diffraction. Experimental results demonstrated a synergistic effect happened during co-pyrolysis, which was characterised by a decreased maximum decomposition rate and an enhanced char yield. The average activation energies of the pyrolysis reactions of spent substrate, coal tar pitch and the mixture were 115.94, 72.92 and 94.38 kJ mol(-1) for the Flynn-Wall-Ozawa method, and 112.17, 65.62 and 89.91 kJ mol(-1) for the Kissinger-Akahira-Sunose method. The reaction model functions were f(α) = (1-α)(3.42), (1-α)(1.72) and (1-α)(3.07) for spent substrate, coal tar pitch and the mixture, respectively. The mixture char-derived activated carbon had a Brunauer-Emmett-Teller surface area up to 1337 m(2) g(-1) and a total pore volume of 0.680 cm(3) g(-1). Mixing spent substrate with coal tar pitch led to the creation of more micropores and a higher surface area compared with the single spent substrate and coal tar pitch char. Also, the mixture char-derived activated carbon had a higher proportion of aromatic stacking. This study provides a reference for the utilisation of spent substrate and coal tar pitch via co-pyrolysis, and their pyrolytic char as a promising precursor of activated carbon. © The Author(s) 2014.

Class I cultural resource overview for oil shale and tar sands areas in Colorado, Utah and Wyoming.

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Rourke, D.; Kullen, D.; Gierek, L.

2007-11-01

In August 2005, the U.S. Congress enacted the Energy Policy Act of 2005, Public Law 109-58. In Section 369 of this Act, also known as the 'Oil Shale, Tar Sands, and Other Strategic Unconventional Fuels Act of 2005', Congress declared that oil shale and tar sands (and other unconventional fuels) are strategically important domestic energy resources that should be developed to reduce the nation's growing dependence on oil from politically and economically unstable foreign sources. The Bureau of Land Management (BLM) is developing a Programmatic Environmental Impact Statement (PEIS) to evaluate alternatives for establishing commercial oil shale and tar sandsmore » leasing programs in Colorado, Wyoming, and Utah. This PEIS evaluates the potential impacts of alternatives identifying BLM-administered lands as available for application for commercial leasing of oil shale resources within the three states and of tar sands resources within Utah. The scope of the analysis of the PEIS also includes an assessment of the potential effects of future commercial leasing. This Class I cultural resources study is in support of the Draft Oil Shale and Tar Sands Resource Management Plan Amendments to Address Land Use Allocations in Colorado, Utah, and Wyoming and Programmatic Environmental Impact Statement and is an attempt to synthesize archaeological data covering the most geologically prospective lands for oil shale and tar sands in Colorado, Utah, and Wyoming. This report is based solely on geographic information system (GIS) data held by the Colorado, Utah, and Wyoming State Historic Preservation Offices (SHPOs). The GIS data include the information that the BLM has provided to the SHPOs. The primary purpose of the Class I cultural resources overview is to provide information on the affected environment for the PEIS. Furthermore, this report provides recommendations to support planning decisions and the management of cultural resources that could be impacted by future oil shale and tar sands resource development.« less

Ectopic Expression of Pumpkin NAC Transcription Factor CmNAC1 Improves Multiple Abiotic Stress Tolerance in Arabidopsis

PubMed Central

Cao, Haishun; Wang, Li; Nawaz, Muhammad A.; Niu, Mengliang; Sun, Jingyu; Xie, Junjun; Kong, Qiusheng; Huang, Yuan; Cheng, Fei; Bie, Zhilong

2017-01-01

Drought, cold and salinity are the major environmental stresses that limit agricultural productivity. NAC transcription factors regulate the stress response in plants. Pumpkin (Cucurbita moschata) is an important cucurbit vegetable crop and it has strong resistance to abiotic stress; however, the biological functions of stress-related NAC genes in this crop are largely unknown. This study reports the function of CmNAC1, a stress-responsive pumpkin NAC domain protein. The CmNAC1-GFP fusion protein was transiently expressed in tobacco leaves for subcellular localization analysis, and we found that CmNAC1 is localized in the nucleus. Transactivation assay in yeast cells revealed that CmNAC1 functions as a transcription activator, and its transactivation domain is located in the C-terminus. CmNAC1 was ubiquitously expressed in different organs, and its transcript was induced by salinity, cold, dehydration, H2O2, and abscisic acid (ABA) treatment. Furthermore, the ectopic expression (EE) of CmNAC1 in Arabidopsis led to ABA hypersensitivity and enhanced tolerance to salinity, drought and cold stress. In addition, five ABA-responsive elements were enriched in CmNAC1 promoter. The CmNAC1-EE plants exhibited different root architecture, leaf morphology, and significantly high concentration of ABA compared with WT Arabidopsis under normal conditions. Our results indicated that CmNAC1 is a critical factor in ABA signaling pathways and it can be utilized in transgenic breeding to improve the abiotic stress tolerance of crops. PMID:29234347

78 FR 29379 - BLM Director's Response to the Appeal by the Governors of Utah and Wyoming of the BLM Assistant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLWO320000 L13100000 DT0000 LXSIOSHL0000... Director's Governor's Consistency Review Determination AGENCY: Bureau of Land Management, Interior. ACTION... Shale and Tar Sands Resources on Lands Administered by the Bureau of Land Management (BLM) in Colorado...

Neuroprotective Effects of Reactive Oxygen Species Mediated by BDNF-Independent Activation of TrkB

PubMed Central

Huang, Yang Zhong; McNamara, James O.

2012-01-01

Reactive oxygen species (ROS) have diverse biological consequences in the mammalian CNS, but the molecular targets mediating these pleiotropic effects are incompletely understood. Like ROS, the neurotrophin receptor, TrkB receptor tyrosine kinase, has diverse effects in the developing and mature mammalian brain. Our discovery that zinc can transactivate TrkB, together with the finding that ROS can trigger zinc release from cytosolic zinc binding proteins, led us to hypothesize that ROS can transactivate TrkB in CNS neurons by a zinc-dependent mechanism. We found that both exogenous H2O2 and endogenous ROS activate TrkB signaling by a Src family kinase-dependent but brain-derived neurotrophic factor-independent mechanism in cultured rat cortical neurons. Exogenous H2O2 enhances cytosolic zinc content in a metallothionein-3 (MT-3)-requiring manner. Both exogenous H2O2 and endogenous ROS mediated transactivation of TrkB requires intracellular zinc and MT-3. The ROS-triggered transactivation of TrkB exerts neuroprotective effects, because inhibition of TrkB kinase activity or uncoupling Shc signaling from TrkB exacerbates neuronal cell death induced by H2O2. Thus, we propose a molecular signaling event whereby ROS induce release of zinc from cytosolic MT-3, the increased cytosolic zinc transactivates TrkB, and the enhanced Shc signaling downstream from TrkB promotes prosurvival effects. We suggest that such neuroprotective effects mediated by ROS are operative in diverse acute and chronic neurological disorders. PMID:23115189

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meissner, Torsten B.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215; Li, Amy

Highlights: Black-Right-Pointing-Pointer NLRC5 requires an intact NLS for its function as MHC class I transactivator. Black-Right-Pointing-Pointer Nuclear presence of NLRC5 is required for MHC class I induction. Black-Right-Pointing-Pointer Nucleotide-binding controls nuclear import and transactivation activity of NLRC5. -- Abstract: Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known,more » NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.« less

Differential regulation of p65 and c-Rel NF-kappaB transactivating activity by Cot, protein kinase C zeta and NIK protein kinases in CD3/CD28 activated T cells.

PubMed

Sánchez-Valdepeñas, Carmen; Punzón, Carmen; San-Antonio, Belén; Martin, Angel G; Fresno, Manuel

2007-03-01

It has been shown that phosphorylation of p65/RelA and c-Rel plays a role in the regulation of transcriptional activity of NF-kappaB independent on IkappaB degradation. In this study, we show that anti CD3/CD28 activation induces the transactivation activity of both p65/RelA and c-Rel in T cells using Gal4 dependent assays. Moreover, protein kinase C (PKC)zeta, Cot kinase and NF-kappaB-inducing kinase (NIK) seem to be involved in those processes in a different manner. Thus, transfection of dominant negative forms of Cot and PKCzeta inhibits CD3/CD28 induction of Gal4-p65 transactivation, whereas the kinase inactive versions of the 3 kinases inhibit induction of Gal4-c-Rel. Cot induction of Gal4-c-Rel transactivating activity seems to be mediated sequentially through PKCzeta and NIK activation, since dominant negative form of NIK blocks Cot and PKCzeta induction, whereas kinase inactive PKCzeta only blocks Cot activity. In contrast, the contribution of NIK to the transactivation function of p65/RelA seems to be negligible and more importantly NIK-KD did not inhibit induction by Cot and PKCzeta. Besides, the enhancing effect of Cot on Gal4-p65 was not decreased in mouse embryo fibroblasts from NIK deficient aly/aly mice in contrast with a greatest reduction on Gal4-c-Rel. By using Ser to Ala mutants in p65 and c-Rel transactivation domains, PKCzeta and NIK activities seem to be dependent of a restricted set of Ser in both proteins. In contrast, the enhancing effect of Cot seems to be less dependent of a particular set of Ser residues being partially abrogated by mutation of several Ser residues.

Effect of cavitation on the properties of coal-tar pitch as studied by gas-liquid chromatography

DOE Office of Scientific and Technical Information (OSTI.GOV)

M.I. Baikenov; T.B. Omarbekov; S.K. Amerkhanova

2008-02-15

The applicability of the cavitation-wave effect to coal-tar pitch processing is considered. The results of the GLC analysis of the test material before and after rotor-pulsation cavitation treatment are given. The organic matter of coal-tar pitch was found to degrade upon cavitation; as a result of this, the yields of light and medium fractions considerably increased. 5 refs., 2 figs., 4 tabs.

Comparative carcinogenic potencies of particulates from diesel engine exhausts, coke oven emissions, roofing tar aerosols and cigarette smoke.

PubMed Central

Albert, R E

1983-01-01

Mammalian cell mutagenesis, transformation and skin tumorigenesis assays show similar results in comparing the potencies of diesel, coke oven, roofing tar and cigarette smoke particulates. These assay results are reasonably consistent with the comparative carcinogenic potencies of coke oven and roofing tar emissions as determined by epidemiological studies. The bacterial mutagenesis assay tends to show disproportionately high potencies, particularly with diesel particulates. Results to date encourage the approach to the assessment for carcinogenic risks from diesel emissions based on the use of epidemiological data on cancer induced by coke oven emissions, roofing tar particulates and cigarette smoke with the comparative potencies of these materials determined by in vivo and in vitro bioassays. PMID:6186481

U.S. Army Aeromedical Research Laboratory Annual Progress Report Fiscal Year 2010

DTIC Science & Technology

2011-03-01

S. (2010). Epidermal growth factor receptor transactivation by the cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 ( TRPV1 ...induced by TRPV1 in human corneal epithelial cells. Proceedings of the Association for Research in Vision and Ophthalmology Annual Meeting, 5899/A94...presented “Novel TRPV1 -linked cell signaling pathways mediating inflammatory responses and wound healing in human corneal epithelial cells” at the Fouth

Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation.

PubMed Central

Garcia, J A; Harrich, D; Soultanakis, E; Wu, F; Mitsuyasu, R; Gaynor, R B

1989-01-01

The human immunodeficiency virus (HIV) type 1 LTR is regulated at the transcriptional level by both cellular and viral proteins. Using HeLa cell extracts, multiple regions of the HIV LTR were found to serve as binding sites for cellular proteins. An untranslated region binding protein UBP-1 has been purified and fractions containing this protein bind to both the TAR and TATA regions. To investigate the role of cellular proteins binding to both the TATA and TAR regions and their potential interaction with other HIV DNA binding proteins, oligonucleotide-directed mutagenesis of both these regions was performed followed by DNase I footprinting and transient expression assays. In the TATA region, two direct repeats TC/AAGC/AT/AGCTGC surround the TATA sequence. Mutagenesis of both of these direct repeats or of the TATA sequence interrupted binding over the TATA region on the coding strand, but only a mutation of the TATA sequence affected in vivo assays for tat-activation. In addition to TAR serving as the site of binding of cellular proteins, RNA transcribed from TAR is capable of forming a stable stem-loop structure. To determine the relative importance of DNA binding proteins as compared to secondary structure, oligonucleotide-directed mutations in the TAR region were studied. Local mutations that disrupted either the stem or loop structure were defective in gene expression. However, compensatory mutations which restored base pairing in the stem resulted in complete tat-activation. This indicated a significant role for the stem-loop structure in HIV gene expression. To determine the role of TAR binding proteins, mutations were constructed which extensively changed the primary structure of the TAR region, yet left stem base pairing, stem energy and the loop sequence intact. These mutations resulted in decreased protein binding to TAR DNA and defects in tat-activation, and revealed factor binding specifically to the loop DNA sequence. Further mutagenesis which inverted this stem and loop mutation relative to the HIV LTR mRNA start site resulted in even larger decreases in tat-activation. This suggests that multiple determinants, including protein binding, the loop sequence, and RNA or DNA secondary structure, are important in tat-activation and suggests that tat may interact with cellular proteins binding to DNA to increase HIV gene expression. Images PMID:2721501

20180312 - Retrofitting an Estrogen Receptor Transactivation Assay with Metabolic Competence Using Alginate Immobilization of Metabolic Enzymes (AIME) (SOT)

EPA Science Inventory

The VM7Luc4E2 estrogen receptor (ER) transactivation assay is an OECD approved method (TG 457) for the detection of ER agonists and antagonists, and is also part of the Tox21 high-throughput screening (HTS) portfolio. Despite its international acceptance as a screening assay, imm...

20180416 - Retrofitting an Estrogen Receptor Transactivation Assay with Metabolic Competence Using Alginate Immobilization of Metabolic Enzymes (AIME) (SETAC HTS)

EPA Science Inventory

The VM7Luc4E2 estrogen receptor (ER) transactivation assay is an OECD approved method (TG 457) for the detection of ER agonists and antagonists, and is also part of the Tox21 high-throughput screening (HTS) portfolio. Despite international acceptance as a screening assay, immorta...

Environmental research program for slagging fixed-bed coal gasification. Status report, November 1981

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilzbach, K. E.; Stetter, J. R.; Reilly, Jr., C. A.

1982-02-01

A collaborative environmental research program to provide information needed to assess the health and environmental effects associated with large-scale coal gasification technology is being conducted by Argonne National Laboratory (ANL) and the Grand Forks Energy Technology Center (GFETC). The objectives are to: investigate the toxicology and chemical composition of coal gasification by-products as a function of process variables and coal feed; compare the characteristics of isokinetic side-stream samples with those of process stream samples; identify the types of compounds responsible for toxicity; evaluate the chemical and toxicological effectiveness of various wastewater treatment operations; refine methodology for the collection and measurementmore » of organic vapors and particulates in workplace air; and obtain preliminary data on workplace air quality. So far the toxicities of a set of process stream samples (tar, oil, and gas liquor) and side-stream condensates from the GFETC gasifier have been measured in a battery of cellular screening tests for mutagenicity and cytotoxicity. Preliminary data on the effects of acute and chronic exposures of laboratory animals to process tar have been obtained. The process tar has been chemically fractionated and the distribution of mutagenicity and compound types among the fractions has been determined. Organic vapors and particulates collected at various times and locations in the gasifier building have been characterized.« less

Percentage depth dose evaluation in heterogeneous media using thermoluminescent dosimetry

PubMed Central

da Rosa, L.A.R.; Campos, L.T.; Alves, V.G.L.; Batista, D.V.S.; Facure, A.

2010-01-01

The purpose of this study is to investigate the influence of lung heterogeneity inside a soft tissue phantom on percentage depth dose (PDD). PDD curves were obtained experimentally using LiF:Mg,Ti (TLD‐100) thermoluminescent detectors and applying Eclipse treatment planning system algorithms Batho, modified Batho (M‐Batho or BMod), equivalent TAR (E‐TAR or EQTAR), and anisotropic analytical algorithm (AAA) for a 15 MV photon beam and field sizes of 1×1,2×2,5×5, and 10×10cm2. Monte Carlo simulations were performed using the DOSRZnrc user code of EGSnrc. The experimental results agree with Monte Carlo simulations for all irradiation field sizes. Comparisons with Monte Carlo calculations show that the AAA algorithm provides the best simulations of PDD curves for all field sizes investigated. However, even this algorithm cannot accurately predict PDD values in the lung for field sizes of 1×1 and 2×2cm2. An overdosage in the lung of about 40% and 20% is calculated by the AAA algorithm close to the interface soft tissue/lung for 1×1 and 2×2cm2 field sizes, respectively. It was demonstrated that differences of 100% between Monte Carlo results and the algorithms Batho, modified Batho, and equivalent TAR responses may exist inside the lung region for the 1×1cm2 field. PACS number: 87.55.kd

A case-control study of asphalt and tar exposure and lung cancer in minorities.

PubMed

McClean, Michael D; Kelsey, Karl T; Sison, Jennette D; Quesenberry, Charles P; Wrensch, Margaret R; Wiencke, John K

2011-11-01

Considerable controversy surrounds the carcinogenic potential of asphalt and tar. Since minority individuals may have had relatively high historical exposures, we investigated asphalt and tar exposure and lung cancer risk among African Americans and Latino Americans. We conducted a case-control study of lung cancer among African Americans and Latino Americans in the San Francisco Bay area (422 cases, 894 controls). A questionnaire was used to obtain detailed work histories and exposure information. Self-reported exposure to asphalt and tar as well as other factors (e.g., smoking, automobile exhaust, and asbestos) were evaluated as predictors of lung cancer risk. Potential effect modification by cytochrome P450 (CYP) 1A1 was also explored. Self-reported duration of exposure to asphalt and tar was associated with a statistically significant excess risk of lung cancer in the overall population (OR: 1.11, 95% CI: 1.01-1.22), evaluating risk per year of exposure. Years of exposure to automobile exhaust (OR: 1.02, 95% CI: 1.00-1.05) and asbestos (OR: 1.04, 95% CI: 1.02-1.06) were also associated with statistically significant elevations in risk. In Latino Americans, the lung cancer risks associated with polycyclic aromatic hydrocarbon-related exposures were consistently higher in the CYP1A1 wild-type subjects as compared to the variant genotype subjects, and the interaction was statistically significant for smoking and the CYP1A1 M2 polymorphism (P-value(interaction) = 0.02). These data are consistent with the literature suggesting that exposure to asphalt and tar may increase risk of lung cancer. However, it was not possible to separate the effects and asphalt and tar in this study. Copyright © 2011 Wiley Periodicals, Inc.

A Case-Control Study of Asphalt and Tar Exposure and Lung Cancer in Minorities

PubMed Central

McClean, Michael D.; Kelsey, Karl T.; Sison, Jennette D; Quesenberry, Charles P; Wrensch, Margaret R; Wiencke, John K.

2011-01-01

Objectives Considerable controversy surrounds the carcinogenic potential of asphalt and tar. Since minority individuals may have had relatively high historical exposures, we investigated asphalt and tar exposure and lung cancer risk among African Americans and Latino Americans. Methods We conducted a case-control study of lung cancer among African Americans and Latino Americans in the San Francisco Bay area (422 cases, 894 controls). A questionnaire was used to obtain detailed work histories and exposure information. Self-reported exposure to asphalt and tar as well as other factors (eg. smoking, automobile exhaust, and asbestos) were evaluated as predictors of lung cancer risk. Potential effect modification by cytochrome P450 (CYP) 1A1 was also explored. Results Self-reported duration of exposure to asphalt and tar was associated with a statistically significant excess risk of lung cancer in the overall population (OR: 1.11, 95%CI: 1.01–1.22), evaluating risk per year of exposure. Years of exposure to automobile exhaust (OR: 1.02, 95%CI: 1.00–1.05) and asbestos (OR: 1.04, 95%CI: 1.02–1.06) were also associated with statistically significant elevations in risk. In Latino Americans, the lung cancer risks associated with polycyclic aromatic hydrocarbon-related exposures were consistently higher in the CYP1A1 wildtype subjects as compared to the variant genotype subjects, and the interaction was statistically significant for smoking and the CYP1A1 M2 polymorphism (p-valueinteraction=0.02). Conclusions These data are consistent with the literature suggesting that exposure to asphalt and tar may increase risk of lung cancer. However, it was not possible to separate the effects and asphalt and tar in this study. PMID:21882217

Effects of thermal pretreatment and catalyst on biomass gasification efficiency and syngas composition

DOE PAGES

Cheah, Singfoong; Jablonski, Whitney S.; Olstad, Jessica L.; ...

2016-09-16

This work explores the combined effects of thermal pretreatment and using a catalyst in situ on gasification carbon conversion efficiency, as well as product gas and tar content and compositions. To compare the effects of thermal pretreatment, pelletized and ground oak with three different levels of thermal pretreatment were gasified in a fluidized bed reactor. The pretreatments applied to the oak were (1) pelletization, (2) drying at 180 °C in air, and (3) torrefaction at 270 °C in nitrogen. The oak dried at 180 °C produced syngas of similar quality and approximately the same amount of char as untreated oak.more » Torrefaction at 270 °C resulted in syngas with a higher hydrogen to CO ratio, lower methane, and less than half of the total tar -- all of which are desirable properties in terms of product gas quality. However, the oak torrefied at 270 °C also produced more than two times the amount of char as the untreated, pelletized oak. To determine the effect of catalyst, a series of experiments were conducted using olivine impregnated with nickel and cerium as the fluidized bed material in the gasifier. These tests showed that modified olivine can improve hydrogen production and reduce methane and tar levels in the syngas. The result was observed for both treated and untreated oak; although the effect was more substantial for untreated oak, for which the use of modified olivine reduced tar concentrations in the product gas by 60%, with a larger reduction in heavier tars than lighter tars. Furthermore, this result is important because reduction in heavier tar plays a more important role in benefitting downstream operations.« less

Effects of varying marijuana potency on deposition of tar and delta9-THC in the lung during smoking.

PubMed

Matthias, P; Tashkin, D P; Marques-Magallanes, J A; Wilkins, J N; Simmons, M S

1997-12-01

To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired level of intoxication ("high") reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (deltaHR) and "high" during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger MJ preparation.

Identifying the source of tar balls deposited along the beaches of Goa in 2013 and comparing with historical data collected along the West Coast of India.

PubMed

Suneel, V; Vethamony, P; Naik, B G; Krishna, M S; Jadhav, Lakshmikant

2015-09-15

Deposition of oil residues, also known as tar balls, is a seasonal phenomenon, and it occurs only in the southwest monsoon season along the west coast of India. This has become a serious environmental issue, as Goa is a global tourist destination. The present work aims at identifying the source oil of the tar balls that consistently depositing along the Goa coast using multi-marker fingerprint technique. In this context, the tar ball samples collected in May 2013 from 9 beaches of Goa coast and crude oils from different oil fields and grounded ship were subject to multi-marker analyses such as n-alkanes, pentacyclic terpanes, regular steranes, compound specific isotope analysis (CSIA) and principle component analysis (PCA). The n-alkane weathering index shows that samples have been weathered to various degrees, and the status of weathering is moderate. Since the international tanker route passes closer to the west coast of India (WCI), it is generally presumed that tanker wash is the source of the tar balls. We found that 2010/2011 tar balls are as tanker wash, but the present study demonstrates that the Bombay High (BH) oil fields can also contribute to oil contamination (tar balls) along ≈ 650 km stretch of the WCI, running from Gujarat in the north to Goa in the south. The simulated trajectories show that all the particles released in April traveled in the southeast direction, and by May, they reached the Goa coast with the influence of circulation of Indian monsoon system. Copyright © 2015 Elsevier B.V. All rights reserved.

Creating and maintaining a gas cap in tar sands formations

DOEpatents

Vinegar, Harold J.; Karanikas, John Michael; Dinkoruk, Deniz Sumnu; Wellington, Scott Lee

2010-03-16

Methods for treating a tar sands formation are disclosed herein. Methods for treating a tar sands formation may include providing heat to at least part of a hydrocarbon layer in the formation from one or more heaters located in the formation. Pressure may be allowed to increase in an upper portion of the formation to provide a gas cap in the upper portion. At least some hydrocarbons are produced from a lower portion of the formation.

Does tobacco industry marketing of 'light' cigarettes give smokers a rationale for postponing quitting?

PubMed

Gilpin, Elizabeth A; Emery, Sherry; White, Martha M; Pierce, John P

2002-01-01

The objective of this analysis was to examine further whether tobacco industry marketing using the labels light and ultra-light is perceived by smokers as a health claim. Smokers might view low tar/nicotine brands of cigarettes as a means to reduce the harm to their health from smoking and postpone quitting. Data were from smokers responding to a large, population-based survey of Californians' smoking behavior, conducted in 1996 (8,582 current smokers). Sixty percent of smokers thought the labels light and ultra-light referred to low tar/nicotine cigarettes, or otherwise implied a health claim. This percentage was higher for smokers of low tar/nicotine brands. Among smokers of regular brands, the more highly addicted, those who were trying unsuccessfully to quit, those who had cut consumption or thought about it, and those with health concerns were more likely to have considered switching. While some of these characteristics also were associated with smokers of low tar/nicotine brands, the associations were not as numerous or as strong. We conclude that some smokers appear to view low tar/nicotine brands as one short-term strategy to reduce the harm to their health from smoking without quitting. By implying reduced tar or nicotine exposure, tobacco industry marketing using the labels light and ultra-light is misleading smokers. The use of such labels should be regulated.

Lack of effect of menthol level and type on smokers' estimated mouth level exposures to tar and nicotine and perceived sensory characteristics of cigarette smoke.

PubMed

Ashley, Madeleine; Dixon, Mike; Sisodiya, Ajit; Prasad, Krishna

2012-08-01

Menthol can reduce sensory irritation and it has been hypothesised that this could result in smokers of mentholated cigarettes taking larger puffs and deeper post-puff inhalations thereby obtaining higher exposures to smoke constituents than smokers of non-mentholated cigarettes. The aim of our study was to use part-filter analysis methodology to assess the effects of cigarette menthol loading on regular and occasional smokers of mentholated cigarettes. We measured mouth level exposure to tar and nicotine and investigated the effects of mentholation on smokers' sensory perceptions such as cooling and irritation. Test cigarettes were produced containing no menthol and different loadings of synthetic and natural l-menthol at 1 and 4mg ISO tar yields. A target of 100 smokers of menthol cigarettes and 100 smokers who predominantly smoked non-menthol cigarettes from both 1 and 4mg ISO tar yield categories were recruited in Poland and Japan. Each subject was required to smoke the test cigarette types of their usual ISO tar yield. There were positive relationships between menthol loading and the perceived 'strength of menthol taste' and 'cooling' effect. However, we did not see marked menthol-induced reductions in perceived irritation or menthol-induced increases in mouth level exposure to tar and nicotine. Copyright © 2012 Elsevier Inc. All rights reserved.

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana

PubMed Central

Balfanz, Sabine

2017-01-01

The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP]i) whereas type 2 tyramine receptors can mediate Ca2+ signals or both Ca2+ signals and effects on [cAMP]i. Here; we report that the American cockroach (Periplaneta americana) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP]i. Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine. PMID:29084141

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana.

PubMed

Blenau, Wolfgang; Balfanz, Sabine; Baumann, Arnd

2017-10-30

The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP] i ) whereas type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . Here; we report that the American cockroach ( Periplaneta americana ) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP] i . Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana ; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine.

Sudan III dye strongly induces CYP1A1 mRNA expression in HepG2 cells.

PubMed

Ohno, Marumi; Ikenaka, Yoshinori; Ishizuka, Mayumi

2012-01-01

Sudan dyes possess a high affinity to the aryl hydrocarbon receptor (AHR) and potently induce its target genes, such as cytochrome P450 (CYP) 1A1, through unknown mechanisms. We investigated a detailed event occurring in cells after binding of Sudan dye to AHR in HepG2 cells. Treatment with 10 µM Sudan III caused rapid translocation of AHR into the nucleus and increased expression levels of human CYP1A1 mRNA by approximately 20-fold after 16 and 24 h. The transactivation was due to the activation of a region located at -1137 to +59 bp from CYP1A1, in particular, four xenobiotic responsive elements (XREs) existing in the region. AHR and the Ah receptor nuclear translocator interacted with XRE sequences in a gel shift assay using nuclear extract from Sudan III--treated HepG2 cells. Moreover, we suggest that constitutive androstane receptor could modify CYP1A1 transactivation by Sudan III. Copyright © 2012 Wiley Periodicals, Inc.

BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Jian; Tan Juan; Zhang Xihui

2010-05-10

Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may bemore » responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription.« less

BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription.

PubMed

Wang, Jian; Tan, Juan; Zhang, Xihui; Guo, Hongyan; Zhang, Qicheng; Guo, Tingting; Geng, Yunqi; Qiao, Wentao

2010-05-10

Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may be responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription. Copyright 2010 Elsevier Inc. All rights reserved.

Coal-tar-based pavement sealants—a potent source of PAHs

USGS Publications Warehouse

Mahler, Barbara J.; Van Metre, Peter C.

2017-01-01

P avement sealants are applied to the asphalt pavement of many parking lots, driveways, and even playgrounds in North America (Figure 1), where, when first applied, they render the pavement glossy black and looking like new. Sealant products used commercially in the central, eastern, and northern United States typically are coal-tarbased, whereas those used in the western United States typically are asphalt-based. Although the products look similar, they are chemically different. Coal-tarbased pavement sealants typically are 25-35 percent (by weight) coal tar or coal-tar pitch, materials that are known human carcinogens and that contain high concentrations of polycyclic aromatic hydrocarbons (PAHs) and related chemicals (unless otherwise noted, all Figure 1. Pavement sealant is commonly used to seal parking lots, playgrounds, and driveways throughout the United States. Sealants used in the central, northern, eastern, and southern United States typically contain coal tar or coal-tar pitch, both of which are known human carcinogens. Photos by the U.S. Geological Survey. data in this article are from Mahler et al. 2012 and references therein).

Determination of the conformational ensemble of the TAR RNA by X-ray scattering interferometry

PubMed Central

Walker, Peter

2017-01-01

Abstract The conformational ensembles of structured RNA's are crucial for biological function, but they remain difficult to elucidate experimentally. We demonstrate with HIV-1 TAR RNA that X-ray scattering interferometry (XSI) can be used to determine RNA conformational ensembles. X-ray scattering interferometry (XSI) is based on site-specifically labeling RNA with pairs of heavy atom probes, and precisely measuring the distribution of inter-probe distances that arise from a heterogeneous mixture of RNA solution structures. We show that the XSI-based model of the TAR RNA ensemble closely resembles an independent model derived from NMR-RDC data. Further, we show how the TAR RNA ensemble changes shape at different salt concentrations. Finally, we demonstrate that a single hybrid model of the TAR RNA ensemble simultaneously fits both the XSI and NMR-RDC data set and show that XSI can be combined with NMR-RDC to further improve the quality of the determined ensemble. The results suggest that XSI-RNA will be a powerful approach for characterizing the solution conformational ensembles of RNAs and RNA-protein complexes under diverse solution conditions. PMID:28108663

Coal tar-containing asphalt - resource or hazardous waste?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson-Skold, Y.; Andersson, K.; Lind, B.

2007-09-30

Coal tar was used in Sweden for the production of asphalt and for the drenching of stabilization gravel until 1973. The tar has high concentrations of polycyclic aromatic hydrocarbons (PAH), some of which may be strongly carcinogenic. Approximately 20 million tonnes of tar-containing asphalt is present in the public roads in Sweden. Used asphalt from rebuilding can be classified as hazardous waste according to the Swedish Waste Act. The cost of treating the material removed as hazardous waste can be very high due to the large amount that has to be treated, and the total environmental benefit is unclear. Themore » transport of used asphalt to landfill or combustion will affect other environmental targets. The present project, based on three case studies of road projects in Sweden, evaluates the consequences of four scenarios for handling the material: reuse, landfill, biological treatment, and incineration. The results show that reuse of the coal tar-containing materials in new road construction is the most favorable alternative in terms of cost, material use, land use, energy consumption, and air emissions.« less

Citizen science identifies the effects of nitrogen dioxide and other environmental drivers on tar spot of sycamore.

PubMed

Gosling, Laura; Ashmore, Mike; Sparks, Tim; Bell, Nigel

2016-07-01

Elevated sulphur dioxide (SO2) concentrations were the major cause of the absence of symptoms of tar spot (Rhytisma acerinum) of sycamore (Acer pseudoplatanus), in urban areas in the 1970s. The subsequent large decline in SO2 concentrations has not always been accompanied by increased tar spot symptoms, for reasons that have remained unresolved. We used a large citizen science survey, providing over 1000 records across England, to test two competing hypotheses proposed in earlier studies. We were able to demonstrate the validity of both hypotheses; tar spot symptoms were reduced where there were fewer fallen leaves as a source of inoculum, and elevated nitrogen dioxide concentrations reduced tar spot symptoms above a threshold concentration of about 20 μg m(-3). Symptom severity was also lower at sites with higher temperature and lower rainfall. Our findings demonstrate the power of citizen science to resolve competing hypotheses about the impacts of air pollution and other environmental drivers. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The birth and death of transverse aeolian ridges on Mars

USGS Publications Warehouse

Geissler, Paul E.

2014-01-01

Transverse aeolian ridges (TARs) are small bright windblown deposits found throughout the Martian tropics that stand a few meters tall and are spaced a few tens of meters apart. The origin of these features remains mysterious more than 20 years after their discovery on Mars. This paper presents a new hypothesis, that some of the TARs could be indurated dust deposits emplaced millions of years ago during periods of higher axial obliquity. It suggests that these TARs are primary depositional bed forms that accumulated in place from dust carried by the winds in suspension, perhaps in a manner comparable to antidunes on Earth, and were subsequently indurated and eroded to their current states by eons of sandblasting. It points out examples of modern dust drifts and dune-like features that appear to have been recently formed by dust accumulating directly onto the surface from atmospheric suspension. It shows how these pristine dust deposits could evolve to explain the range of morphologies of the TARs. Finally, it explains how the known properties of many TARs are consistent with this hypothesis, including their composition, thermal behavior, and distribution.

Numerical Study of Pyrolysis of Biomass in Fluidized Beds

NASA Technical Reports Server (NTRS)

Bellan, Josette; Lathouwers, Danny

2003-01-01

A report presents a numerical-simulation study of pyrolysis of biomass in fluidized-bed reactors, performed by use of the mathematical model described in Model of Fluidized Bed Containing Reacting Solids and Gases (NPO-30163), which appears elsewhere in this issue of NASA Tech Briefs. The purpose of the study was to investigate the effect of various operating conditions on the efficiency of production of condensable tar from biomass. The numerical results indicate that for a fixed particle size, the fluidizing-gas temperature is the foremost parameter that affects the tar yield. For the range of fluidizing-gas temperatures investigated, and under the assumption that the pyrolysis rate exceeds the feed rate, the optimum steady-state tar collection was found to occur at 750 K. In cases in which the assumption was not valid, the optimum temperature for tar collection was found to be only slightly higher. Scaling up of the reactor was found to exert a small negative effect on tar collection at the optimal operating temperature. It is also found that slightly better scaling is obtained by use of shallower fluidized beds with greater fluidization velocities.

An NMR (Nuclear Magnetic Resonance) Investigation of the Chemical Association and Molecular Dynamics in Asphalt Ridge Tar Sand Ore and Bitumen

DOE R&D Accomplishments Database

Netzel, D. A.; Coover, P. T.

1987-09-01

Preliminary studies on tar sand bitumen given in this report have shown that the reassociation of tar sand bitumen to its original molecular configuration after thermal stressing is a first-order process requiring nearly a week to establish equilibrium. Studies were also conducted on the dissolution of tar sand bitumen in solvents of varying polarity. At a high-weight fraction of solute to solvent the apparent molecular weight of the bitumen molecules was greater than that of the original bitumen when dissolved in chloroform-d{sub 1} and benzene-d{sub 6}. This increase in the apparent molecular weight may be due to micellar formation or a weak solute-solvent molecular complex. Upon further dilution with any of the solvents studied, the apparent molecular weight of the tar sand bitumen decreased because of reduced van der Waals forces of interaction and/or hydrogen bonding. To define the exact nature of the interactions, it will be necessary to have viscosity measurements of the solutions.

Comparison of conference abstracts and presentations with full-text articles in the health technology assessments of rapidly evolving technologies.

PubMed

Dundar, Y; Dodd, S; Dickson, R; Walley, T; Haycox, A; Williamson, P R

2006-02-01

To assess the extent of use of data from conference abstracts and presentations in health technology assessments (HTAs) provided as part of the National Institute for Health and Clinical Excellence (NICE) appraisal process. Also to assess the methodological quality of trials from conference abstracts and presentations, the consistency of reporting major outcomes between these sources and subsequent full-length publications, the effect of inclusion or exclusion of data from these sources on the meta-analysis pooled effect estimates, and the timeliness of availability of data from these sources and full articles in relation to the development of technology assessment reviews (TARs). A survey of seven TAR groups. An audit of published TARs: included all NICE TARs published between January 2000 and October 2004. Case studies of selected TARs. Analyses of the results of the survey and audit were presented as a descriptive summary and in a tabular format. Sensitivity analyses were carried out to compare the effect of inclusion of data from abstracts and presentations on the meta-analysis pooled effect estimates by including data from both abstracts/presentations and full papers, and data from only full publications, included in the original TAR. These analyses were then compared with meta-analysis of data from trials that have subsequently been published in full. All seven TAR groups completed and returned the survey. Five out of seven groups reported a general policy that included searching for and including studies available as conference abstracts/presentations. Five groups responded that if they included data from these sources they would carry out methodological quality assessment of studies from these sources using the same assessment tools as for full publications, and manage the data from these sources in the same way as fully published reports. All groups reported that if relevant outcome data were reported in both an abstract/presentation and a full publication, they would only consider the data in the full publication. Conversely, if data were only available in conference abstract/presentation, all but two groups reported that they would extract and use the data from the abstract/presentation. In total, 63 HTA reports for NICE were identified. In 20 of 63 TARs (32%) explicit statements were made with regards to inclusion and assessment of data from abstracts/presentations. Thirty-eight (60%) identified at least one randomised controlled trial (RCT) available as a conference abstract or presentation. Of these, 26 (68%) included trials available as abstracts/presentations. About 80% (20/26) of the 26 TARs that included RCTs in abstract/presentation form carried out an assessment of the methodological quality of such trials. In 16 TARs full reports of these trials were used for quality assessment where both abstracts/presentations and subsequent full publications were available. Twenty-three of 63 TARs (37%) carried out a quantitative analysis of results. Of these, ten (43%) included trials that were available as abstracts/presentations in the review; however, only 60% (6/10) of these included data from abstracts/presentations in the data analysis of results. Thirteen TARs evaluated rapidly evolving technologies and only three of these identified and included trial data from conference abstracts/presentations and carried out a quantitative analysis where abstract/presentation data were used. These three TARs were used as case studies. In all three case studies the overall quality of reporting in abstracts/presentations was generally poor. In all case studies abstracts and presentations failed to describe the method of randomisation or allocation concealment. Overall, there was no mention of blinding in 66% (25/38) of the abstracts and in 26% (7/27) of the presentations included in case studies, and one presentation (4%) explicitly stated use of intention-to-treat analysis. Results from one case study demonstrated discrepancies in data made available in abstracts or online conference presentations. Not only were discrepancies evident between these sources, but also comparison of conference abstracts/presentations with subsequently published full-length articles demonstrates data discrepancies in reporting of results. Sensitivity analyses based on one case study indicated a change in significance of effect in two outcome measures when only full papers published to date were included. There are variations in policy and practice across TAR groups regarding searching for and inclusion of studies available as conference abstracts/presentations. There is also variation in the level of detail reported in TARs regarding the use of abstracts/presentations. Therefore, TAR teams should be encouraged to state explicitly their search strategies for identifying conference abstracts and presentations, their methods for assessing these for inclusion, and where appropriate how the data were used and their effect on the results. Comprehensive searching for trials available as conference abstracts/presentations is time consuming and may be of questionable value. However, there may be a case for searching for and including abstract/presentation data if, for example, other sources of data are limited. If conference abstracts/presentations are to be included, the TAR teams need to allocate additional time for searching and managing data from these sources. Incomplete reporting in conference abstracts and presentations limits the ability of reviewers to assess confidently the methodological quality of trials. Where conference abstracts and presentations are considered for inclusion in the review, the TAR teams should increase their efforts to obtain further study details by contacting trialists. Where abstract/presentation data are included, reviewers should discuss the effect of including data from these sources. Any data discrepancies identified across sources in TARs should be highlighted and their impact discussed in the review. In addition, there is a need to carry out, for example, a sensitivity analysis with and without abstract/presentation data in the analysis. There is a need for research into the development of search strategies specific to identification of studies available as conference abstracts and presentations in TARs. Such strategies may include guidance with regard to identification of relevant electronic databases and appropriate conference sites relevant to certain clinical areas. As there are limited case studies included in this report, analyses should be repeated as more TARs accrue, or include the work of other international HTA groups.

Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide analogue rPTP.

PubMed Central

Moriyama, K; Negishi, K; Briggs, M S; Smith, C L; Hill, F; Churcher, M J; Brown, D M; Loakes, D

1998-01-01

The synthesis and enzymatic incorporation into RNA of the hydrogen bond degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA transcripts, being best incorporated in place of UTP, but also in place of CTP. When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P the transcript has similar characteristics to the wild-type TAR RNA, as demonstrated by similar melting temperatures and CD spectra. The P-substituted TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency compared with wild-type TAR. PMID:9547267

Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide analogue rPTP.

PubMed

Moriyama, K; Negishi, K; Briggs, M S; Smith, C L; Hill, F; Churcher, M J; Brown, D M; Loakes, D

1998-05-01

The synthesis and enzymatic incorporation into RNA of the hydrogen bond degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA transcripts, being best incorporated in place of UTP, but also in place of CTP. When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P the transcript has similar characteristics to the wild-type TAR RNA, as demonstrated by similar melting temperatures and CD spectra. The P-substituted TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency compared with wild-type TAR.

Surface-based 3D measurements of small aeolian bedforms on Mars and implications for estimating ExoMars rover traversability hazards

NASA Astrophysics Data System (ADS)

Balme, Matt; Robson, Ellen; Barnes, Rob; Butcher, Frances; Fawdon, Peter; Huber, Ben; Ortner, Thomas; Paar, Gerhard; Traxler, Christoph; Bridges, John; Gupta, Sanjeev; Vago, Jorge L.

2018-04-01

Recent aeolian bedforms comprising loose sand are common on the martian surface and provide a mobility hazard to Mars rovers. The ExoMars rover will launch in 2020 to one of two candidate sites: Mawrth Vallis or Oxia Planum. Both sites contain numerous aeolian bedforms with simple ripple-like morphologies. The larger examples are 'Transverse Aeolian Ridges' (TARs), which stereo imaging analyses have shown to be a few metres high and up to a few tens of metres across. Where they occur, TARs therefore present a serious, but recognized and avoidable, rover mobility hazard. There also exists a population of smaller bedforms of similar morphology, but it is unknown whether these bedforms will be traversable by the ExoMars rover. We informally refer to these bedforms as "mini-TARs", as they are about an order of magnitude smaller than most TARs observed to date. They are more abundant than TARs in the Oxia Planum site, and can be pervasive in areas. The aim of this paper is to estimate the heights of these features, which are too small to measured using High Resolution Imaging Science Experiment (HiRISE) Digital Elevation Models (DEMs), from orbital data alone. Thereby, we aim to increase our knowledge of the hazards in the proposed ExoMars landing sites. We propose a methodology to infer the height of these mini-TARs based on comparisons with similar features observed by previous Mars rovers. We use rover-based stereo imaging from the NASA Mars Exploration Rover (MER) Opportunity and PRo3D software, a 3D visualisation and analysis tool, to measure the size and height of mini-TARs in the Meridiani Planum region of Mars. These are good analogues for the smaller bedforms at the ExoMars rover candidate landing sites. We show that bedform height scales linearly with length (as measured across the bedform, perpendicular to the crest ridge) with a ratio of about 1:15. We also measured the lengths of many of the smaller aeolian bedforms in the ExoMars rover Oxia Planum candidate landing site, and find that they are similar to those of the Meridiani Planum mini-TARs. Assuming that the Oxia Planum bedforms have the same length/height ratio as the MER Opportunity mini-TARs, we combine these data to provide a probabilistic method of inferring the heights of bedforms at the Oxia Planum site. These data can then be used to explore the likely traversability of this site. For example, our method suggests that most of the bedforms studied in Oxia Planum have ridge crests higher than 15 cm, but lower than 25 cm. Hence, if the tallest bedforms the ExoMars rover will be able to safely cross are only 15 cm high, then the Oxia Planum sites studied here contain mostly impassable bedforms. However, if the rover can safely traverse 25 cm high bedforms, then most bedforms here will be smaller than this threshold. As an additional outcome, our results show that the mini-TARs have length/height ratios similar to TARs in general. Hence, these bedforms could probably be classified simply as "small TARs", rather than forming a discrete population or sub-type of aeolian bedforms.

Replication-Competent Controlled Herpes Simplex Virus

PubMed Central

Bloom, David C.; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria

2015-01-01

ABSTRACT We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. IMPORTANCE The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of multiple replication-essential genes. By directing activating heat to the region of virus administration, replication is strictly confined to infected cells within this region. The requirement for antiprogestin provides an additional level of safety, ensuring that virus replication cannot be triggered inadvertently. Replication-competent controlled vectors such as HSV-GS3 may have the potential to be superior to conventional attenuated HSV vaccine and oncolytic vectors without sacrificing safety. PMID:26269179

JPRS Report, China.

DTIC Science & Technology

1988-06-24

departments incapable of managing social economic development in Zhejiang. The broad introduction of the personal responsibility system and other... SOCIAL Wang Feng Addresses Conference on Civil Disputes, Commends Mediation Work [FAZHIBAO 14 JulJ 43 Educational Spending per High School Student Tar...RIBAO 11 JulJ 46 Zhejiang Governor Shen Zulun Calls for Personal , Administrative Efficiency fZHEJIANG RIBAO 22 JulJ 46 HONG KONG, MACAO Li Yu

Analysis of Individual Carbonaceous Particles Emitted from the Las Conchas Wildfire, Los Alamos, NM, in June-July 2011

NASA Astrophysics Data System (ADS)

Mazzoleni, C.; China, S.; Gorkowski, K.; Flowers, B. A.; Aiken, A. C.; Dubey, M. K.

2012-12-01

Carbonaceous aerosol emitted from biomass burning contributes significantly to atmospheric aerosol loadings regionally and globally. The net direct radiative forcing of biomass burning aerosol can be positive and/or negative and this depends on its composition, morphology and mixing state. Biomass burning aerosols can also change the cloud properties as they can act as cloud condensation nuclei. In this study we investigated biomass burning particles emitted from the Las Conchas wildfire in northern New Mexico that started on June 26, 2011 and burned an area of 245 square miles. Aerosol samples were collected on nucleopore filters at the Los Alamos National Laboratory during the third week of the wildfire event. Individual particles (~4000) were investigated using field-emission scanning electron microscopy and energy dispersive X-ray spectroscopy (EDS) to distinguish different carbonaceous particles and their shape, size, elemental composition and mixing state. A thermo-denuder was used to remove compounds that are volatile at temperatures up to 200 C, leaving behind the black carbon and any compounds that did not volatize completely. Smoke particles consisted of a) tar balls, which are amorphous spherical carbonaceous organic aerosols; b) organic particles with inorganic inclusions, c) soot particles and (d) soot with various inclusions. Two distinct kinds of tar balls, "electronically" dark and bright, were found using the field-emission scanning electron microscopy and were characterized for ambient and denuded conditions to understand coating effects and aging. It was found that dark tar balls are generally larger in size than the bright ones. Additionally, the difference between the size of ambient-bright and the size of denuded-bright tar balls was larger than the difference between the size of ambient-dark and the size of denuded-dark tar balls. EDS analysis showed that 70% of the dark tar balls had higher (~60%) relative oxygen content than in the bright tar balls. We conclude that there are two distinct kinds of biomass burning tar balls and that dark tar balls are less volatile than bright tar balls. The morphology of soot particles was also investigated by evaluating their fractal dimension for both ambient (coated with organic and inorganic material) and denuded samples at two different times of the day. The fractal dimension for ambient soot was found to be higher than for denuded soot due to the coating on the ambient soot particles. Finally, the monomer diameter decreased by up to 25% after denuding the particles. This study provides insights on the link between electron microscopy images of single particles and the mixing state, morphology, and evolution of different biomass burning aerosol at the beginning of their lifecycle.

Ternary Complex Factors and Cofactors Are Essential for Human T-Cell Leukemia Virus Type 1 Tax Transactivation of the Serum Response Element

PubMed Central

Shuh, Maureen; Derse, David

2000-01-01

The human T-cell leukemia virus type 1 Tax protein activates the expression of cellular immediate early genes controlled by the serum response element (SRE), which contains both the serum response factor (SRF) binding element (CArG box) and the ternary complex factor (TCF) binding element (Ets box). We show that TCF binding is necessary for Tax activation of the SRE and that Tax directly interacts with TCFs in vitro. In addition, Tax interactions with CREB binding protein (CBP) and p300- and CBP-associated factor were found to be essential for Tax activation of SRF-mediated transcription. PMID:11070040

The Effect of Substrate Contaminates on the Life of Epoxy Coatings Submerged in Sea Water

DTIC Science & Technology

1991-03-01

contaminants: coal tar, SovaPon, Mare Island and Aquapon . Aquapon is a clear (unpigmented) polyamide epoxy coating. While Aquapon is not normally used for...pigmented coatings. It was found that the Aquapon and coal tar coatings performed similarly, and blistered to the same extent, at the contamination levels...used in the test program. The Sovapon and Mare Island coatings were slightly more resistive to blistering when compared to Aquapon or coal tar but they

Aviation Turbine Fuels from Tar Sands Bitumen and Heavy Oils. Part 2. Laboratory Sample Production.

DTIC Science & Technology

1987-07-01

tar sand bitumen from West Central Kentucky; and Sunnyside tar sand bitumen from the Uinta Basin , Utah. Each of the feedstocks had unique...fuel and about 50 volume percent heavy gas oil (600-1000°F). The Westken bitumen was overall the heaviest of the four feedstocks evaluated. K factors...was 40 weight percent and about 20 weight percent in the total crude. 3. San Ardo Heavy oil The San Ardo field is located in the Coastal basin of the

48 CFR 1202.7000 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

... WORDS AND TERMS Internet Links 1202.7000 General. Most documents cited throughout (TAR) 48 CFR chapter 12, can be found on the internet. (TAR) 48 CFR chapter 12 will cite the corresponding internet...

48 CFR 1202.7000 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

... WORDS AND TERMS Internet Links 1202.7000 General. Most documents cited throughout (TAR) 48 CFR chapter 12, can be found on the internet. (TAR) 48 CFR chapter 12 will cite the corresponding internet...

48 CFR 1202.7000 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

... WORDS AND TERMS Internet Links 1202.7000 General. Most documents cited throughout (TAR) 48 CFR chapter 12, can be found on the internet. (TAR) 48 CFR chapter 12 will cite the corresponding internet...

48 CFR 1202.7000 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... WORDS AND TERMS Internet Links 1202.7000 General. Most documents cited throughout (TAR) 48 CFR chapter 12, can be found on the internet. (TAR) 48 CFR chapter 12 will cite the corresponding internet...

48 CFR 1202.7000 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... WORDS AND TERMS Internet Links 1202.7000 General. Most documents cited throughout (TAR) 48 CFR chapter 12, can be found on the internet. (TAR) 48 CFR chapter 12 will cite the corresponding internet...

Membrane curvature and the Tol-Pal complex determine polar localization of the chemoreceptor Tar in E. coli.

PubMed

Saaki, Terrens N V; Strahl, Henrik; Hamoen, Leendert W

2018-02-20

Chemoreceptors are localized at the cell poles of Escherichia coli and other rod-shaped bacteria. Over the years different mechanisms have been put forward to explain this polar localization; from stochastic clustering, membrane curvature driven localization, interactions with the Tol-Pal complex, to nucleoid exclusion. To evaluate these mechanisms, we monitored the cellular localization of the aspartate chemoreceptor Tar in different deletion mutants. We did not find any indication for either stochastic cluster formation or nucleoid exclusion. However, the presence of a functional Tol-Pal complex appeared to be essential to retain Tar at cell poles. Interestingly, Tar still accumulated at midcell in tol and in pal deletion mutants. In these mutants, the protein appears to gather at the base of division septa, a region characterised by strong membrane curvature. Chemoreceptors, like Tar, form trimer-of-dimers that bend the cell membrane due to a rigid tripod structure. The curvature approaches the curvature of the cell membrane generated during cell division, and localization of chemoreceptor tripods at curved membrane areas is therefore energetically favourable as it lowers membrane tension. Indeed, when we introduced mutations in Tar that abolish the rigid tripod structure, the protein was no longer able to accumulate at midcell or cell poles. These findings favour a model where chemoreceptor localization in E. coli is driven by strong membrane curvature and association with the Tol-Pal complex. Importance Bacteria have exquisite mechanisms to sense and to adapt to the environment they live in. One such mechanism involves the chemotaxis signal transduction pathway, in which chemoreceptors specifically bind certain attracting or repelling molecules and transduce the signals to the cell. In different rod-shaped bacteria, these chemoreceptors localize specifically to cell poles. Here, we examined the polar localization of the aspartate chemoreceptor Tar in E. coli , and found that membrane curvature at cell division sites and the Tol-Pal protein complex, localize Tar at cell division sites, the future cell poles. This study shows how membrane curvature can guide localization of proteins in a cell. Copyright © 2018 American Society for Microbiology.

Wet scrubbing of biomass producer gas tars using vegetable oil

NASA Astrophysics Data System (ADS)

Bhoi, Prakashbhai Ramabhai

The overall aims of this research study were to generate novel design data and to develop an equilibrium stage-based thermodynamic model of a vegetable oil based wet scrubbing system for the removal of model tar compounds (benzene, toluene and ethylbenzene) found in biomass producer gas. The specific objectives were to design, fabricate and evaluate a vegetable oil based wet scrubbing system and to optimize the design and operating variables; i.e., packed bed height, vegetable oil type, solvent temperature, and solvent flow rate. The experimental wet packed bed scrubbing system includes a liquid distributor specifically designed to distribute a high viscous vegetable oil uniformly and a mixing section, which was designed to generate a desired concentration of tar compounds in a simulated air stream. A method and calibration protocol of gas chromatography/mass spectroscopy was developed to quantify tar compounds. Experimental data were analyzed statistically using analysis of variance (ANOVA) procedure. Statistical analysis showed that both soybean and canola oils are potential solvents, providing comparable removal efficiency of tar compounds. The experimental height equivalent to a theoretical plate (HETP) was determined as 0.11 m for vegetable oil based scrubbing system. Packed bed height and solvent temperature had highly significant effect (p0.05) effect on the removal of model tar compounds. The packing specific constants, Ch and CP,0, for the Billet and Schultes pressure drop correlation were determined as 2.52 and 2.93, respectively. The equilibrium stage based thermodynamic model predicted the removal efficiency of model tar compounds in the range of 1-6%, 1-4% and 1-2% of experimental data for benzene, toluene and ethylbenzene, respectively, for the solvent temperature of 30° C. The NRTL-PR property model and UNIFAC for estimating binary interaction parameters are recommended for modeling absorption of tar compounds in vegetable oils. Bench scale experimental data from the wet scrubbing system would be useful in the design and operation of a pilot scale vegetable oil based system. The process model, validated using experimental data, would be a key design tool for the design and optimization of a pilot scale vegetable oil based system.

ASR5 is involved in the regulation of miRNA expression in rice.

PubMed

Neto, Lauro Bücker; Arenhart, Rafael Augusto; de Oliveira, Luiz Felipe Valter; de Lima, Júlio Cesar; Bodanese-Zanettini, Maria Helena; Margis, Rogerio; Margis-Pinheiro, Márcia

2015-11-01

The work describes an ASR knockdown transcriptomic analysis by deep sequencing of rice root seedlings and the transactivation of ASR cis-acting elements in the upstream region of a MIR gene. MicroRNAs are key regulators of gene expression that guide post-transcriptional control of plant development and responses to environmental stresses. ASR (ABA, Stress and Ripening) proteins are plant-specific transcription factors with key roles in different biological processes. In rice, ASR proteins have been suggested to participate in the regulation of stress response genes. This work describes the transcriptomic analysis by deep sequencing two libraries, comparing miRNA abundance from the roots of transgenic ASR5 knockdown rice seedlings with that of the roots of wild-type non-transformed rice seedlings. Members of 59 miRNA families were detected, and 276 mature miRNAs were identified. Our analysis detected 112 miRNAs that were differentially expressed between the two libraries. A predicted inverse correlation between miR167abc and its target gene (LOC_Os07g29820) was confirmed using RT-qPCR. Protoplast transactivation assays showed that ASR5 is able to recognize binding sites upstream of the MIR167a gene and drive its expression in vivo. Together, our data establish a comparative study of miRNAome profiles and is the first study to suggest the involvement of ASR proteins in miRNA gene regulation.

The bHLH transcription factor BIS1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in Catharanthus roseus

PubMed Central

Van Moerkercke, Alex; Steensma, Priscille; Schweizer, Fabian; Pollier, Jacob; Gariboldi, Ivo; Payne, Richard; Vanden Bossche, Robin; Miettinen, Karel; Espoz, Javiera; Purnama, Purin Candra; Kellner, Franziska; Seppänen-Laakso, Tuulikki; O’Connor, Sarah E.; Rischer, Heiko; Memelink, Johan; Goossens, Alain

2015-01-01

Plants make specialized bioactive metabolites to defend themselves against attackers. The conserved control mechanisms are based on transcriptional activation of the respective plant species-specific biosynthetic pathways by the phytohormone jasmonate. Knowledge of the transcription factors involved, particularly in terpenoid biosynthesis, remains fragmentary. By transcriptome analysis and functional screens in the medicinal plant Catharanthus roseus (Madagascar periwinkle), the unique source of the monoterpenoid indole alkaloid (MIA)-type anticancer drugs vincristine and vinblastine, we identified a jasmonate-regulated basic helix–loop–helix (bHLH) transcription factor from clade IVa inducing the monoterpenoid branch of the MIA pathway. The bHLH iridoid synthesis 1 (BIS1) transcription factor transactivated the expression of all of the genes encoding the enzymes that catalyze the sequential conversion of the ubiquitous terpenoid precursor geranyl diphosphate to the iridoid loganic acid. BIS1 acted in a complementary manner to the previously characterized ethylene response factor Octadecanoid derivative-Responsive Catharanthus APETALA2-domain 3 (ORCA3) that transactivates the expression of several genes encoding the enzymes catalyzing the conversion of loganic acid to the downstream MIAs. In contrast to ORCA3, overexpression of BIS1 was sufficient to boost production of high-value iridoids and MIAs in C. roseus suspension cell cultures. Hence, BIS1 might be a metabolic engineering tool to produce sustainably high-value MIAs in C. roseus plants or cultures. PMID:26080427

The ethylene response factor OsERF109 negatively affects ethylene biosynthesis and drought tolerance in rice.

PubMed

Yu, Yanwen; Yang, Dexin; Zhou, Shirong; Gu, Juntao; Wang, Fengru; Dong, Jingao; Huang, Rongfeng

2017-01-01

Drought is an important factor limiting plant development and crop production. Dissecting the factors involved in this process is the key for enhancement of plant tolerance to drought stress by genetic approach. Here, we evaluated the regulatory function of a novel rice ethylene response factor (ERF) OsERF109 in drought stress. Expression of OsERF109 was rapidly induced by stress and phytohormones. Subcellular localization and transactivation assay demonstrated that OsERF109 was localized in nucleus and possessed transactivation activity. Transgenic plants overexpressing (OE) and knockdown with RNA interfering (RI) OsERF109 exhibited significantly reduced and improved drought resistance, respectively, indicating that OsERF109 negatively regulates drought resistance in rice. Furthermore, measurement by gas chromatography showed that ethylene contents were less in OE while more in RI lines than these in wild types, supporting the data of drought tolerance and water loss in transgenic lines. Quantitative real-time PCR analysis also proved the regulation of OsERF109 in the expression of OSACS6, OSACO2, and OsERF3, which have been identified to play important roles in ethylene biosynthesis. Based on these results, our data evidence that OsERF109 regulates drought resistance by affecting the ethylene biosynthesis in rice. Overall, our study reveals the negative role of OsERF109 in ethylene biosynthesis and drought tolerance in rice.

Orphan nuclear receptor small heterodimer partner inhibits transforming growth factor-beta signaling by repressing SMAD3 transactivation.

PubMed

Suh, Ji Ho; Huang, Jiansheng; Park, Yun-Yong; Seong, Hyun-A; Kim, Dongwook; Shong, Minho; Ha, Hyunjung; Lee, In-Kyu; Lee, Keesook; Wang, Li; Choi, Hueng-Sik

2006-12-22

Orphan nuclear receptor small heterodimer partner (SHP) is an atypical member of the nuclear receptor superfamily; SHP regulates the nuclear receptor-mediated transcription of target genes but lacks a conventional DNA binding domain. In this study, we demonstrate that SHP represses transforming growth factor-beta (TGF-beta)-induced gene expression through a direct interaction with Smad, a transducer of TGF-beta signaling. Transient transfection studies demonstrate that SHP represses Smad3-induced transcription. In vivo and in vitro protein interaction assays revealed that SHP directly interacts with Smad2 and Smad3 but not with Smad4. Mapping of domains mediating the interaction between SHP and Smad3 showed that the entire N-terminal domain (1-159 amino acids) of SHP and the linker domain of Smad3 are involved in this interaction. In vitro glutathione S-transferase pulldown competition experiments revealed the SHP-mediated repression of Smad3 transactivation through competition with its co-activator p300. SHP also inhibits the activation of endogenous TGF-beta-responsive gene promoters, the p21, Smad7, and plasminogen activator inhibitor-1 (PAI-1) promoters. Moreover, adenovirus-mediated overexpression of SHP decreases PAI-1 mRNA levels, and down-regulation of SHP by a small interfering RNA increases both the transactivation of Smad3 and the PAI-1 mRNA levels. Finally, the PAI-1 gene is expressed in SHP(-/-) mouse hepatocytes at a higher level than in normal hepatocytes. Taken together, these data indicate that SHP is a novel co-regulator of Smad3, and this study provides new insights into regulation of TGF-beta signaling.

Ectopic activation of the rice NLR heteropair RGA4/RGA5 confers resistance to bacterial blight and bacterial leaf streak diseases.

PubMed

Hutin, Mathilde; Césari, Stella; Chalvon, Véronique; Michel, Corinne; Tran, Tuan Tu; Boch, Jens; Koebnik, Ralf; Szurek, Boris; Kroj, Thomas

2016-10-01

Bacterial blight (BB) and bacterial leaf streak (BLS) are important diseases in Oryza sativa caused by Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively. In both bacteria, transcription activator-like (TAL) effectors are major virulence determinants that act by transactivating host genes downstream of effector-binding elements (EBEs) bound in a sequence-specific manner. Resistance to Xoo is mostly related to the action of TAL effectors, either by polymorphisms that prevent the induction of susceptibility (S) genes or by executor (R) genes with EBEs embedded in their promoter, and that induce cell death and resistance. For Xoc, no resistance sources are known in rice. Here, we investigated whether the recognition of effectors by nucleotide binding and leucine-rich repeat domain immune receptors (NLRs), the most widespread resistance mechanism in plants, is also able to stop BB and BLS. In one instance, transgenic rice lines harboring the AVR1-CO39 effector gene from the rice blast fungus Magnaporthe oryzae, under the control of an inducible promoter, were challenged with transgenic Xoo and Xoc strains carrying a TAL effector designed to transactivate the inducible promoter. This induced AVR1-CO39 expression and triggered BB and BLS resistance when the corresponding Pi-CO39 resistance locus was present. In a second example, the transactivation of an auto-active NLR by Xoo-delivered designer TAL effectors resulted in BB resistance, demonstrating that NLR-triggered immune responses efficiently control Xoo. This forms the foundation for future BB and BLS disease control strategies, whereupon endogenous TAL effectors will target synthetic promoter regions of Avr or NLR executor genes. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Epstein-Barr Virus BGLF4 Kinase Downregulates NF-κB Transactivation through Phosphorylation of Coactivator UXT

PubMed Central

Chang, Ling-Shih; Wang, Jiin-Tarng; Doong, Shin-Lian; Lee, Chung-Pei; Chang, Chou-Wei; Tsai, Ching-Hwa; Yeh, Sheng-Wen; Hsieh, Ching-Yueh

2012-01-01

Epstein-Barr virus (EBV) BGLF4 is a member of the conserved herpesvirus kinases that regulate multiple cellular and viral substrates and play an important role in the viral lytic cycles. BGLF4 has been found to phosphorylate several cellular and viral transcription factors, modulate their activities, and regulate downstream events. In this study, we identify an NF-κB coactivator, UXT, as a substrate of BGLF4. BGLF4 downregulates not only NF-κB transactivation in reporter assays in response to tumor necrosis factor alpha (TNF-α) and poly(I·C) stimulation, but also NF-κB-regulated cellular gene expression. Furthermore, BGLF4 attenuates NF-κB-mediated repression of the EBV lytic transactivators, Zta and Rta. In EBV-positive NA cells, knockdown of BGLF4 during lytic progression elevates NF-κB activity and downregulates the activity of the EBV oriLyt BHLF1 promoter, which is the first promoter activated upon lytic switch. We show that BGLF4 phosphorylates UXT at the Thr3 residue. This modification interferes with the interaction between UXT and NF-κB. The data also indicate that BGLF4 reduces the interaction between UXT and NF-κB and attenuates NF-κB enhanceosome activity. Upon infection with short hairpin RNA (shRNA) lentivirus to knock down UXT, a spontaneous lytic cycle was observed in NA cells, suggesting UXT is required for maintenance of EBV latency. Overexpression of wild-type, but not phosphorylation-deficient, UXT enhances the expression of lytic proteins both in control and UXT knockdown cells. Taking the data together, transcription involving UXT may also be important for EBV lytic protein expression, whereas BGLF4-mediated phosphorylation of UXT at Thr3 plays a critical role in promoting the lytic cycle. PMID:22933289

Bovine Foamy Virus Transactivator BTas Interacts with Cellular RelB To Enhance Viral Transcription▿

PubMed Central

Wang, Jian; Tan, Juan; Guo, Hongyan; Zhang, Qicheng; Jia, Rui; Xu, Xuan; Geng, Yunqi; Qiao, Wentao

2010-01-01

Viruses are obligate intracellular parasites that depend on cellular machinery for their efficient transcription and replication. In a previous study we reported that bovine foamy virus (BFV) is able to activate the nuclear factor κB (NF-κB) pathway through the action of its transactivator BTas to enhance viral transcription. However, the mechanism used by NF-κB to enhance BFV transcription remains elusive. To address this question, we employed a yeast two-hybrid assay to screen for BTas-interacting proteins. We found that RelB, a member of NF-κB protein family, interacts with BTas. We confirmed the putative RelB-BTas interaction in vitro and in vivo and identified the protein regions responsible for the RelB-BTas interaction. Using a luciferase reporter assay, we next showed that RelB enhances BFV transcription (BTas-induced long terminal repeat [LTR] transactivation) and that this process requires both the localization of the RelB-BTas interaction in the nucleus and the Rel homology domain of RelB. The knockdown of the cellular endogenous RelB protein using small interfering RNA (siRNA) significantly attenuated BTas-induced LTR transcription. The results of chromatin immunoprecipitation (ChIP) analysis showed that endogenous RelB binds to the viral LTR in BFV-infected cells. Together, these results suggest that BFV engages the RelB protein as a cotransactivator of BTas to enhance viral transcription. In addition, our findings indicate that BFV infection upregulates cellular RelB expression through BTas-induced NF-κB activation. Thus, this study demonstrates the existence of a positive-feedback circuit in which BFV utilizes the host's NF-κB pathway through the RelB protein for efficient viral transcription. PMID:20844054

Bovine foamy virus transactivator BTas interacts with cellular RelB to enhance viral transcription.

PubMed

Wang, Jian; Tan, Juan; Guo, Hongyan; Zhang, Qicheng; Jia, Rui; Xu, Xuan; Geng, Yunqi; Qiao, Wentao

2010-11-01

Viruses are obligate intracellular parasites that depend on cellular machinery for their efficient transcription and replication. In a previous study we reported that bovine foamy virus (BFV) is able to activate the nuclear factor κB (NF-κB) pathway through the action of its transactivator BTas to enhance viral transcription. However, the mechanism used by NF-κB to enhance BFV transcription remains elusive. To address this question, we employed a yeast two-hybrid assay to screen for BTas-interacting proteins. We found that RelB, a member of NF-κB protein family, interacts with BTas. We confirmed the putative RelB-BTas interaction in vitro and in vivo and identified the protein regions responsible for the RelB-BTas interaction. Using a luciferase reporter assay, we next showed that RelB enhances BFV transcription (BTas-induced long terminal repeat [LTR] transactivation) and that this process requires both the localization of the RelB-BTas interaction in the nucleus and the Rel homology domain of RelB. The knockdown of the cellular endogenous RelB protein using small interfering RNA (siRNA) significantly attenuated BTas-induced LTR transcription. The results of chromatin immunoprecipitation (ChIP) analysis showed that endogenous RelB binds to the viral LTR in BFV-infected cells. Together, these results suggest that BFV engages the RelB protein as a cotransactivator of BTas to enhance viral transcription. In addition, our findings indicate that BFV infection upregulates cellular RelB expression through BTas-induced NF-κB activation. Thus, this study demonstrates the existence of a positive-feedback circuit in which BFV utilizes the host's NF-κB pathway through the RelB protein for efficient viral transcription.

Nuclear localization and transactivation by Vitis CBF transcription factors are regulated by combinations of conserved amino acid domains.

PubMed

Carlow, Chevonne E; Faultless, J Trent; Lee, Christine; Siddiqua, Mahbuba; Edge, Alison; Nassuth, Annette

2017-09-01

The highly conserved CBF pathway is crucial in the regulation of plant responses to low temperatures. Extensive analysis of Arabidopsis CBF proteins revealed that their functions rely on several conserved amino acid domains although the exact function of each domain is disputed. The question was what functions similar domains have in CBFs from other, overwintering woody plants such as Vitis, which likely have a more involved regulation than the model plant Arabidopsis. A total of seven CBF genes were cloned and sequenced from V. riparia and the less frost tolerant V. vinifera. The deduced species-specific amino acid sequences differ in only a few amino acids, mostly in non-conserved regions. Amino acid sequence comparison and phylogenetic analysis showed two distinct groups of Vitis CBFs. One group contains CBF1, CBF2, CBF3 and CBF8 and the other group contains CBF4, CBF5 and CBF6. Transient transactivation assays showed that all Vitis CBFs except CBF5 activate via a CRT or DRE promoter element, whereby Vitis CBF3 and 4 prefer a CRT element. The hydrophobic domains in the C-terminal end of VrCBF6 were shown to be important for how well it activates. The putative nuclear localization domain of Vitis CBF1 was shown to be sufficient for nuclear localization, in contrast to previous reports for AtCBF1, and also important for transactivation. The latter highlights the value of careful analysis of domain functions instead of reliance on computer predictions and published data for other related proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B induction

PubMed Central

Shindo, Sawako; Numazawa, Satoshi; Yoshida, Takemi

2006-01-01

CAR (constitutive androstane receptor) is a nuclear receptor that regulates the transcription of target genes, including CYP (cytochrome P450) 2B and 3A. The transactivation by CAR is regulated by its subcellular localization; however, the mechanism that governs nuclear translocation has yet to be clarified. It has been reported recently that AMPK (AMP-activated protein kinase) is involved in phenobarbital-mediated CYP2B induction in a particular culture system. We therefore investigated in vivo whether AMPK is involved in the activation of CAR-dependent gene expression. Immunoblot analysis using an antibody which recognizes Thr-172-phosphorylated AMPKα1/2 revealed phenobarbital-induced AMPK activation in rat and mouse livers as well. Phenobarbital, however, failed to increase the liver phospho-AMPK level of tumour-bearing rats in which CAR nuclear translocation had been impaired. In in vivo reporter gene assays employing PBREM (phenobarbital-responsive enhancer module) from CYP2B1, an AMPK inhibitor 8-bromo-AMP abolished phenobarbital-induced transactivation. In addition, Cyp2b10 gene expression was attenuated by 8-bromo-AMP. Forced expression of a dominant-negative mutant and the wild-type of AMPKα2 in the mouse liver suppressed and further enhanced phenobarbital-induced PBREM-reporter activity respectively. Moreover, the AMPK activator AICAR (5-amino-4-imidazolecarboxamide riboside) induced PBREM transactivation and an accumulation of CAR in the nuclear fraction of the mouse liver. However, AICAR and metformin, another AMPK activator, failed to induce hepatic CYP2B in mice and rats. These observations suggest that AMPK is at least partly involved in phenobarbital-originated signalling, but the kinase activation by itself is not sufficient for CYP2B induction in vivo. PMID:17032173

Efficient activation of transcription in yeast by the BPV1 E2 protein.

PubMed Central

Stanway, C A; Sowden, M P; Wilson, L E; Kingsman, A J; Kingsman, S M

1989-01-01

The full-length gene product encoded by the E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV1) is a transcriptional transactivator. It is believed to mediate its effect on the BPV1 long control region (LCR) by binding to motifs with the consensus sequence ACCN6GGT. The minimal functional cis active site, called the E2 response element (E2RE), in mammalian cells comprises two copies of this motif. Here we have shown that E2 can function in Saccharomyces cerevisiae by placing an E2RE upstream of a synthetic yeast assay promoter which consists of a TATA motif and an mRNA initiation site, spaced correctly. This E2RE-minimal promoter is only transcriptionally active in the presence of E2 protein and the resulting mRNA is initiated at the authentic start site. This is the first report of a mammalian viral transactivator functioning in yeast. The level of activation by E2 via the E2RE was the same as observed with the highly efficient authentic PGK promoter where the upstream activation sequence is composed of three distinct elements. Furthermore a single E2 motif which is insufficient in mammalian cells as an activation site was as efficiently utilized in yeast as the E2RE (2 motifs). Previous studies have shown that mammalian cellular activators can function in yeast and our data now extend this to viral-specific activators. Our data indicate however that while the mechanism of transactivation is broadly conserved there may be significant differences at the detailed level. Images PMID:2539584

Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters

PubMed Central

Wu, Minhao; Dong, Bin; Cao, Aiqin; Li, Hai; Liu, Jingwen

2015-01-01

Background PCSK9 has emerged as a key regulator of serum LDL-C metabolism by promoting the degradation of hepatic LDL receptor (LDLR). In this study, we investigated the effect of fasting on serum PCSK9, LDL-C, and hepatic LDLR expression in hamsters and further delineated the molecular pathways involved in fasting-induced repression of PCSK9 transcription. Results Fasting had insignificant effects on serum total cholesterol and HDL-C levels, but reduced LDL-C, triglyceride and insulin levels. The decrease in serum LDL-C was accompanied by marked reductions of hepatic PCSK9 mRNA and serum PCSK9 protein levels with concomitant increases of hepatic LDLR protein amounts. Fasting produced a profound impact on SREBP1 expression and its transactivating activity, while having modest effects on mRNA expressions of SREBP2 target genes in hamster liver. Although PPARα mRNA levels in hamster liver were elevated by fasting, ligand-induced activation of PPARα with WY14643 compound in hamster primary hepatocytes did not affect PCSK9 mRNA or protein expressions. Further investigation on HNF1α, a critical transactivator of PCSK9, revealed that fasting did not alter its mRNA expression, however, the protein abundance of HNF1α in nuclear extracts of hamster liver was markedly reduced by prolonged fasting. Conclusion Fasting lowered serum LDL-C in hamsters by increasing hepatic LDLR protein amounts via reductions of serum PCSK9 levels. Importantly, our results suggest that attenuation of SREBP1 transactivating activity owing to decreased insulin levels during fasting is primarily responsible for compromised PCSK9 gene transcription, which was further suppressed after prolonged fasting by a reduction of nuclear HNF1α protein abundance. PMID:22954675

Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.

PubMed

Oh, Eun-Taex; Park, Moon-Taek; Choi, Bo-Hwa; Ro, Seonggu; Choi, Eun-Kyung; Jeong, Seong-Yun; Park, Heon Joo

2012-04-01

Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial. Enhancement of p53 acetylation by HDAC inhibitors induces cell cycle arrest, differentiation, and apoptosis in cancer cells. The purpose of the present study was to investigate the role of p53 acetylation in the cancer cell death caused by CG200745. CG200745-induced clonogenic cell death was 2-fold greater in RKO cells expressing wild-type p53 than in p53-deficient RC10.1 cells. CG200745 treatment was also cytotoxic to PC-3 human prostate cancer cells, which express wild-type p53. CG200745 increased acetylation of p53 lysine residues K320, K373, and K382. CG200745 induced the accumulation of p53, promoted p53-dependent transactivation, and enhanced the expression of MDM2 and p21(Waf1/Cip1) proteins, which are encoded by p53 target genes. An examination of CG200745 effects on p53 acetylation using cells transfected with various p53 mutants showed that cells expressing p53 K382R mutants were significantly resistant to CG200745-induced clonogenic cell death compared with wild-type p53 cells. Moreover, p53 transactivation in response to CG200745 was suppressed in all cells carrying mutant forms of p53, especially K382R. Taken together, these results suggest that acetylation of p53 at K382 plays an important role in CG200745-induced p53 transactivation and clonogenic cell death.

Use of the bovine leukaemia virus LTR U3 promoter for expressing antisense antiviral RNAs and competitive inhibition of viral infection in cell culture.

PubMed

Shayakhmetov, D; Kovalenko, D; Yurov, G; Borisenko, A; Tikchonenko, T

1997-08-01

Use of viral inducible promoters which can be activated by virus-specific transactivator proteins to drive expression of antisense (as)RNA genes appears to be an attractive approach to inhibit virus infections in vivo. To this end, we have constructed an asRNA gene expressed from the bovine leukaemia virus (BLV) U3 promoter that is complementary to the R-U5 region of the BLV genome. This is the region that is most susceptible to inhibition by asRNA. With plasmid pLU, which expresses the asRNA gene under the control of the BLV U3 promoter, 75% inhibition of virus replication was attained in CC81 cells (the molar ratio of pLU DNA over BLV proviral DNA in the transfection mixture was 5:1). Plasmid pLT, which contains only the BLV U3 promoter without any asRNA-coding region, also efficiently (up to 60%) inhibited virus replication when cotransfected with BLV proviral DNA at a ratio of 20:1. It was suggested that competition between functional and 'empty' viral promoters for the viral transactivator protein p38tax could account for this inhibition. An immunoblotting assay showed that in the presence of nuclear extracts from CC81 cells exogenous BLV p38tax specifically associates with its responsive sequence located in the BLV U3 promoter. Moreover, the additional expression of p38tax in CC81 cells abolishes the inhibitory effect of the empty viral promoter. These observations suggest a new mechanism of BLV inhibition caused, most probably, by sequestering of the viral transactivator protein.

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

PubMed

Orr, T Edward; Whitford-Stoddard, Jennifer L; Elkins, Ralph L

2004-05-01

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.

Osmolality/salinity-responsive enhancers (OSREs) control induction of osmoprotective genes in euryhaline fish

PubMed Central

Wang, Xiaodan; Kültz, Dietmar

2017-01-01

Fish respond to salinity stress by transcriptional induction of many genes, but the mechanism of their osmotic regulation is unknown. We developed a reporter assay using cells derived from the brain of the tilapia Oreochromis mossambicus (OmB cells) to identify osmolality/salinity-responsive enhancers (OSREs) in the genes of O. mossambicus. Genomic DNA comprising the regulatory regions of two strongly salinity-induced genes, inositol monophosphatase 1 (IMPA1.1) and myo-inositol phosphate synthase (MIPS), was isolated and analyzed with dual luciferase enhancer trap reporter assays. We identified five sequences (two in IMPA1.1 and three in MIPS) that share a common consensus element (DDKGGAAWWDWWYDNRB), which we named “OSRE1.” Additional OSREs that were less effective in conferring salinity-induced trans-activation and do not match the OSRE1 consensus also were identified in both MIPS and IMPA1.1. Although OSRE1 shares homology with the mammalian osmotic-response element/tonicity-responsive enhancer (ORE/TonE) enhancer, the latter is insufficient to confer osmotic induction in fish. Like other enhancers, OSRE1 trans-activates genes independent of orientation. We conclude that OSRE1 is a cis-regulatory element (CRE) that enhances the hyperosmotic induction of osmoregulated genes in fish. Our study also shows that tailored reporter assays developed for OmB cells facilitate the identification of CREs in fish genomes. Knowledge of the OSRE1 motif allows affinity-purification of the corresponding transcription factor and computational approaches for enhancer screening of fish genomes. Moreover, our study enables targeted inactivation of OSRE1 enhancers, a method superior to gene knockout for functional characterization because it confines impairment of gene function to a specific context (salinity stress) and eliminates pitfalls of constitutive gene knockouts (embryonic lethality, developmental compensation). PMID:28289196

AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration.

PubMed

Shih, Wen-Ling; Liao, Ming-Huei; Yu, Feng-Ling; Lin, Ping-Yuan; Hsu, Hsue-Yin; Chiu, Shu-Jun

2008-11-08

We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

FIRE Data and Information

Atmospheric Science Data Center

2017-12-22

... The First ISCCP Regional Experiment is a series of field missions which have collected cirrus and marine stratocumulus ... Home Page (tar file) FIRE I - Extended Time Observations Home Page (tar file) FIRE Project Home Page for ...

Maximum yields might improve public health—if filter vents were banned: a lesson from the history of vented filters

PubMed Central

Kozlowski, L T; O'Connor, R J; Giovino, G A; Whetzel, C A; Pauly, J; Cummings, K M

2006-01-01

Filter ventilation is the dominant design feature of the modern cigarette that determines yields of tar, nicotine, and carbon monoxide on smoking machine tests. The commercial use of filter ventilation was precipitated by the 1964 United States Surgeon‐General's report, further advanced by the adoption of an official Federal Trade Commission test in 1967, and still further advanced by the inclusion of a gas phase (carbon monoxide) measure in 1979. The first vented‐filter brand on the market in the United States (Carlton) in 1964 and the second major vented‐filter brand (True) in 1966 illustrate this. Ultimately, filter ventilation became a virtually required way to make very low tar cigarettes (less than 10 mg or, even more so, less than 5 mg tar). The key to the lower tar cigarette was not, in effect, the advanced selective filtration design characteristics or sophisticated tobacco selection or processing as envisioned by experts (although these techniques were and are used); the key to the very much lower tar cigarette was simply punching holes in the filter. We propose that the banning of filter vents, coupled with low maximum standard tar, nicotine, and carbon monoxide yields, would contribute to making cigarettes much less palatable and foster smoking cessation or the use of clearly less hazardous nicotine delivery systems. It may be necessary to link low maximum yields with the banning of filter ventilation to achieve public health benefit from such maxima. PMID:16728759

Smoke composition and predicting relationships for international commercial cigarettes smoked with three machine-smoking conditions.

PubMed

Counts, M E; Morton, M J; Laffoon, S W; Cox, R H; Lipowicz, P J

2005-04-01

The study objectives were to determine the effects of smoking machine puffing parameters on mainstream smoke composition and to express those effects as predicting relationships. Forty-eight commercial Philip Morris USA and Philip Morris International cigarettes from international markets and the 1R4F reference cigarette were machine-smoked using smoking conditions defined by the International Organization of Standardization (ISO), the Massachusetts Department of Public Health (MDPH), and Health Canada (HC). Cigarette tobacco fillers were analyzed for nitrate, nicotine, tobacco-specific nitrosamines (TSNA), and ammonia. Mainstream yields for tar and 44 individual smoke constituents and "smoke pH" were determined. Cigarette constituent yields typically increased in the order ISO

TarPmiR: a new approach for microRNA target site prediction.

PubMed

Ding, Jun; Li, Xiaoman; Hu, Haiyan

2016-09-15

The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/ CONTACTS: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Characteristics of the microwave pyrolysis and microwave CO2-assisted gasification of dewatered sewage sludge.

PubMed

Chun, Young Nam; Jeong, Byeo Ri

2017-07-28

Microwave drying-pyrolysis or drying-gasification characteristics were examined to convert sewage sludge into energy and resources. The gasification was carried out with carbon dioxide as a gasifying agent. The examination results were compared with those of the conventional heating-type electric furnace to compare both product characteristics. Through the pyrolysis or gasification, gas, tar, and char were generated as products. The produced gas was the largest component of each process, followed by the sludge char and the tar. During the pyrolysis process, the main components of the produced gas were hydrogen and carbon monoxide, with a small amount of hydrocarbons such as methane and ethylene. In the gasification process, however, the amount of carbon monoxide was greater than the amount of hydrogen. In microwave gasification, a large amount of heavy tar was produced. The largest amount of benzene in light tar was generated from the pyrolysis or gasification. Ammonia and hydrogen cyanide, which are precursors of NO x , were also generated. In the microwave heating method, the sludge char produced by pyrolysis and gasification had pores in the mesopore range. This could be explained that the gas obtained from the microwave pyrolysis or gasification of the wet sewage sludge can be used as an alternative fuel, but the tar and NO x precursors in the produced gas should be treated. Sludge char can be used as a biomass solid fuel or as a tar removal adsorbent if necessary.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali Sinag; Melike Sungur; Muammer Canel

Copyrolysis of a Turkish lignite with low-density polyethylene (LDPE) is conducted in a tubular reactor. The effect of experimental conditions (temperature of 400-700{sup o}C, catalyst, LDPE contents of the mixture are 33, 50, and 67 wt %) on the formation of tar, gas, and char and their effects on the formation of phenol are investigated. The catalysts used are red mud (which is a waste product of an aluminum factory in Turkey), zeolite (Linde type A (LTA)), and K{sub 2}CO{sub 3}. Tar evolution is determined to be increased significantly by increasing the LDPE content of the coal-LDPE mixture during themore » pyrolysis. The effect of adding LDPE to the coal on the gas generation is not remarkable. An increase in temperature leads to increased gas yields. Phenol and phenol derivatives are the obstacles for the complete conversion of lignite to tar and gas. To investigate this negative effect of phenols on the yields, the phenols found in tar from coal pyrolysis are detected by gas chromatography-mass spectroscopy (GC-MS), and it is observed that phenolic structures detected in the tar obtained by individual pyrolysis of coal are dramatically decreased by adding polymer to the coal. The use of catalysts during the copyrolysis procedure leads to improved gas generation. The possible reasons of these variations are discussed. A remarkable synergetic effect between lignite and LDPE on the tar yields is also observed. 21 refs., 8 figs., 4 tabs.« less

NcoA2-Dependent Inhibition of HIF-1α Activation Is Regulated via AhR.

PubMed

Tsai, Chi-Hao; Li, Ching-Hao; Liao, Po-Lin; Cheng, Yu-Wen; Lin, Cheng-Hui; Huang, Shih-Hsuan; Kang, Jaw-Jou

2015-12-01

High endogenous levels of aryl hydrocarbon receptor (AhR) contribute to hypoxia signaling pathway inhibition following exposure to the potent AhR ligand benzo[a]pyrene (B[a]P) and could alter cellular homeostasis and disease condition. Increasing evidence indicates that AhR might compete with AhR nuclear translocator (ARNT) for complex formation with hypoxia-inducible factor-1α (HIF-1α) for transactivation, which could alter several physiological variables. Nuclear receptor coactivator 2 (NcoA2) is a transcription coactivator that regulates transcription factor activation and inhibition of basic helix-loop-helix Per (Period)-ARNT-SIM (single-minded) (bHLH-PAS) family proteins, such as HIF-1α, ARNT, and AhR, through protein-protein interactions. In this study, we demonstrated that both hypoxia and hypoxia-mimic conditions decreased NcoA2 protein expression in HEK293T cells. Hypoxia response element (HRE) and xenobiotic-responsive element (XRE) transactivation also were downregulated with NcoA2 knockdown under hypoxic conditions. In addition, B[a]P significantly decreased NcoA2 protein expression be accompanied with AhR degradation. We next evaluated whether the absence of AhR could affect NcoA2 protein function under hypoxia-mimetic conditions. NcoA2 and HIF-1α nuclear localization decreased in both B[a]P-pretreated and AhR-knockdown HepG2 cells under hypoxia-mimic conditions. Interestingly, NcoA2 overexpression downregulated HRE transactivation by competing with HIF-1α and AhR to form protein complexes with ARNT. Both NcoA2 knockdown and overexpression inhibited endothelial cell tube formation in vitro. We also demonstrated using the in vivo plug assay that NcoA2-regulated vascularization decreased in mice. Taken together, these results revealed a biphasic role of NcoA2 between AhR and hypoxic conditions, thus providing a novel mechanism underlying the cross talk between AhR and hypoxia that affects disease development and progression. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Glucocorticoids suppress tumor necrosis factor-alpha expression by human monocytic THP-1 cells by suppressing transactivation through adjacent NF-kappa B and c-Jun-activating transcription factor-2 binding sites in the promoter.

PubMed

Steer, J H; Kroeger, K M; Abraham, L J; Joyce, D A

2000-06-16

Glucocorticoid drugs suppress tumor necrosis factor-alpha (TNF-alpha) synthesis by activated monocyte/macrophages, contributing to an anti-inflammatory action in vivo. In lipopolysaccharide (LPS)-activated human monocytic THP-1 cells, glucocorticoids acted primarily on the TNF-alpha promoter to suppress a burst of transcriptional activity that occurred between 90 min and 3 h after LPS exposure. LPS increased nuclear c-Jun/ATF-2, NF-kappaB(1)/Rel-A, and Rel-A/C-Rel transcription factor complexes, which bound specifically to oligonucleotide sequences from the -106 to -88 base pair (bp) region of the promoter. The glucocorticoid, dexamethasone, suppressed nuclear binding activity of these complexes prior to and during the critical phase of TNF-alpha transcription. Site-directed mutagenesis in TNF-alpha promoter-luciferase reporter constructs showed that the adjacent c-Jun/ATF-2 (-106 to -99 bp) and NF-kappaB (-97 to -88 bp) binding sites each contributed to the LPS-stimulated expression. Mutating both sites largely prevented dexamethasone from suppressing TNF-alpha promoter-luciferase reporters. LPS exposure also increased nuclear Egr-1 and PU.1 abundance. The Egr-1/Sp1 (-172 to -161 bp) binding sites and the PU.1-binding Ets site (-116 to -110 bp) each contributed to the LPS-stimulated expression but not to glucocorticoid response. Dexamethasone suppressed the abundance of the c-Fos/c-Jun complex in THP-1 cell nuclei, but there was no direct evidence for c-Fos/c-Jun transactivation through sites in the -172 to -52 bp region. Small contributions to glucocorticoid response were attributable to promoter sequences outside the -172 to -88 bp region and to sequences in the TNF-alpha 3'-untranslated region. We conclude that glucocorticoids suppress LPS-stimulated secretion of TNF-alpha from human monocytic cells largely through antagonizing transactivation by c-Jun/ATF-2 and NF-kappaB complexes at binding sites in the -106 to -88 bp region of the TNF-alpha promoter.

Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages.

PubMed Central

Murphy, K M; Sweet, M J; Ross, I L; Hume, D A

1993-01-01

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA. Images PMID:8230418

Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells.

PubMed

Gong, J; Zhu, J; Goodman, O B; Pestell, R G; Schlegel, P N; Nanus, D M; Shen, R

2006-03-30

Androgen receptor signaling in prostate cancer cells is augmented by the androgen receptor (AR) coactivator p300, which transactivates and acetylates the AR in the presence of dihydrotestosterone (DHT). As prostate cancer (PC) cells progress to androgen independence, AR signaling remains intact, indicating that other factors stimulate AR activities in the absence of androgen. We previously reported that neuropeptide growth factors could transactivate the AR in the presence of very low concentrations of DHT. Here, we examine the involvement of p300 in neuropeptide activation of AR signaling. Transfection of increasing concentrations of p300 in the presence of bombesin into PC-3 cells resulted in a linear increase in AR transactivation, suggesting that p300 acts as a coactivator in neuropeptide-mediated AR transactivation. P300 is endowed with histone acetyltransferase (HAT) activity. Therefore, we examine the effect of bombesin on p300 HAT activity. At 4 h after the addition of bombesin, p300 HAT activity increased 2.0-fold (P<0.01). Incubation with neutral endopeptidase, which degrades bombesin, or bombesin receptor antagonists blocked bombesin-induced p300 HAT activity. To explore the potential signaling pathways involved in bombesin-induced p300 HAT activity, we examined Src and PKCdelta pathways that mediate bombesin signaling. Inhibitors of Src kinase activity or Src kinase siRNA blocked bombesin-induced p300 HAT activity, whereas PKCdelta inhibitors or PKCdelta siRNA significantly increased bombesin-induced p300 HAT activity suggesting that Src kinase and PKCdelta kinase are involved in the regulation of p300 HAT activity. As AR is acetylated in the presence of 100 nM DHT, we next examined whether bombesin-induced p300 HAT activity would result in enhanced AR acetylation. Bombesin-induced AR acetylation at the same motif KLKK observed in DHT-induced acetylation. Elimination of p300 using p300 siRNA reduced AR acetylation, demonstrating that AR acetylation was mediated by p300. AR acetylation results in AR transactivation and the expression of the AR-regulated gene prostate-specific antigen (PSA). Therefore, we examined bombesin-induced AR transactivation and PSA expression in the presence and absence of p300 siRNA and found inhibition of p300 expression reduced bombesin-induced AR transactivation and PSA expression. Together these results demonstrate that bombesin, via Src and PKCdelta signaling pathways, activates p300 HAT activity which leads to enhanced acetylation of AR resulting in increased expression of AR-regulated genes.

Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on DNA Damage-Induced Trans-Activation of p21 Gene Expression

PubMed Central

Geng, Deyu; Zhang, Zhixia; Guo, Huarong

2012-01-01

p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we report the development of a fish cell biosensor system for high throughput genotoxicity detection of new drugs, by stably integrating two reporter plasmids of pGL3-p21-luc (human p21 promoter linked to firefly luciferase) and pRL-CMV-luc (CMV promoter linked to Renilla luciferase) into marine flatfish flounder gill (FG) cells, referred to as p21FGLuc. Initial validation of this genotoxicity biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway and responded positively to the challenge of both directly acting genotoxic agents (bleomycin and mitomycin C) and indirectly acting genotoxic agents (cyclophosphamide with metabolic activation), but negatively to cyclophosphamide without metabolic activation and the non-genotoxic agents ethanol and D-mannitol, thus confirming a high specificity and sensitivity, fast and stable response to genotoxic agents for this easily maintained fish cell biosensor system. This system was especially useful in the genotoxicity detection of Di(2-ethylhexyl) phthalate (DEHP), a rodent carcinogen, but negatively reported in most non-mammalian in vitro mutation assays, by providing a strong indication of genotoxicity for DEHP. A limitation for this biosensor system was that it might give false positive results in response to sodium butyrate and any other agents, which can trans-activate the p21 gene in a p53-independent manner. PMID:25585933

EHV-1 EICP22 protein sequences that mediate its physical interaction with the immediate-early protein are not sufficient to enhance the trans-activation activity of the IE protein.

PubMed

Derbigny, Wilbert A; Kim, Seong K; Jang, Hyung K; O'Callaghan, Dennis J

2002-03-20

The early 293 amino acid EICP22 protein (EICP22P) of equine herpesvirus 1 localizes within the nucleus and functions as an accessory regulatory protein (J. Virol. 68 (1994) 4329). Transient transfection assays indicated that although the EICP22P by itself only minimally trans-activates EHV-1 promoters, the EICP22P functions synergistically with the immediate-early protein (IEP) to enhance expression of EHV-1 early genes (J. Virol. 71 (1997) 1004). We previously showed that the EICP22 protein enhances the DNA-binding activity of the EHV-1 IEP and that it also physically interacts with the IEP (J. Virol. 74 (2000) 1425). In this communication, we employed transient trans-activation assays utilizing EICP22P deletion mutants to address whether the sequences required for EICP22P-IEP physical interactions are essential for EICP22P's ability to interact synergistically with the IEP. Assays employing various classes of the EHV-1 promoters fused to the chloramphenicol acetyl-transferase (CAT) reporter gene indicated that: (1) neither full length nor any of the EICP22P mutants tested was able to overcome repression of the IE promoter elicited by the IEP, (2) the full-length EICP22P interacted synergistically with the IEP to trans-activate the early and late promoters tested, and (3) all of the EICP22P mutants, including those that were able to physically interact with IEP and itself, failed to function synergistically with the IEP to trans-activate representative EHV-1 early and late promoters. The results suggest that EICP22P sequences required for its interaction with the IE protein are not sufficient to mediate its synergistic effect on the trans-activation function of the IEP. The possible explanations as to why sequences in addition to those that mediate EICP22P-IEP interaction and EICP22P self-interactions are essential for the synergistic function of EICP22P are discussed.

Coal-Tar-Based Pavement Sealcoat and PAHs: Implications for the Environment, Human Health, and Stormwater Management

PubMed Central

2012-01-01

Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20−35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments—including stormwater runoff, lake sediment, soil, house dust, and most recently, air—contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them. PMID:22296333

Coal-tar-based pavement sealcoat and PAHs: implications for the environment, human health, and stormwater management

USGS Publications Warehouse

Mahler, Barbara J.; Van Metre, Peter C.; Crane, Judy L.; Watts, Alison W.; Scoggins, Mateo; Williams, E. Spencer

2012-01-01

Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20-35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments—including stormwater runoff, lake sediment, soil, house dust, and most recently, air—contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them.

Determination of the conformational ensemble of the TAR RNA by X-ray scattering interferometry.

PubMed

Shi, Xuesong; Walker, Peter; Harbury, Pehr B; Herschlag, Daniel

2017-05-05

The conformational ensembles of structured RNA's are crucial for biological function, but they remain difficult to elucidate experimentally. We demonstrate with HIV-1 TAR RNA that X-ray scattering interferometry (XSI) can be used to determine RNA conformational ensembles. X-ray scattering interferometry (XSI) is based on site-specifically labeling RNA with pairs of heavy atom probes, and precisely measuring the distribution of inter-probe distances that arise from a heterogeneous mixture of RNA solution structures. We show that the XSI-based model of the TAR RNA ensemble closely resembles an independent model derived from NMR-RDC data. Further, we show how the TAR RNA ensemble changes shape at different salt concentrations. Finally, we demonstrate that a single hybrid model of the TAR RNA ensemble simultaneously fits both the XSI and NMR-RDC data set and show that XSI can be combined with NMR-RDC to further improve the quality of the determined ensemble. The results suggest that XSI-RNA will be a powerful approach for characterizing the solution conformational ensembles of RNAs and RNA-protein complexes under diverse solution conditions. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A CFD model for biomass fast pyrolysis in fluidized-bed reactors

NASA Astrophysics Data System (ADS)

Xue, Qingluan; Heindel, T. J.; Fox, R. O.

2010-11-01

A numerical study is conducted to evaluate the performance and optimal operating conditions of fluidized-bed reactors for fast pyrolysis of biomass to bio-oil. A comprehensive CFD model, coupling a pyrolysis kinetic model with a detailed hydrodynamics model, is developed. A lumped kinetic model is applied to describe the pyrolysis of biomass particles. Variable particle porosity is used to account for the evolution of particle physical properties. The kinetic scheme includes primary decomposition and secondary cracking of tar. Biomass is composed of reference components: cellulose, hemicellulose, and lignin. Products are categorized into groups: gaseous, tar vapor, and solid char. The particle kinetic processes and their interaction with the reactive gas phase are modeled with a multi-fluid model derived from the kinetic theory of granular flow. The gas, sand and biomass constitute three continuum phases coupled by the interphase source terms. The model is applied to investigate the effect of operating conditions on the tar yield in a fluidized-bed reactor. The influence of various parameters on tar yield, including operating temperature and others are investigated. Predicted optimal conditions for tar yield and scale-up of the reactor are discussed.

Coal-tar-based pavement sealcoat and PAHs: implications for the environment, human health, and stormwater management.

PubMed

Mahler, Barbara J; Metre, Peter C Van; Crane, Judy L; Watts, Alison W; Scoggins, Mateo; Williams, E Spencer

2012-03-20

Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20-35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments-including stormwater runoff, lake sediment, soil, house dust, and most recently, air-contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them.

The wheat ethylene response factor transcription factor pathogen-induced ERF1 mediates host responses to both the necrotrophic pathogen Rhizoctonia cerealis and freezing stresses.

PubMed

Zhu, Xiuliang; Qi, Lin; Liu, Xin; Cai, Shibin; Xu, Huijun; Huang, Rongfeng; Li, Jiarui; Wei, Xuening; Zhang, Zengyan

2014-03-01

Sharp eyespot disease (primarily caused by the pathogen Rhizoctonia cerealis) and freezing stress are important yield limitations for the production of wheat (Triticum aestivum). Here, we report new insights into the function and underlying mechanisms of an ethylene response factor (ERF) in wheat, Pathogen-Induced ERF1 (TaPIE1), in host responses to R. cerealis and freezing stresses. TaPIE1-overexpressing transgenic wheat exhibited significantly enhanced resistance to both R. cerealis and freezing stresses, whereas TaPIE1-underexpressing wheat plants were more susceptible to both stresses relative to control plants. Following both stress treatments, electrolyte leakage and hydrogen peroxide content were significantly reduced, and both proline and soluble sugar contents were elevated in TaPIE1-overexpressing wheat, whereas these physiological traits in TaPIE1-underexpressing wheat exhibited the opposite trend. Microarray and quantitative reverse transcription-polymerase chain reaction analyses of TaPIE1-overexpressing and -underexpressing wheat plants indicated that TaPIE1 activated a subset of defense- and stress-related genes. Assays of DNA binding by electrophoretic mobility shift and transient expression in tobacco (Nicotiana tabacum) showed that the GCC boxes in the promoters of TaPIE1-activated genes were essential for transactivation by TaPIE1. The transactivation activity of TaPIE1 and the expression of TaPIE1-activated defense- and stress-related genes were significantly elevated following R. cerealis, freezing, and exogenous ethylene treatments. TaPIE1-mediated responses to R. cerealis and freezing were positively modulated by ethylene biosynthesis. These data suggest that TaPIE1 positively regulates the defense responses to R. cerealis and freezing stresses by activating defense- and stress-related genes downstream of the ethylene signaling pathway and by modulating related physiological traits in wheat.

The Wheat Ethylene Response Factor Transcription Factor PATHOGEN-INDUCED ERF1 Mediates Host Responses to Both the Necrotrophic Pathogen Rhizoctonia cerealis and Freezing Stresses1[C][W][OPEN

PubMed Central

Zhu, Xiuliang; Qi, Lin; Liu, Xin; Cai, Shibin; Xu, Huijun; Huang, Rongfeng; Li, Jiarui; Wei, Xuening; Zhang, Zengyan

2014-01-01

Sharp eyespot disease (primarily caused by the pathogen Rhizoctonia cerealis) and freezing stress are important yield limitations for the production of wheat (Triticum aestivum). Here, we report new insights into the function and underlying mechanisms of an ethylene response factor (ERF) in wheat, Pathogen-Induced ERF1 (TaPIE1), in host responses to R. cerealis and freezing stresses. TaPIE1-overexpressing transgenic wheat exhibited significantly enhanced resistance to both R. cerealis and freezing stresses, whereas TaPIE1-underexpressing wheat plants were more susceptible to both stresses relative to control plants. Following both stress treatments, electrolyte leakage and hydrogen peroxide content were significantly reduced, and both proline and soluble sugar contents were elevated in TaPIE1-overexpressing wheat, whereas these physiological traits in TaPIE1-underexpressing wheat exhibited the opposite trend. Microarray and quantitative reverse transcription-polymerase chain reaction analyses of TaPIE1-overexpressing and -underexpressing wheat plants indicated that TaPIE1 activated a subset of defense- and stress-related genes. Assays of DNA binding by electrophoretic mobility shift and transient expression in tobacco (Nicotiana tabacum) showed that the GCC boxes in the promoters of TaPIE1-activated genes were essential for transactivation by TaPIE1. The transactivation activity of TaPIE1 and the expression of TaPIE1-activated defense- and stress-related genes were significantly elevated following R. cerealis, freezing, and exogenous ethylene treatments. TaPIE1-mediated responses to R. cerealis and freezing were positively modulated by ethylene biosynthesis. These data suggest that TaPIE1 positively regulates the defense responses to R. cerealis and freezing stresses by activating defense- and stress-related genes downstream of the ethylene signaling pathway and by modulating related physiological traits in wheat. PMID:24424323

Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor.

PubMed

Thompson, P D; Hsieh, J C; Whitfield, G K; Haussler, C A; Jurutka, P W; Galligan, M A; Tillman, J B; Spindler, S R; Haussler, M R

1999-12-01

The vitamin D receptor (VDR) is a transcription factor believed to function as a heterodimer with the retinoid X receptor (RXR). However, it was reported [Schräder et al., 1994] that, on putative vitamin D response elements (VDREs) within the rat 9k and mouse 28k calcium binding protein genes (rCaBP 9k and mCaBP 28k), VDR and thyroid hormone receptor (TR) form heterodimers that transactivate in response to both 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and triiodothyronine (T(3)). We, therefore, examined associations of these receptors on the putative rCaBP 9k and mCaBP 28k VDREs, as well as on established VDREs from the rat osteocalcin (rOC) and mouse osteopontin (mOP) genes, plus the thyroid hormone response element (TRE) from the rat myosin heavy chain (rMHC) gene. In gel mobility shift assays, we found no evidence for VDR-TR heterodimer interaction with any tested element. Further, employing these hormone response elements linked to reporter genes in transfected cells, VDR and TR mediated responses to their cognate ligands only from the rOC/mOP and rMHC elements, respectively, while the CaBP elements were unresponsive to any combination of ligand(s). Utilizing the rOC and mOP VDREs, two distinct repressive actions of TR on VDR-mediated signaling were demonstrated: a T(3)-independent action, presumably via direct TR-RXR competition for DNA binding, and a T(3)-dependent repression, likely by diversion of limiting RXR from VDR-RXR toward the formation of TR-RXR heterodimers. The relative importance of these two mechanisms differed in a response element-specific manner. These results may provide a partial explanation for the observed association between hyperthyroidism and bone demineralization/osteoporosis. Copyright 1999 Wiley-Liss, Inc.

Banded TARs in Iapygia

NASA Image and Video Library

2014-09-10

The tropics of Mars are commonly littered with small bright ripples that were somehow shaped by the wind. NASA Mars Reconnaissance Orbiter might provide a valuable clue to the formation of transverse aeolian ridges TARs elsewhere on Mars.

16. GENERAL VIEW OF THE DIAMOND MINEYARD. ON THE LEFT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. GENERAL VIEW OF THE DIAMOND MINEYARD. ON THE LEFT IS THE CHIPPY HOIST HOUSE, THE MAIN HOIST HOUSE IS IN THE CENTER, AND THE SUPER HEATER, WHICH WAS USED FOR HEATING COMPRESSED AIR, IS ON THE RIGHT. THE SMALL BUILDING WAS USED FOR CLEANING ROPE CLIPS, AND FOR TOILET FACILITIES. THERE IS ALSO A TAR HOUSE, WHERE TAR WAS STORED AND KEPT WARM. ORIGINALLY EACH MINE HAD ITS OWN TAR STORAGE, BUT IT WAS EVENTUALLY CONSOLIDATED AT THE DIAMOND MINE - Butte Mineyards, Diamond Mine, Butte, Silver Bow County, MT

Selected constituents in the smokes of foreign commercial cigaretts: tar, nicotine, carbon monoxide, and carbon dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.A.; Quincy, R.B.; Guerin, M.R.

The tar, nicotine, carbon monoxide, and carbon dioxide contents of the smokes of 220 brands of foreign commercial cigarettes are reported. In some instances, filter cigarettes of certain brands were found to deliver as much or more smoke constituents than their nonfilter counterparts. Also, data indicated that there can be a great variation in the tar, nicotine, or carbon monoxide content of the smoke of samples of a given brand of cigarettes, depending on the nation in which they are purchased. 24 tables.

PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

PubMed Central

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

2013-01-01

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

PubMed

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

2013-01-04

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

EGFR transactivation is involved in TNF-α-induced expression of thymic stromal lymphopoietin in human keratinocyte cell line.

PubMed

Segawa, Ryosuke; Shigeeda, Kenichi; Hatayama, Takahiro; Dong, Jiangxu; Mizuno, Natsumi; Moriya, Takahiro; Hiratsuka, Masahiro; Hirasawa, Noriyasu

2018-03-01

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine involved in the pathology of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Tumor necrosis factor (TNF)-α, a key cytokine in inflammatory skin diseases, is a known TSLP inducer. TNF-α activates NF-κB and induces transactivation of epidermal growth factor receptor (EGFR) in epithelial cells. However, the detailed mechanism of TSLP induction by TNF-α has remained unclear. We investigated the involvement of TNF-α-induced EGFR transactivation in TSLP expression. HaCaT cells were stimulated with TNF-α or EGF in the presence or absence of an EGFR kinase inhibitor or other signaling inhibitors. The expression of TSLP mRNA was analyzed by RT-PCR and the phosphorylation level of signal proteins was analyzed by western blot. TSLP promoter and NF-κB transcription activities were analyzed by luciferase assay. TNF-α-induced TSLP expression was inhibited by the EGFR kinase inhibitor AG1478. While TSLP expression was induced by EGF, it was inhibited by the MEK inhibitor, U0126. Inhibitors of p38 and ADAM proteases suppressed the TNF-α-induced TSLP expression and EGFR phosphorylation, but not the EGF-induced expression. TNF-α-induced EGFR transactivation results in TSLP induction through ERK activation. The activation of p38 and ADAM proteases mediates TNF-α-induced EGFR phosphorylation. These findings suggested that the TNF-α-induced EGFR transactivation pathway could be a target for the treatment of inflammatory skin diseases. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells.

PubMed

Liu, G; Bibus, D M; Bode, A M; Ma, W Y; Holman, R T; Dong, Z

2001-06-19

Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (omega3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (omega6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the omega3 fatty acids EPA and DHA and of the omega6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of omega3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of omega6 to omega3 fatty acids may be a significant factor in mediating tumor development.

Injection-site vein loss and soft tissue abscesses associated with black tar heroin injection: A cross-sectional study of two distinct populations in USA.

PubMed

Summers, Phillip J; Struve, Isabelle A; Wilkes, Michael S; Rees, Vaughan W

2017-01-01

Injection-site vein loss and skin abscesses impose significant morbidity on people who inject drugs (PWID). The two common forms of street heroin available in the USA include black tar and powder heroin. Little research has investigated these different forms of heroin and their potential implications for health outcomes. A multiple-choice survey was administered to a sample of 145 participants seeking services at reduction facilities in both Sacramento, CA and greater Boston, MA, USA. Multivariate regression models for reporting one or more abscesses in one year, injection-site veins lost in six months, and soft tissue injection. Participants in Sacramento exclusively used black tar (99%), while those in Boston used powder heroin (96%). Those who used black tar heroin lost more injection-site veins (β=2.34, 95% CI: 0.66-4.03) and were more likely to report abscesses (AOR=7.68, 95% CI: 3.01-19.60). Soft tissue injection was also associated with abscesses (AOR=4.68, 95% CI: 1.84-11.93). Consistent venous access (AOR: 0.088, 95% CI: 0.011-0.74) and losing more injection sites (AOR: 1.22, 95% CI: 1.03-1.45) were associated with soft tissue injection. Use of black tar heroin is associated with more frequent abscesses and more extensive vein loss. Poor venous access predisposes people who inject drugs to soft tissue injection, which may constitute a causal pathway between black tar heroin injection and abscess formation. The mechanisms by which black tar heroin contributes to vein loss and abscess formation must be further elucidated in order to develop actionable interventions for maintaining vein health and decreasing the abscess burden. Potential interventions include increased access to clean injection equipment and education, supervised injection facilities, opioid substitution therapy, and supply chain interventions targeting cutting agents. Copyright © 2016 Elsevier B.V. All rights reserved.

[Cigarette smoking in different manners induces acute lung injury in rats].

PubMed

Xiao, Weiqiang; Zhou, Guojun; Xu, Chengyun; Xu, Jian; Huang, Fangfang; Lu, Xinbo; Li, Xia; Wu, Ximei

2016-05-25

Objective: To investigate the effects of cigarette smoking in different manners on acute lung injury in rats. Methods: The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Results: In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all P <0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all P <0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all P <0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels. Conclusion: Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.

Breast Tumorigenesis: Interaction of Two Signaling Pathways- -TGF- -beta versus Estrogen Receptor.

DTIC Science & Technology

1997-08-01

on the functional role of Smad3 and Smad4 as tumor suppressors in mediating the TGF-B signal in transactivating downstream target genes. We have...extended our analysis of the biological activity of the Smad proteins in TGF-B signaling by studying the nuclear activity of Smad2, Smad3 and Sliad4...groups using in vitro phosphorylation assays. Taken together these data suggest that Smad2 and Smad3 are inducibly phosphorylated in response to TGF-P3 and

Chemical synthesis of biologically active tat trans-activating protein of human immunodeficiency virus type 1.

PubMed Central

Chun, R; Glabe, C G; Fan, H

1990-01-01

Full-length (86-residue) polypeptide corresponding to the human immunodeficiency virus type 1 tat trans-activating protein was chemically synthesized on a semiautomated apparatus, using an Fmoc amino acid continuous-flow strategy. The bulk material was relatively homogeneous, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing, and it showed trans-activating activity when scrape loaded into cells containing a human immunodeficiency virus long terminal repeat-chloramphenicol acetyl-transferase reporter plasmid. Reverse-phase high-pressure liquid chromatography yielded a rather broad elution profile, and assays across the column for biological activity indicated a sharper peak. Thus, high-pressure liquid chromatography provided for enrichment of biological activity. Fast atom bombardment-mass spectrometry of tryptic digests of synthetic tat identified several of the predicted tryptic peptides, consistent with accurate chemical synthesis. Images PMID:2186178

Chemical characterization of the smokes of selected US commercial cigarettes: tar, nicotine, carbon monoxide, oxides of nitrogen, hydrogen cyanide, and acrolein. [32 brands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.A.; White, S.K.; Griest, W.H.

Thirty-two brands of US commercial cigarettes were analyzed for their deliveries of tar, nicotine, CO, CO/sub 2/, HCN, NO/sub x/, and acrolein under standard smoking conditions. Per cigarette and per puff deliveries were calculated. The sample suite contained filtered and non-filtered varieties, and relatively popular high, low, and medium tar delivery cigarettes. The range of deliveries of these constituents was considerable. Statistical analysis indicated that the deliveries of nicotine, CO, NO/sub x/, and HCN could usually be estimated to within 50% of their actual delivery if the tar delivery was known. However, brand to brand variation in the constituent ratiosmore » was sufficient so as to preclude the exact calculation of the delivery of one component from that of another.« less

Cigarettes, lung cancer, and coronary heart disease: the effects of inhalation and tar yield.

PubMed

Higenbottam, T; Shipley, M J; Rose, G

1982-06-01

Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for "non-inhalers", particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease.

Down in the Paleochannels

NASA Image and Video Library

2015-11-27

This whole area, located in Solis Planum, is an interesting, tectonic terrain south of Noctis Labrynthus which generally slopes toward the south as seen by NASA Mars Reconnaissance Orbiter spacecraft. Transverse aeolian ridges -- or TAR -- are mysterious, wind-blown features that are intermediate in size between ripples and much larger sand dunes. Ripples form from hopping sand grains, and dunes form from sand grains being blown over longer distances. One hypothesis for TAR formation is that larger grains like pebbles are rolled on top of smaller ripples; then, finer dust settles into the cracks, "inflating" the pebbles, making the TAR larger than typical ripples. Looking between the TAR, one sees a network of ancient, beaten-up channels that were carved by water, lava, or both. This whole area is located in Solis Planum, an interesting, tectonic terrain south of Noctis Labrynthus which generally slopes toward the south. http://photojournal.jpl.nasa.gov/catalog/PIA20157

Tobacco companies’ efforts to undermine ingredient disclosure: the Massachusetts benchmark study

PubMed Central

Velicer, Clayton; Aguinaga-Bialous, Stella; Glantz, Stanton

2015-01-01

Objectives To assess the Massachusetts Benchmark ‘Study’ (MBS) that the tobacco companies presented to the Massachusetts Department of Public Health (MDPH) in 1999 in response to ingredient disclosure regulations in the state. This case study can inform future ingredient disclosure regulations, including implementation of Articles 9 and 10 of the WHO Framework Convention on Tobacco Control (FCTC). Methods We analysed documents available at http://legacy.library.ucsf.edu to identify internal communications regarding the design and execution of the MBS and internal studies on the relationship between tar, nicotine and carbon monoxide and smoke constituents and reviewed publications that further evaluated data published as part of the MBS. Results The companies conducted extensive studies of cigarette design factors and ingredients that significantly impacted the levels of constituents. While this study asserted that by-brand emissions could be estimated reliably from published tar, nicotine, and carbon monoxide levels, the tobacco companies were well aware that factors beyond tar, nicotine and carbon monoxide influenced levels of constituents included in the study. This severely limited the potential usefulness of the MBS predictor equations. Conclusions Despite promises to provide data that would allow regulators to predict constituent data for all brands on the market, the final MBS results offered no useful predictive information to inform regulators, the scientific community or consumers. When implementing FCTC Articles 9 and 10, regulatory agencies should demand detailed by-brand information on tobacco product constituents and toxin deliveries to users. PMID:26292701

Final report on the safety assessment of Juniperus communis Extract, Juniperus oxycedrus Extract, Juniperus oxycedrus Tar, Juniperus phoenicea extract, and Juniperus virginiana Extract.

PubMed

2001-01-01

The common juniper is a tree that grows in Europe, Asia, and North America. The ripe fruit of Juniperus communis and Juniperus oxycedrus is alcohol extracted to produce Juniperus Communis Extract and Juniperus Oxycedrus Extract, respectively. Juniperus Oxycedrus Tar is the volatile oil from the wood of J. oxycedrus. Juniperus Phoenicea Extract comes from the gum of Juniperus phoenicea, and Juniperus Virginiana Extract is extracted from the wood of Juniperus virginiana. Although Juniperus Oxycedrus Tar is produced as a by-product of distillation, no information was available on the manufacturing process for any of the Extracts. Oils derived from these varieties of juniper are used solely as fragrance ingredients; they are commonly produced using steam distillation of the source material, but it is not known if that procedure is used to produce extracts. One report does state that the chemical composition of Juniper Communis Oil and Juniperus Communis Extract is similar, each containing a wide variety of terpenoids and aromatic compounds, with the occasional aliphatic alcohols and aldehydes, and, more rarely, alkanes. The principle component of Juniperus Oxycedrus Tar is cadinene, a sesquiterpene, but cresol and guaiacol are also found. No data were available, however, indicating the extent to which there would be variations in composition that may occur as a result of extraction differences or any other factor such as plant growth conditions. Information on the composition of the other ingredients was not available. All of the Extracts function as biological additives in cosmetic formulations, and Juniperus Oxycedrus Tar is used as a hair-conditioning agent and a fragrance component. Most of the available safety test data are from studies using oils derived from the various varieties of juniper. Because of the expected similarity in composition to the extract, these data were considered. Acute studies using animals show little toxicity of the oil or tar. The oils derived from J. communis and J. virginiana and Juniperus Oxycedrus Tar were not skin irritants in animals. The oil from J. virginiana was not a sensitizer, and the oil from J. communis was not phototoxic in animal tests. Juniperus Oxycedrus Tar was genotoxic in several assays. No genotoxicity data were available for any of the extracts. Juniperus Communis Extract did affect fertility and was abortifacient in studies using albino rats. Clinical tests showed no evidence of irritation or sensitization with any of the tested oils, but some evidence of sensitization to the tar. These data were not considered sufficient to assess the safety of these ingredients. Additional data needs include current concentration of use data; function in cosmetics; methods of manufacturing and impurities data, especially pesticides; ultraviolet (UV) absorption data; if absorption occurs in the UVA or UVB range, photosensitization data are needed; dermal reproductive/developmental toxicity data (to include determination of a no-effect level); two genotoxicity assays (one in a mammalian system) for each extract; if positive, a 2-year dermal carcinogenicity assay performed using National Toxicology Program (NTP) methods is needed; a 2-year dermal carcinogenicity assay performed using NTP methods on Juniperus Oxycedrus Tar; and irritation and sensitization data on each extract and the tar (these data are needed because the available data on the oils cannot be extrapolated). Until these data are available, it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.

The search for a source rock for the giant Tar Sand triangle accumulation, southeastern Utah

USGS Publications Warehouse

Huntoon, J.E.; Hansley, P.L.; Naeser, N.D.

1999-01-01

A large proportion (about 36%) of the world's oil resource is contained in accumulations of heavy oil or tar. In these large deposits of degraded oil, the oil in place represents only a fraction of what was present at the time of accumulation. In many of these deposits, the source of the oil is unknown, and the oil is thought to have migrated over long distances to the reservoirs. The Tar Sand triangle in southeastern Utah contains the largest tar sand accumulation in the United States, with 6.3 billion bbl of heavy oil estimated to be in place. The deposit is thought to have originally contained 13-16 billion bbl prior to the biodegradation, water washing, and erosion that have taken place since the middle - late Tertiary. The source of the oil is unknown. The tar is primarily contained within the Lower Permian White Rim Sandstone, but extends into permeable parts of overlying and underlying beds. Oil is interpreted to have migrated into the White Rim sometime during the Tertiary when the formation was at a depth of approximately 3500 m. This conclusion is based on integration of fluid inclusion analysis, time-temperature reconstruction, and apatite fission-track modeling for the White Rim Sandstone. Homogenization temperatures cluster around 85-90??C for primary fluid inclusions in authigenic, nonferroan dolomite in the White Rim. The fluid inclusions are associated with fluorescent oil-bearing inclusions, indicating that dolomite precipitation was coeval with oil migration. Burial reconstruction suggests that the White Rim Sandstone reached its maximum burial depth from 60 to 24 Ma, and that maximum burial was followed by unroofing from 24 to 0 Ma. Time-temperature modeling indicates that the formation experienced temperatures of 85-90??C from about 35 to 40 Ma during maximum burial. Maximum formation temperatures of about 105-110??C were reached at about 24 Ma, just prior to unroofing. Thermal modeling is used to examine the history of potential source rocks for the White Rim oil. The most attractive potential sources for White Rim oil include beds within one or more of the following formations: the Proterozoic Chuar Group, which is present in the subsurface southwest of the Tar Sand triangle; the Mississippian Delle Phosphatic Member of the Deseret Limestone and equivalent formations, the Permian Kaibab Limestone, the Sinbad Limestone Member of the Triassic Moenkopi Formation, and the Jurassic Arapien Shale, Twin Creek Limestone, and Carmel Formation, which are present west of the Tar Sand triangle; the Pennsylvanian Paradox Formation in the Paradox basin east of the Tar Sand triangle; and the Permian Park City Formation northwest of the Tar Sand triangle. Each formation has a high total organic carbon content and is distributed over a wide enough geographic area to have provided a huge volume of oil. Source beds in all of the formations reached thermal maturity at times prior to or during the time that migration into the White Rim is interpreted to have occurred. Based on all available data, the most likely source for the Tar Sand triangle appears to be the Mississippian Delle Phosphatic Member of the Deseret Limestone. Secondary migration out of the Delle is interpreted to have occurred during the Cretaceous, during Sevier thrusting. Subsequent tertiary migration into the Tar Sand triangle reservoir is interpreted to have occurred later, during middle Tertiary Laramide deformation.

C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8.

PubMed Central

Dörfler, P; Busslinger, M

1996-01-01

Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning. In this study we have analysed the structural requirements for transcriptional activation by BSAP. In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine/threonine/proline-rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions. This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH. The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus. The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain. The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8, the zebrafish Pax-b as well as the sea urchin Pax-258 proteins. These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences. Images PMID:8617244

An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain.

PubMed

Reynaud, Rachel; Barlier, Anne; Vallette-Kasic, Sophie; Saveanu, Alexandru; Guillet, Marie-Pierre; Simonin, Gilbert; Enjalbert, Alain; Valensi, Paul; Brue, Thierry

2005-08-01

PROP1 gene mutations are usually associated with childhood onset GH and TSH deficiencies, whereas gonadotroph deficiency is diagnosed at pubertal age. We report a novel PROP1 mutation revealed by familial normosmic hypogonadotropic hypogonadism. We performed in vitro transactivation and DNA binding experiments to study functional consequences of this mutation. Three brothers were followed in the Department of Endocrinology of a French university hospital. These patients from a consanguineous kindred were referred for cryptorchidism and/or delayed puberty. Initial investigations revealed hypogonadotropic hypogonadism. One of the patients had psychomotor retardation, intracranial hypertension, and minor renal malformations. The brothers reached normal adult height and developed GH and TSH deficiencies after age 30. A novel homozygous nonsense mutation (W194X) was found in the PROP1 gene, indicating that the protein is truncated in its transactivation domain. Transfection studies confirmed the deleterious effect of this mutation, whose transactivation capacity was only 34.4% of that of the wild-type. Unexpectedly altered DNA-binding properties suggested that the C-terminal end of the factor plays a role in protein-DNA interaction. PROP1 mutations should be considered among the growing number of genetic causes of initially isolated hypogonadotropic hypogonadism. This report extends the phenotype variability associated with PROP1 mutations.

Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fayerweather, W.E.

2007-07-01

The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimatedmore » by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.« less

Physicochemical Approaches for the Remediation of Former Manufactured Gas Plant Tars

NASA Astrophysics Data System (ADS)

Hauswirth, S.; Miller, C. T.

2014-12-01

Former manufactured gas plant (FMGP) tars are one of the most challenging non-aqueous phase liquid (NAPL) contaminants to remediate due to their complex chemical composition, high viscosities, and ability to alter wettability. In this work, we investigate several in situ remediation techniques for the removal of tar from porous media. Batch and column experiments were conducted to test the effectiveness of mobilization, solubilization, and chemical oxidation remediation approaches. Alkaline (NaOH), surfactant (Triton X-100), and polymer (xanthan gum) agents were used in various combinations to reduce tar-water interfacial tension, increase flushing solution viscosity, and increase the solubilities of tar components. Base-activated sodium persulfate was used alone and in combination with surfactant to chemically oxidized tar components. The effectiveness of each method was assessed in terms of both removal of PAHs from the system and reduction of dissolved-phase effluent polycyclic aromatic hydrocarbon (PAH) concentrations. In column studies, alkaline-polymer (AP) and alkaline-surfactant-polymer (ASP) solutions efficiently mobilized 81-93% and 95-96% of residual PAHs, respectively, within two pore volumes. The impact of AP flushing on dissolved-phase PAH concentrations was relatively low; however, the concentrations of several low molar mass PAHs were significantly reduced after ASP flushing. Surfactant-polymer (SP) solutions removed over 99% of residual PAHs through a combination of mobilization and solubilization, and reduced the post-remediation, dissolved-phase total PAH concentration by 98.4-99.1%. Degradation of residual PAHs by base-activated sodium persulfate was relatively low (30-50%), and had little impact on dissolved-phase PAH concentrations.

Social-cognitive remediation in schizophrenia: generalization of effects of the Training of Affect Recognition (TAR).

PubMed

Wölwer, Wolfgang; Frommann, Nicole

2011-09-01

In the last decade, several social cognitive remediation programs have been developed for use in schizophrenia. Though existing evidence indicates that such programs can improve social cognition, which is essential for successful social functioning, it remains unclear whether the improvements generalize to social cognitive domains not primarily addressed by the intervention and whether the improved test performance transfers into everyday social functioning. The present study investigated whether, beyond its known effects on facial affect recognition, the Training of Affect Recognition (TAR) has effects on prosodic affect recognition, theory of mind (ToM) performance, social competence in a role-play task, and more general social and occupational functioning. Thirty-eight inpatients with a diagnosis of schizophrenia or schizoaffective disorder were randomly assigned to 6 weeks of treatment with the TAR--primarily targeted at facial affect recognition-or Cognitive Remediation Training (CRT)--primarily targeted at neurocognition. Intention-to-treat analyses found significantly larger pre-post improvements with TAR than with CRT in prosodic affect recognition, ToM, and social competence and a trend effect in global social functioning. However, the effects on ToM and social competence were no longer significant in the smaller group of patients who completed treatment according to protocol. Results suggest that TAR effects generalize to other social cognitive domains not primarily addressed. TAR may also enhance social skills and social functioning, although this has to be confirmed. Results are discussed with regard to the need to improve functional outcome in schizophrenia against the background of current evidence from other social cognitive remediation approaches.

48 CFR 1237.7002 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF CONTRACTING SERVICE CONTRACTING Department of Transportation Procedures for Acquiring Training Services 1237.7002 Applicability. The policy at (TAR) 48 CFR 1237.7000 applies to all contracts (as defined... control the course content or presentation. (See (TAR) 48 CFR 1213.7100 for examples.) ...

46 CFR Table II to Part 150 - Grouping of Cargoes

Code of Federal Regulations, 2010 CFR

2010-10-01

... solutions Clay slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid, Diethanolamine salt... Coal tar, high temperature Coal tar pitch Decahydronaphthalene Degummed C9 (DOW) Diphenyl, Diphenyl... Gas, high pour Heartcut distillate Linseed Lubricating Mineral Mineral seal Motor Neatsfoot...

46 CFR Table II to Part 150 - Grouping of Cargoes

Code of Federal Regulations, 2011 CFR

2011-10-01

... solutions Clay slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid, Diethanolamine salt... Coal tar, high temperature Coal tar pitch Decahydronaphthalene Degummed C9 (DOW) Diphenyl, Diphenyl... Gas, high pour Heartcut distillate Linseed Lubricating Mineral Mineral seal Motor Neatsfoot...

46 CFR Table II to Part 150 - Grouping of Cargoes

Code of Federal Regulations, 2012 CFR

2012-10-01

... solutions Clay slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid, Diethanolamine salt... Coal tar, high temperature Coal tar pitch Decahydronaphthalene Degummed C9 (DOW) Diphenyl, Diphenyl... Gas, high pour Heartcut distillate Linseed Lubricating Mineral Mineral seal Motor Neatsfoot...

SULFUR TOLERANT CATALYSTS FOR BIOMASS TAR REMOVAL - PHASE I

EPA Science Inventory

In this Small Business Innovation Research (SBIR) project, NexTech Materials proposes a catalytic reforming approach to remove waste tar from gasified biomass on nickel-based catalysts. Biomass gasification is a potential renewable route to producing electricity, liquid fue...

Yields of tar, nicotine, and carbon monoxide in the sidestream smoke from 15 brands of Canadian cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rickert, W.S.; Robinson, J.C.; Collishaw, N.

Sidestream smoke yields for 15 brands of cigarettes were determined under conditions where mainstream yields were approximately equal to those used for determining the values which appear on packages of Canadian cigarettes. Sidestream yields of tar, nicotine, and carbon monoxide were much higher than mainstream yields for all brands tested. The average sidestream-to-mainstream ratios for the 15 brands were 3.5, 6.6, and 6.8 for tar, nicotine, and carbon monoxide, respectively. The highest yields of sidestream were obtained from the brands with the lowest mainstream yields.

Creating fluid injectivity in tar sands formations

DOEpatents

Stegemeier, George Leo; Beer, Gary Lee; Zhang, Etuan

2012-06-05

Methods for treating a tar sands formation are described herein. Methods for treating a tar sands may include heating a portion of a hydrocarbon layer in the formation from one or more heaters located in the portion. The heat may be controlled to increase the permeability of at least part of the portion to create an injection zone in the portion with an average permeability sufficient to allow injection of a fluid through the injection zone. A drive fluid and/or an oxidizing fluid may be provided into the injection zone. At least some hydrocarbons including mobilized hydrocarbons are produced from the portion.

Creating fluid injectivity in tar sands formations

DOEpatents

Stegemeier, George Leo; Beer, Gary Lee; Zhang, Etuan

2010-06-08

Methods for treating a tar sands formation are described herein. Methods for treating a tar sands may include heating a portion of a hydrocarbon layer in the formation from one or more heaters located in the portion. The heat may be controlled to increase the permeability of at least part of the portion to create an injection zone in the portion with an average permeability sufficient to allow injection of a fluid through the injection zone. A drive fluid and/or an oxidizing fluid may be provided into the injection zone. At least some hydrocarbons are produced from the portion.

In situ heat treatment of a tar sands formation after drive process treatment

DOEpatents

Vinegar, Harold J.; Stanecki, John

2010-09-21

A method for treating a tar sands formation includes providing a drive fluid to a hydrocarbon containing layer of the tar sands formation to mobilize at least some hydrocarbons in the layer. At least some first hydrocarbons from the layer are produced. Heat is provided to the layer from one or more heaters located in the formation. At least some second hydrocarbons are produced from the layer of the formation. The second hydrocarbons include at least some hydrocarbons that are upgraded compared to the first hydrocarbons produced by using the drive fluid.

Tar analysis from biomass gasification by means of online fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Baumhakl, Christoph; Karellas, Sotirios

2011-07-01

Optical methods in gas analysis are very valuable mainly due to their non-intrusive character. That gives the possibility to use them for in-situ or online measurements with only optical intervention in the measurement volume. In processes like the gasification of biomass, it is of high importance to monitor the gas quality in order to use the product gas in proper machines for energy production following the restrictions in the gas composition but also improving its quality, which leads to high efficient systems. One of the main problems in the biomass gasification process is the formation of tars. These higher hydrocarbons can lead to problems in the operation of the energy system. Up to date, the state of the art method used widely for the determination of tars is a standardized offline measurement system, the so-called "Tar Protocol". The aim of this work is to describe an innovative, online, optical method for determining the tar content of the product gas by means of fluorescence spectroscopy. This method uses optical sources and detectors that can be found in the market at low cost and therefore it is very attractive, especially for industrial applications where cost efficiency followed by medium to high precision are of high importance.

Characteristics of PAH tar oil contaminated soils-Black particles, resins and implications for treatment strategies.

PubMed

Trellu, Clément; Miltner, Anja; Gallo, Rosita; Huguenot, David; van Hullebusch, Eric D; Esposito, Giovanni; Oturan, Mehmet A; Kästner, Matthias

2017-04-05

Tar oil contamination is a major environmental concern due to health impacts of polycyclic aromatic hydrocarbons (PAH) and the difficulty of reaching acceptable remediation end-points. Six tar oil-contaminated soils with different industrial histories were compared to investigate contamination characteristics by black particles. Here we provide a simple method tested on 6 soils to visualize and identify large amounts of black particles (BP) as either solid aggregates of resinified and weathered tar oil or various wood/coke/coal-like materials derived from the contamination history. These materials contain 2-10 times higher PAH concentrations than the average soil and were dominantly found in the sand fraction containing 42-86% of the total PAH. The PAH contamination in the different granulometric fractions was directly proportional to the respective total organic carbon content, since the PAH were associated to the carbonaceous particulate materials. Significantly lower (bio)availability of PAH associated to these carbonaceous phases is widely recognized, thus limiting the efficiency of remediation techniques. We provide a conceptual model of the limited mass transfer of PAH from resinated tar oil phases to the water phase and emphasize the options to physically separate BP based on their lower bulk density and slower settling velocity. Copyright © 2017 Elsevier B.V. All rights reserved.

DeepMirTar: a deep-learning approach for predicting human miRNA targets.

PubMed

Wen, Ming; Cong, Peisheng; Zhang, Zhimin; Lu, Hongmei; Li, Tonghua

2018-06-01

MicroRNAs (miRNAs) are small noncoding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression by targeting messenger RNAs (mRNAs). Because the underlying mechanisms associated with miRNA binding to mRNA are not fully understood, a major challenge of miRNA studies involves the identification of miRNA-target sites on mRNA. In silico prediction of miRNA-target sites can expedite costly and time-consuming experimental work by providing the most promising miRNA-target-site candidates. In this study, we reported the design and implementation of DeepMirTar, a deep-learning-based approach for accurately predicting human miRNA targets at the site level. The predicted miRNA-target sites are those having canonical or non-canonical seed, and features, including high-level expert-designed, low-level expert-designed, and raw-data-level, were used to represent the miRNA-target site. Comparison with other state-of-the-art machine-learning methods and existing miRNA-target-prediction tools indicated that DeepMirTar improved overall predictive performance. DeepMirTar is freely available at https://github.com/Bjoux2/DeepMirTar_SdA. lith@tongji.edu.cn, hongmeilu@csu.edu.cn. Supplementary data are available at Bioinformatics online.

Performance of Ni/dolomite pellet catalyst on gas distribution from cassava rhizome gasification with a modular fixed-bed gasifier.

PubMed

Sricharoenchaikul, V; Atong, D; Sornkade, P; Nisamaneenate, J

2017-05-01

Thermal conversion of cassava rhizome was performed using a modular downdraft gasifier with the addition of Ni-based catalysts as promising tar eliminating and produced gas upgrading techniques. The activities of a synthesized 5% Ni/dolomite pellet catalyst prepared by impregnation method were investigated in a secondary reactor downstream of the gasifier. High reforming activity of the Ni/dolomite pellet catalyst on tar reduction was achieved. The conversion to H 2 and CO was improved via steam reforming of methane and char reaction with CO 2 . Moreover, the formation of CH 4 and C x H y was diminished through the tar or condensable hydrocarbon reformed on the catalyst surface. The carbon and hydrogen conversions of cassava rhizome with prepared catalyst were 83.79% and 61.78%, respectively, at an air flow rate of 1.98 m 3 /hr. At this condition, tar formation was low, while the lower heating value was 4.39 MJ/m 3 and H 2 to CO molar ratio was 1.22. Generally, the addition of a catalyst not only enhanced gas production, but also reduced tar and particulate matter generation; thus, its implementation should help lessen the pollution control requirement and cost of operation, while allowing higher quality fuel gas production.

Localization of HTLV-I tax proviral DNA in mononuclear cells.

PubMed

Zucker-Franklin, Dorothea; Pancake, Bette A; Najfeld, Vesna

2003-01-01

The tax sequence of HTLV-I is demonstrable in the skin and blood mononuclear cells of patients with mycosis fungoides, as well as in the mononuclear leukocytes of some healthy blood donors, but was not demonstrable when PCR/Southern analyses were carried out on preparations of high-molecular-weight genomic DNA. Therefore, it was postulated that tax DNA may not be integrated. To investigate this possibility fluorescence in situ hybridization was carried out on cells arrested in metaphase, using a probe containing the HTLV-I tax proviral DNA full-length open reading frame coding sequence. While metaphases prepared from C91PL cells, a cell line infected with HTLV-I, showed an abundance of chromosome-associated as well as extra-chromosomal signals, metaphases prepared with blood mononuclear cells from healthy tax sequence positive donors did not reveal any tax DNA associated with chromosomes. Such signals were readily detected extra-chromosomally. Although it has been demonstrated that transactivation of genes by gene products encoded by extra-chromosomal DNA may have nosocomial implications, whether transactivation by p40 tax generated from extra-chromosomal tax sequences is responsible for the development of neoplasia remains to be investigated.

PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator

PubMed Central

Regad, Tarik; Saib, Ali; Lallemand-Breitenbach, Valérie; Pandolfi, Pier Paolo; de Thé, Hugues; Chelbi-Alix, Mounira K.

2001-01-01

The promyelocytic leukaemia (PML) protein localizes in the nucleus both in the nucleoplasm and in matrix-associated multiprotein complexes known as nuclear bodies (NBs). The number and the intensity of PML NBs increase in response to interferon (IFN). Overexpression of PML affects the replication of vesicular stomatitis virus and influenza virus. However, PML has a less powerful antiviral activity against these viruses than the IFN mediator MxA. Here, we show that overexpression of PML, but not that of Mx1 or MxA, leads to a drastic decrease of a complex retrovirus, the human foamy virus (HFV), gene expression. PML represses HFV transcription by complexing the HFV transactivator, Tas, preventing its direct binding to viral DNA. This physical interaction requires the N-terminal region of Tas and the RING finger of PML, but does not necessitate PML localization in NBs. Finally, we show that IFN treatment inhibits HFV replication in wild-type but not in PML–/– cells. These findings point to a role for PML in transcriptional repression and suggest that PML could play a key role in mediating an IFN-induced antiviral state against a complex retrovirus. PMID:11432836

A role for NF-κB–dependent gene transactivation in sunburn

PubMed Central

Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

2000-01-01

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

Whole-genome analysis of genetic recombination of hepatitis delta virus: molecular domain in delta antigen determining trans-activating efficiency.

PubMed

Chao, Mei; Lin, Chia-Chi; Lin, Feng-Ming; Li, Hsin-Pai; Iang, Shan-Bei

2015-12-01

Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.

Tabulations of Responses from the 2000 Survey of Reserve Component Personnel: Volume 3. Benefits and Programs

DTIC Science & Technology

2002-08-01

10 months to 12 months 7 months to less than 10 months 5 months to...Administrative data were used to resolve conflicts between answers, to fill in missing survey data, and to determine if an AGR/TAR/AR was Title 10 or Title 32... 7 2a.2 Length of Time Served in Active Army (USA): By Paygrade and Gender

EPI-001, a compound active against castration-resistant prostate cancer, targets transactivation unit 5 of the androgen receptor

PubMed Central

De Mol, Eva; Fenwick, R. Bryn; Phang, Christopher T. W.; Buzón, Victor; Szulc, Elzbieta; de la Fuente, Alex; Escobedo, Albert; García, Jesús; Bertoncini, Carlos W.; Estébanez-Perpiñá, Eva; McEwan, Iain J.; Riera, Antoni; Salvatella, Xavier

2016-01-01

Castration-resistant prostate cancer is the lethal condition suffered by prostate cancer patients that become refractory to androgen deprivation therapy. EPI-001 is a recently identified compound active against this condition that modulates the activity of the androgen receptor, a nuclear receptor that is essential for disease progression. The mechanism by which this compound exerts its inhibitory activity is however not yet fully understood. Here we show, by using high resolution solution nuclear magnetic resonance spectroscopy, that EPI-001 selectively interacts with a partially folded region of the transactivation domain of the androgen receptor, known as transactivation unit 5, that is key for the ability of prostate cells to proliferate in the absence of androgens, a distinctive feature of castration-resistant prostate cancer. Our results can contribute to the development of more potent and less toxic novel androgen receptor antagonists for treating this disease. PMID:27356095

The 9aaTAD Transactivation Domains: From Gal4 to p53.

PubMed

Piskacek, Martin; Havelka, Marek; Rezacova, Martina; Knight, Andrea

2016-01-01

The family of the Nine amino acid Transactivation Domain, 9aaTAD family, comprises currently over 40 members. The 9aaTAD domains are universally recognized by the transcriptional machinery from yeast to man. We had identified the 9aaTAD domains in the p53, Msn2, Pdr1 and B42 activators by our prediction algorithm. In this study, their competence to activate transcription as small peptides was proven. Not surprisingly, we elicited immense 9aaTAD divergence in hundreds of identified orthologs and numerous examples of the 9aaTAD species' convergence. We found unforeseen similarity of the mammalian p53 with yeast Gal4 9aaTAD domains. Furthermore, we identified artificial 9aaTAD domains generated accidentally by others. From an evolutionary perspective, the observed easiness to generate 9aaTAD transactivation domains indicates the natural advantage for spontaneous generation of transcription factors from DNA binding precursors.

EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

PubMed Central

Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

2017-01-01

Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

Influence of the presence of PAHs and coal tar on naphthalene sorption in soils

NASA Astrophysics Data System (ADS)

Bayard, Rémy; Barna, Ligia; Mahjoub, Borhane; Gourdon, Rémy

2000-11-01

The mobility of the most water-soluble polynuclear aromatic hydrocarbons (PAHs) such as naphthalene in contaminated soils from manufactured gas plant (MGP) sites or other similar sites is influenced not only by the naturally occurring soil organic matter (SOM) but also, and in many cases mostly, by the nature and concentration of coal tar xenobiotic organic matter (XOM) and other PAH molecules present in the medium under various physical states. The objective of the present study was to quantify the effects of these factors using batch experiments, in order to simulate naphthalene transport in soil-tar-water systems using column experiments. Naphthalene sorption was studied in the presence of (i) solid coal tar particles, (ii) phenanthrene supplied as pure crystals, in the aqueous solution or already sorbed onto the soil, (iii) fluoranthene as pure crystals, and (iv) an aqueous solution of organic molecules extracted from a liquid tar. All experiments were conducted under abiotic conditions using short naphthalene/sorbent contact times of 24-60 h. Although these tests do not reflect true equilibrium conditions which usually take more time to establish, they were used to segregate relatively rapid sorption phenomena ("pseudo equilibrium") from slow sorption and other aging phenomena. For longer contact times, published data have shown that experimental biases due to progressive changes in the characteristics of the soil and the solution may drastically modify the affinity of the solutes for the soil. Slow diffusion in the microporosity and in dense organic phases may also become significant over the long term, along with some irreversible aging phenomena which have not been addressed in this work. Results showed that PAHs had no effect on naphthalene sorption when present in the aqueous solution or as pure crystals, due to their low solubility in water. Adsorbed phenanthrene was found to reduce naphthalene adsorption only when present at relatively high concentrations (about 120 mg/kg) in the soil. In contrast, experiments carried out with coal tar particles revealed a significant effect. Naphthalene sorption appeared to be proportional to the amount of coal tar added to the sand or soil, and a much higher affinity of naphthalene for XOM ( Koc above 2000 cm 3/g) than SOM ( Koc around 300 cm 3/g) was observed. Naphthalene transport in the columns of sand or soil spiked with coal tar particles was simulated very satisfactorily with a dual double-domain model. Around 90% of naphthalene retention by coal tar was found to occur within the organic phase, suggesting a phase partition process which may be explained by the amorphous nature of the XOM and its extreme affinity for naphthalene. For SOM, however, which is present as porous microaggregates of clay and humic substances, with less affinity for naphthalene, only 1/3 of naphthalene retention was found to occur within the organic phase, underlining the significant role of surface adsorption in the short term behavior of naphthalene in soil. For longer contact times, the model simulations proposed in the present study should be coupled to slow sorption, aging and biodegradation models to describe long-term behavior of naphthalene in soil-tar-water systems.

Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).

PubMed

Gachon, F; Thebault, S; Peleraux, A; Devaux, C; Mesnard, J M

2000-05-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

Possible involvement of pregnane X receptor–enhanced CYP24 expression in drug-induced osteomalacia

PubMed Central

Pascussi, Jean Marc; Robert, Agnes; Nguyen, Minh; Walrant-Debray, Odile; Garabedian, Michèle; Martin, Pascal; Pineau, Thierry; Saric, Jean; Navarro, Fréderic; Maurel, Patrick; Vilarem, Marie Josè

2005-01-01

Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D3-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16α-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16α-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D3. Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between –326 and –142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D–responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D3 hormonal activity and calcium homeostasis through the activation of PXR. PMID:15630458

High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling

PubMed Central

Han, Xiao; Guo, Jinhai; Deng, Weiwei; Zhang, Chenying; Du, Peige; Shi, Taiping; Ma, Dalong

2008-01-01

Background Estrogen receptor α (ERα) is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE) with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131) as a repressor of ERα mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ERα in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERα interrupts or prevents ERα binding to the estrogen response element (ERE). In addition, ZNF131 was able to suppress the expression of pS2, an ERα target gene. Conclusion We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ERα-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ERα regulation in mammalian cells. PMID:18847501

Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)

PubMed Central

Gachon, Frederic; Thebault, Sabine; Peleraux, Annick; Devaux, Christian; Mesnard, Jean-Michel

2000-01-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation. PMID:10779337

46 CFR Table II to Part 150 - Grouping of Cargoes

Code of Federal Regulations, 2013 CFR

2013-10-01

... solutions Clay slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid, Diethanolamine salt...) Caramel solutions Clay slurry Coal slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid... Coal tar, high temperature Coal tar pitch Decahydronaphthalene Degummed C9 (DOW) Diphenyl, Diphenyl...

48 CFR 1202.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... “procuring activity.” Contracting officer (CO) means an individual authorized by virtue of their position or... Transportation Acquisition Regulation (TAR) and Transportation Acquisition Manual (TAM). Department of... Administration (FAA); (FAA is exempt from FAR, TAR and TAM pursuant to the Department of Transportation and...

48 CFR 1202.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... “procuring activity.” Contracting officer (CO) means an individual authorized by virtue of their position or... Transportation Acquisition Regulation (TAR) and Transportation Acquisition Manual (TAM). Department of... Administration (FAA); (FAA is exempt from FAR, TAR and TAM pursuant to the Department of Transportation and...

48 CFR 1202.1 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... “procuring activity.” Contracting officer (CO) means an individual authorized by virtue of their position or... Transportation Acquisition Regulation (TAR) and Transportation Acquisition Manual (TAM). Department of... Administration (FAA); (FAA is exempt from FAR, TAR and TAM pursuant to the Department of Transportation and...

48 CFR 1202.1 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... “procuring activity.” Contracting officer (CO) means an individual authorized by virtue of their position or... Transportation Acquisition Regulation (TAR) and Transportation Acquisition Manual (TAM). Department of... Administration (FAA); (FAA is exempt from FAR, TAR and TAM pursuant to the Department of Transportation and...

48 CFR 1202.1 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... “procuring activity.” Contracting officer (CO) means an individual authorized by virtue of their position or... Transportation Acquisition Regulation (TAR) and Transportation Acquisition Manual (TAM). Department of... Administration (FAA); (FAA is exempt from FAR, TAR and TAM pursuant to the Department of Transportation and...

Understanding the fate and transport of petroleum hydrocarbons from coal tar within gasholders.

PubMed

Coulon, Frédéric; Orsi, Roberto; Turner, Claire; Walton, Chris; Daly, Paddy; Pollard, Simon J T

2009-02-01

Coal tars have been identified as posing a threat to human health due to their toxic, mutagenic and carcinogenic characteristics. Workers involved in former gasholders decommissioning are potentially exposed to relevant concentrations of volatile and semi-volatile hydrocarbons upon opening up derelict tanks and during tar excavation/removal. While information on contaminated sites air-quality and its implications on medium-long term exposure is available, acute exposure issues associated with the execution of critical tasks are less understood. Calculations indicated that the concentration of a given contaminant in the gasholder vapour phase only depends on the coal tar composition, being only barely affected by the presence of water in the gasholder and the tar volume/void space ratio. Fugacity modelling suggested that risk-critical compounds such as benzene, naphthalene and other monocyclic and polycyclic aromatic hydrocarbons may gather in the gasholder air phase at significant concentrations. Gasholder emissions were measured on-site and compared with the workplace exposure limits (WELs) currently in use in UK. While levels for most of the toxic compounds were far lower than WELs, benzene air-concentrations where found to be above the accepted threshold. In addition due to the long exposure periods involved in gasholder decommissioning and the significant contribution given by naphthalene to the total coal tar vapour concentration, the adoption of a WEL for naphthalene may need to be considered to support operators in preventing human health risk at the workplace. The Level I fugacity approach used in this study demonstrated its suitability for applications to sealed environments such as gasholders and its further refining could provide a useful tool for land remediation risk assessors.

Comprehensive GC²/MS for the monitoring of aromatic tar oil constituents during biodegradation in a historically contaminated soil.

PubMed

Vasilieva, Viktoriya; Scherr, Kerstin E; Edelmann, Eva; Hasinger, Marion; Loibner, Andreas P

2012-02-20

The constituents of tar oil comprise a wide range of physico-chemically heterogeneous pollutants of environmental concern. Besides the sixteen polycyclic aromatic hydrocarbons defined as priority pollutants by the US-EPA (EPA-PAHs), a wide range of substituted (NSO-PAC) and alkylated (alkyl-PAC) aromatic tar oil compounds are gaining increased attention for their toxic, carcinogenic, mutagenic and/or teratogenic properties. Investigations on tar oil biodegradation in soil are in part hampered by the absence of an efficient analytical tool for the simultaneous analysis of this wide range of compounds with dissimilar analytical properties. Therefore, the present study sets out to explore the applicability of comprehensive two-dimensional gas chromatography (GC²/MS) for the simultaneous measurement of compounds with differing polarity or that are co-eluting in one-dimensional systems. Aerobic tar oil biodegradation in a historically contaminated soil was analyzed over 56 days in lab-scale bioslurry tests. Forty-three aromatic compounds were identified with GC²/MS in one single analysis. The number of alkyl chains on a molecule was found to prime over alkyl chain length in hampering compound biodegradation. In most cases, substitution of carbon with nitrogen and oxygen was related to increased compound degradation in comparison to unalkylated and sulphur- or unsubstituted PAH with a similar ring number.The obtained results indicate that GC²/MS can be employed for the rapid assessment of a large variety of structurally heterogeneous environmental contaminants. Its application can contribute to facilitate site assessment, development and control of microbial cleanup technologies for tar oil contaminated sites. Copyright © 2011 Elsevier B.V. All rights reserved.

Outcome of total arch replacement with coronary artery bypass grafting.

PubMed

Takashima, Noriyuki; Suzuki, Tomoaki; Asai, Tohru; Nota, Hiromitsu; Ikegami, Hirohisa; Kinoshita, Takeshi; Fujino, Susumu; Hosoba, Soh

2015-06-01

There are few reports on the outcome of total arch replacement (TAR) with concomitant coronary artery bypass grafting (CABG); the present study was aimed at analysing outcomes after TAR with CABG at our institute. Between January 2002 and December 2012, 123 consecutive patients underwent elective TAR with or without CABG. The patients were divided into two groups: 46 who had concomitant CABG (Group T/C) and the rest, who had TAR only (Group T). TAR was performed under mild hypothermic circulatory arrest and selective antegrade cerebral perfusion (SACP) using a four-branched arch graft. The number with a low ejection fraction (<50%) was higher in Group T/C, in which the additive and the logistic EuroSCORE were also higher. The mean number of coronary anastomoses was 1.6 ± 0.8 in Group T/C. The mean durations of surgery (P < 0.01), cardiopulmonary bypass (P < 0.01), cardiac ischaemia (P < 0.01) and SACP (P < 0.01) were significantly longer in Group T/C. The early graft patency of bypass grafts was 96.7%. Between Group T and Group T/C, there were no significant differences in the incidence of stroke (3.9 and 10.9%, P = 0.13), perioperative myocardial infarction (0 and 2.2%, P = 0.37) and in-hospital mortality (2.6 and 8.7%, P = 0.14). There was one case of 30-day mortality in each group. Preoperative haemodialysis, NYHA III/IV and operation time were multivariate predictors (P < 0.05) of in-hospital mortality. Although concomitant CABG in TAR patients had higher operative risk, it can be safely performed with favourable outcomes. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene expression of human immunodeficiency virus type 1 involves its negative regulatory functions.

PubMed Central

Oelze, I; Rittner, K; Sczakiel, G

1994-01-01

Adeno-associated virus type 2 (AAV-2), a human parvovirus which is apathogenic in adults, inhibits replication and gene expression of human immunodeficiency virus type 1 (HIV-1) in human cells. The rep gene of AAV-2, which was shown earlier to be sufficient for this negative interference, also down-regulated the expression of heterologous sequences driven by the long terminal repeat (LTR) of HIV-1. This effect was observed in the absence of the HIV-1 transactivator Tat, i.e., at basal levels of LTR-driven transcription. In this work, we studied the involvement of functional subsequences of the HIV-1 LTR in rep-mediated inhibition in the absence of Tat. Mutated LTRs driving an indicator gene (cat) were cointroduced into human SW480 cells together with rep alone or with double-stranded DNA fragments or RNA containing sequences of the HIV-1 LTR. The results indicate that rep strongly enhances the function of negative regulatory elements of the LTR. In addition, the experiments revealed a transcribed sequence element located within the TAR-coding sequence termed AHHH (AAV-HIV homology element derived from HIV-1) which is involved in rep-mediated inhibition. The AHHH element is also involved in down-regulation of basal expression levels in the absence of rep, suggesting that AHHH also contributes to negative regulatory functions of the LTR of HIV-1. In contrast, positive regulatory elements of the HIV-1 LTR such as the NF kappa B and SP1 binding sites have no significant influence on the rep-mediated inhibition. Images PMID:8289357

Neutrophil elastase enhances IL-12p40 production by lipopolysaccharide-stimulated macrophages via transactivation of the PAR-2/EGFR/TLR4 signaling pathway.

PubMed

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

2016-07-01

Proteinase-activated receptor 2 (PAR-2) and toll-like receptor 4 (TLR4) are involved in innate immune responses and signaling cross-talk between these receptor molecules has the potential to augment an ongoing inflammatory response. The aim of this study was to evaluate the possible cooperative influence of PAR-2 and TLR4 on IL-12p40 production by macrophages after stimulation with lipopolysaccharide (LPS). During culture, GM-CSF upregulated PAR-2 expression by macrophages in a time-dependent manner. Stimulation with LPS enhanced IL-12p40 production by macrophages in a concentration-dependent manner. While human neutrophil elastase (HNE) did not induce IL-12p40 production, pretreatment of macrophages with HNE synergistically increased the IL-12p40 protein level after LPS exposure. Silencing of TLR4 with small interfering RNA blunted the synergistic enhancement of IL-12p40 by HNE combined with LPS. Silencing of β-arrestin 2, p22phox, or ERK1/2 also inhibited an increase of IL-12p40. Interestingly, transfection of macrophages with small interfering RNA duplexes for DUOX-2, EGFR, TLR4, or TRAF6 significantly blunted the increase of IL-12p40 in response to treatment with HNE plus LPS. U73122 and Rottlerin also inhibited the increased production of IL-12p40. In conclusion, HNE is involved in transactivation of TLR4 through activation of DUOX-2/EGFR and synergistically enhances IL-12p40 production by macrophages stimulated with LPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Intrinsic hyporesponsiveness of invariant natural killer T cells precedes the onset of lupus

PubMed Central

Yang, J-Q; Kim, P J; Halder, R C; Singh, R R

2013-01-01

Patients with systemic lupus erythematosus (SLE) display reduced numbers and functions of invariant natural killer T (iNK T) cells, which are restored upon treatment with corticosteroids and rituximab. It is unclear whether the iNK T cell insufficiency is a consequence of disease or is a primary abnormality that precedes the onset of disease. To address this, we analysed iNK T cell function at different stages of disease development using the genetically lupus-susceptible NZB × NZW F1 (BWF1) model. We found that iNK T cell in-vivo cytokine responses to an iNK T cell ligand α-galactosylceramide (α-GalCer) were lower in BWF1 mice than in non-autoimmune BALB/c and major histocompatibility complex (MHC)-matched NZB × N/B10.PL F1 mice, although iNK T cell numbers in the periphery were unchanged in BWF1 mice compared to control mice. Such iNK T cell hyporesponsiveness in BWF1 mice was detected at a young age long before the animals exhibited any sign of autoimmunity. In-vivo activation of iNK T cells is known to transactivate other immune cells. Such transactivated T and B cell activation markers and/or cytokine responses were also lower in BWF1 mice than in BALB/c controls. Finally, we show that iNK T cell responses were markedly deficient in the NZB parent but not in NZW parent of BWF1 mice, suggesting that BWF1 might inherit the iNK T cell defect from NZB mice. Thus, iNK T cells are functionally insufficient in lupus-prone BWF1 mice. Such iNK T cell insufficiency precedes the onset of disease and may play a pathogenic role during early stages of disease development in SLE. PMID:23607366

EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences.

PubMed

Monti, Paola; Russo, Debora; Bocciardi, Renata; Foggetti, Giorgia; Menichini, Paola; Divizia, Maria T; Lerone, Margherita; Graziano, Claudio; Wischmeijer, Anita; Viadiu, Hector; Ravazzolo, Roberto; Inga, Alberto; Fronza, Gilberto

2013-06-01

TP63 germ-line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm-derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA-binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild-type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN-P63α-specific REs derived from genes closely related to the clinical manifestations of the TP63-associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability. © 2013 Wiley Periodicals, Inc.

A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages.

PubMed

Ma, Shibin; Ming, Zhenping; Gong, Ai-Yu; Wang, Yang; Chen, Xiqiang; Hu, Guoku; Zhou, Rui; Shibata, Annemarie; Swanson, Patrick C; Chen, Xian-Ming

2017-03-01

Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. We report here that the lincRNA gene lincRNA-Tnfaip3 , located at mouse chromosome 10 proximal to the tumor necrosis factor α-induced protein 3 ( Tnfaip3 ) gene, is an early-primary response gene controlled by nuclear factor-κB (NF-κB) signaling in murine macrophages. Functionally, lincRNA- Tnfaip3 appears to mediate both the activation and repression of distinct classes of inflammatory genes in macrophages. Specifically, induction of lincRNA-Tnfaip3 is required for the transactivation of NF-κB-regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA-Tnfaip3 physically interacts with the high-mobility group box 1 (Hmgb1), assembling a NF-κB/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation. This resultant NF-κB/Hmgb1/lincRNA-Tnfaip3 complex can modulate Hmgb1-associated histone modifications and, ultimately, transactivation of inflammatory genes in mouse macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role of NF-κB-induced lincRNA-Tnfaip3 to act as a coactivator of NF-κB for the transcription of inflammatory genes in innate immune cells through modulation of epigenetic chromatin remodeling.-Ma, S., Ming, Z., Gong, A.-Y., Wang, Y., Chen, X., Hu, G., Zhou, R., Shibata, A., Swanson, P. C., Chen, X.-M. A long noncoding RNA, LincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages. © FASEB.

Key learnings from performance of the U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 in vitro assays.

PubMed

LeBaron, Matthew J; Coady, Katie K; O'Connor, John C; Nabb, Diane L; Markell, Lauren K; Snajdr, Suzanne; Sue Marty, M

2014-02-01

Tier 1 of the U.S. EPA Endocrine Disruptor Screening Program comprises 11 studies: five in vitro assays, four in vivo mammalian assays, and two in vivo nonmammalian assays. The battery is designed to detect compounds with the potential to interact with the estrogen, androgen, or thyroid signaling pathways. This article examines the procedures, results, and data interpretation for the five Tier 1 in vitro assays: estrogen receptor (ER) and androgen receptor binding assays, an ER transactivation assay, an aromatase assay, and a steroidogenesis assay. Data are presented from two laboratories that have evaluated approximately 11 compounds in the Tier 1 in vitro assays. Generally, the ER and androgen receptor binding assays and the aromatase assay showed good specificity and reproducibility. As described in the guideline for the ER transactivation assay, a result is considered positive when the test compound induces a reporter gene signal that reaches 10% of the response seen with 1 nM 17β-estradiol (positive control). In the experience of these laboratories, this cutoff criterion may result in false-positive responses. For the steroidogenesis assay, there is variability in the basal and stimulated production of testosterone and estradiol by the H295R cells. This variability in responsiveness, coupled with potential cell stress at high concentrations of test compound, may make it difficult to discern whether hormone alterations are specific steroidogenesis alterations (i.e., endocrine active). Lastly, both laboratories had difficulty meeting some recommended performance criteria for each Tier 1 in vitro assay. Data with only minor deviations were deemed valid. © 2014 Wiley Periodicals, Inc.

46 CFR Table II to Part 150 - Grouping of Cargoes

Code of Federal Regulations, 2014 CFR

2014-10-01

... solutions Clay slurry Corn syrup Dextrose solution 2,4-Dichlorophenoxyacetic acid, Diethanolamine salt... lignosulfonate solution (free alkali content 1% or less) Caramel solutions Clay slurry Coal slurry Corn syrup... Coal tar, high temperature Coal tar pitch Decahydronaphthalene Degummed C9 (DOW) Diphenyl, Diphenyl...

Microplastic and tar pollution on three Canary Islands beaches: An annual study.

PubMed

Herrera, A; Asensio, M; Martínez, I; Santana, A; Packard, T; Gómez, M

2018-04-01

Marine debris accumulation was analyzed from three exposed beaches of the Canary Islands (Lambra, Famara and Las Canteras). Large microplastics (1-5mm), mesoplastics (5-25mm) and tar pollution were assessed twice a month for a year. There was great spatial and temporal variability in the Canary Island coastal pollution. Seasonal patterns differed at each location, marine debris concentration depended mainly of local-scale wind and wave conditions. The most polluted beach was Lambra, a remote beach infrequently visited. The types of debris found were mainly preproduction resin pellets, plastic fragments and tar, evidencing that pollution was not of local origin, but it cames from the open sea. The levels of pollution were similar to those of highly industrialized and contaminated regions. This study corroborates that the Canary Islands are an area of accumulation of microplastics and tar rafted from the North Atlantic Ocean by the southward flowing Canary Current. Copyright © 2017 Elsevier Ltd. All rights reserved.

Superfund Record of Decision (EPA Region 5): Reilly Tar and Chemical Corporation Site, St. Peter Aquifer, St. Louis Park, MN. (Third remedial action), September 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-09-28

The 80-acre Reilly Tar and Chemical (St. Louis Park) site is a former coal tar distillation and wood preserving plant in St. Louis Park, Minnesota. The site overlies a complex system of aquifers, including the St. Peter aquifer that provide drinking water to area residences. The St. Peter Aquifer contains one municipal well, which is used during periods of peak demand, however, the majority of the drinking water in St. Louis Park is obtained from deeper aquifers. From 1917 to 1972, wastewater containing creosote and coal tar was discharged to onsite surface water, and as a result, small wastewater spillsmore » occurred into onsite soil. The ROD addresses Operable Unit 4 (OU4), remediation of the St. Peter aquifer. A subsequent ROD will address any remaining site problems as OU3. The primary contaminants of concern affecting the ground water are organics including PAHs and phenols.« less