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Sample records for ahr active chemicals

  1. The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction

    PubMed Central

    Vacca, Margherita; Nardelli, Claudia; Castegna, Alessandra; Arnesano, Fabio; Carella, Nicola; Depalo, Raffaella

    2016-01-01

    Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb. PMID:27008165

  2. A maternal Ahr null genotype sensitizes embryos to chemical teratogenesis.

    PubMed

    Thomae, Tami L; Glover, Edward; Bradfield, Christopher A

    2004-07-16

    The aryl hydrocarbon receptor (encoded by the Ahr locus) is a ligand-activated transcription factor that mediates the toxicology and teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). In an effort to understand the role of the maternal compartment in dioxin teratology, we designed a breeding strategy that allowed us to compare the teratogenic response in embryos from Ahr(-/-) (null) and Ahr(+/+) (wild-type) dams. Using this strategy, we demonstrate that embryos from the Ahr(-/-) dams are 5-fold more sensitive to dioxin-induced cleft palate and hydronephrosis as compared with embryos from an Ahr(+/+) dam. Moreover, this increased teratogenic sensitivity extends beyond dioxin, because embryos from Ahr(-/-) dams exhibited a 9-fold increase in their sensitivity to the fetotoxic effects of the glucocorticoid, dexamethasone. In searching for an explanation for this increased sensitivity, we found that more dioxin and dexamethasone reached the embryos from Ahr(-/-) dams as compared with embryos from Ahr(+/+) dams. We propose that increased deposition of teratogens/fetotoxicants to the embryonic compartment is the result of porto-systemic shunting and/or blocked P4501A induction in Ahr(-/-) dams. In addition to demonstrating the importance of maternal AHR in teratogenesis, these data may have implications that reach beyond the mechanism of action of dioxin. In this regard, the Ahr(-/-) mouse may provide a system that allows pharmacological agents and toxicants to be more easily studied in a model where first pass clearance is a significant obstacle.

  3. Teratogenic impact of dioxin-activated AHR in laboratory animals

    EPA Science Inventory

    AHR and ARNT are expressed in mouse and human palatal shelves and in the urinary tract of the mouse fetus. AHR expression, translocation to the nucleus, binding to DRE, and activation are required for mediation of TCDD-induction of CP and HN. Although the human palate requires a ...

  4. AhR activation underlies the CYP1A autoinduction by A-998679 in rats

    PubMed Central

    Liguori, Michael J.; Lee, Chih-Hung; Liu, Hong; Ciurlionis, Rita; Ditewig, Amy C.; Doktor, Stella; Andracki, Mark E.; Gagne, Gerard D.; Waring, Jeffrey F.; Marsh, Kennan C.; Gopalakrishnan, Murali; Blomme, Eric A. G.; Yang, Yi

    2012-01-01

    Xenobiotic-mediated induction of cytochrome P450 (CYP) drug metabolizing enzymes (DMEs) is frequently encountered in drug discovery and can influence disposition, pharmacokinetic, and toxicity profiles. The CYP1A subfamily of DMEs plays a central role in the biotransformation of several drugs and environmental chemicals. Autoinduction of drugs through CYP3A enzymes is a common mechanism for their enhanced clearance. However, autoinduction via CYP1A is encountered less frequently. In this report, an experimental compound, A-998679 [3-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl) benzonitrile], was shown to enhance its own clearance via induction of Cyp1a1 and Cyp1a2. Rats were dosed for 5 days with 30, 100, and 200 mg/kg/day A-998679. During the dosing period, the compound's plasma AUC decreased at 30 mg/kg (95%) and 100 mg/kg (80%). Gene expression analysis and immunohistochemistry of the livers showed a large increase in the mRNA and protein levels of Cyp1a, which was involved in the biotransformation of A-998679. Induction of CYP1A was confirmed in primary rat, human, and dog hepatocytes. The compound also weakly inhibited CYP1A2 in human liver microsomes. A-998679 activated the aryl hydrocarbon receptor (AhR) in a luciferase gene reporter assay in HepG2 cells, upregulated expression of genes associated with AhR activation in rat liver and enhanced nuclear migration of AhR in HepG2 cells. Collectively these results demonstrate that A-998679 is an AhR activator that induces Cyp1a1 and Cyp1a2 expression, resulting in an autoinduction phenomenon. The unique properties of A-998679, along with its novel structure distinct from classical polycyclic aromatic hydrocarbons (PAHs), may warrant its further evaluation as a tool compound for use in studies involving AhR biology and CYP1A-related mechanisms of drug metabolism and toxicity. PMID:23112805

  5. The Role of AhR in Breast Cancer Development

    DTIC Science & Technology

    2006-07-01

    other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen-responsive transcription factor...constitutively active AhR. Constitutive and environmental chemical-inducible AhR activity was profoundly suppressed by galangin as was cell growth...However, the failure of a-naphthoflavone or FhAhRR transfection to block growth indicated that galangin -mediated AhR inhibition was either insufficient

  6. The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90

    PubMed Central

    Tsuji, Noriko; Fukuda, Kana; Nagata, Yuhtaroh; Okada, Hirotaka; Haga, Asami; Hatakeyama, Shiori; Yoshida, Shiho; Okamoto, Tomoya; Hosaka, Miki; Sekine, Kazuhiro; Ohtaka, Kei; Yamamoto, Soh; Otaka, Michiro; Grave, Ewa; Itoh, Hideaki

    2014-01-01

    The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15 min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90. We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8 h after treatment with β-NF. PMID:25349783

  7. Combined chemical and toxicological long-term monitoring for AhR agonists with SPMD-based virtual organisms in drinking water Danjiangkou Reservoir, China.

    PubMed

    Wang, Jingxian; Song, Guoqiang; Li, Aimin; Henkelmann, Bernhard; Pfister, Gerd; Tong, Anthony Z; Schramm, Karl-Werner

    2014-08-01

    SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources.

  8. A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

    PubMed Central

    Regazzo, Daniela; Bertazza, Loris; Galuppini, Francesca; Guzzardo, Vincenza; Jaffrain-Rea, Marie Lise; Vianello, Federica; Ciato, Denis; Ceccato, Filippo; Watutantrige-Fernando, Sara; Bisognin, Andrea; Bortoluzzi, Stefania; Pennelli, Gianmaria; Boscaro, Marco; Scaroni, Carla; Mian, Caterina

    2015-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice. PMID:26392334

  9. A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC.

    PubMed

    Occhi, Gianluca; Barollo, Susi; Regazzo, Daniela; Bertazza, Loris; Galuppini, Francesca; Guzzardo, Vincenza; Jaffrain-Rea, Marie Lise; Vianello, Federica; Ciato, Denis; Ceccato, Filippo; Watutantrige-Fernando, Sara; Bisognin, Andrea; Bortoluzzi, Stefania; Pennelli, Gianmaria; Boscaro, Marco; Scaroni, Carla; Mian, Caterina

    2015-10-13

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAFV600E may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice.

  10. Characterization of AhR agonists reveals antagonistic activity in European herring gull (Larus argentatus) eggs.

    PubMed

    Muusse, Martine; Christensen, Guttorm; Gomes, Tânia; Kočan, Anton; Langford, Katherine; Tollefsen, Knut Erik; Vaňková, Lenka; Thomas, Kevin V

    2015-05-01

    European herring gull (Larus argentatus) eggs from two Norwegian islands, Musvær in the south east and Reiaren in Northern Norway, were screened for dioxins, furans, and dioxin-like and selected non-dioxin-like polychlorinated biphenyls (PCBs), and subjected to non-target analysis to try to identify the aryl hydrocarbon receptor (AhR) agonists, responsible for elevated levels measured using the dioxin responsive chemically activated luciferase expression (DR-CALUX) assay. Eggs from Musvær contained chemically calculated toxic equivalent (WHO TEQ) levels of between 109 and 483 pg TEQ/g lw, and between 82 and 337 pg TEQ/g lw was determined in eggs from Reiaren. In particular PCB126 contributed highly to the total TEQ (69-82%). In 19 of the 23 samples the calculated WHO TEQ was higher than the TEQCALUX. Using CALUX specific relative effect potencies (REPs), the levels were lower at between 77 and 292 pg/g lw in eggs from Musvær and between 55 and 223 pg/g lw in eggs from Reiaren, which was higher than the TEQCALUX in 16 of the 23 samples. However, the means of the REP values and the TEQCALUX were not significantly different. This suggests the presence of compounds that can elicit antagonist effects, with a low binding affinity to the AhR. Non-target analysis identified the presence of hexachlorobenzene (HCB) (quantified at 9.6-185 pg/g lw) but neither this compound nor high concentrations of PCB126 and non-dioxin-like PCBs could explain the differences between the calculated TEQ or REP values and the TEQCALUX. Even though, for most AhR agonists, the sensitivity of herring gulls is not known, the reported levels can be considered to represent a risk for biological effects in the developing embryo, compared to LC50 values in chicken embryos. For human consumers of herring gull eggs, these eggs contain TEQ levels up to four times higher than the maximum tolerable weekly intake.

  11. A binding site for activation by the Bacillus subtilis AhrC protein, a repressor/activator of arginine metabolism.

    PubMed

    Klingel, U; Miller, C M; North, A K; Stockley, P G; Baumberg, S

    1995-08-21

    In Bacillus subtilis, the AhrC protein represses genes encoding enzymes of arginine biosynthesis and activates those mediating its catabolism. To determine how this repressor also functions as an activator, we attempted to clone catabolic genes by searching for insertions of the Tn917-lacZ transposon that express AhrC-dependent, arginine-inducible beta-galactosidase activity. One such isolate was obtained. The region upstream of lacZ was subcloned in Escherichia coli in such a way that it could be replaced in the B. subtilis chromosome after appropriate manipulation. Analysis of exonuclease III-derived deletions located an AhrC-dependent, arginine-inducible promoter to within a ca. 1.9 kb fragment. The sequence revealed: the 3' end of an ORF homologous to gdh genes encoding glutamate dehydrogenase, with highest homology to the homologue from Clostridium difficile; the 5' end of an ORF homologous to a Saccharomyces cerevisiae gene encoding delta 1-pyrroline 5-carboxylate dehydrogenase (P5CDH), an enzyme of arginine catabolism; and just upstream of the latter, a sequence with homology to known AhrC binding sites in the upstream part of the biosynthetic argCJBD-cpa-F cluster. The same region has also been sequenced by others as part of the B. subtilis genome sequencing project, revealing that the P5CDH gene is the first in a cluster termed rocABC. Restriction fragments containing the putative AhrC-binding sequence, but not those lacking it, showed retarded electrophoretic mobility in the presence of purified AhrC. A 277 bp AhrC-binding fragment also showed anomalous mobility in the absence of AhrC, consistent with its being intrinsically bent. DNAse I footprinting localized AhrC binding to bp -16/-22 to +1 (the transcription startpoint). Such a location for an activator binding site, i.e. overlapping the transcription start, is unusual.

  12. Effects of scorched food leachates with or without activated charcoal pretreatment on AhR activation in cultured cells.

    PubMed

    Takahashi, Satoshi; Morita, Koji; Kinoshita, Makoto; Fujimori, Shin; Ishikawa, Toshio

    2015-12-01

    Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health.

  13. 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.

  14. Constitutive AhR activation leads to concomitant ABCG2-mediated multidrug resistance in cisplatin-resistant esophageal carcinoma cells.

    PubMed

    To, Kenneth K W; Yu, Le; Liu, Shuwen; Fu, Jianhua; Cho, Chi Hin

    2012-06-01

    Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that is generally not responding to chemotherapy. It is particularly predominant in China. Although ESCC is significantly associated with cigarette smoking, the relationship between its molecular pathogenesis and responsiveness to chemotherapy and cigarette smoke remains elusive. This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17-AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2-mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer.

  15. Benzo[ghi]perylene activates the AHR pathway to exert biological effects on the NL-20 human bronchial cell line.

    PubMed

    Zaragoza-Ojeda, Montserrat; Eguía-Aguilar, Pilar; Perezpeña-Díazconti, Mario; Arenas-Huertero, Francisco

    2016-08-10

    Polycyclic aromatic hydrocarbons (PAH) are produced by incomplete combustion of organic material. In the Mexico City atmosphere, the most abundant PAH is benzo[ghi]perylene (BghiP), a gasoline combustion marker. At present, there are no reports of the effects of BghiP on human bronchial cells, so the aim of the study was to evaluate the effects in vitro of BghiP on the NL-20 cell line. Results showed that BghiP induced the formation of small vesicles throughout the cytoplasm, with absence of nuclear fragmentation. At 48h exposition, damage in cell membrane increased significantly at 1.24μg/mL of BghiP (p<0.05). Immunocytochemistry revealed that BghiP provokes nuclear translocation of AhR receptor, which indicates that this compound can induce transcription of genes via receptor binding (AhR pathway activation). BghiP induced a two-fold increase (p<0.05) in the expression of AhR and CYP4B1 (a lung-specific pathway effector). In the presence of the receptor antagonist CH-223191, the loss of viability, the nuclear translocation and the overexpression of genes decreased, though this did not prevent the formation of vesicles. BghiP induced oxidative stress and in presence of the receptor antagonist this increased significantly. In conclusion, BghiP can activate the overexpression of AhR and CYP4B1, and the effects are abated by the AhR receptor antagonist. This is the first report to prove that BghiP utilizes the AhR pathway to exert its toxic effects on the NL-20 human bronchial cell line .

  16. Exposure to Diesel Exhaust Particle Extracts (DEPe) Impairs Some Polarization Markers and Functions of Human Macrophages through Activation of AhR and Nrf2

    PubMed Central

    Jaguin, Marie; Fardel, Olivier; Lecureur, Valérie

    2015-01-01

    Macrophages (MΦ), well-known to play an important role in immune response, also respond to environmental toxic chemicals such as diesel exhaust particles (DEP). Potential effects of DEPs towards MΦ polarization, a key hall-mark of MΦ physiology, remain however poorly documented. This study was therefore designed to evaluate the effects of a reference DEP extract (DEPe) on human MΦ polarization. Human blood monocytes-derived MΦ were incubated with IFNγ+LPS or IL-4 to obtain M1 and M2 subtypes, respectively; a 24 h exposure of polarizing MΦ to 10 μg/ml DEPe was found to impair expression of some macrophagic M1 and M2 markers, without however overall inhibition of M1 and M2 polarization processes. Notably, DEPe treatment increased the secretion of the M1 marker IL-8 and the M2 marker IL-10 in both MΦ subtypes, whereas it reduced lipopolysaccharide-induced IL-6 and IL-12p40 secretion in M1 MΦ. In M2 MΦ, DEPe exposure led to a reduction of CD200R expression and of CCL17, CCL18 and CCL22 secretion, associated with a lower chemotaxis of CCR4-positive cells. DEPe activated the Nrf2 and AhR pathways and induced expression of their reference target genes such as Hmox-1 and cytochrome P-4501B1 in M1 and M2 MΦ. Nrf2 or AhR silencing through RNA interference prevented DEPe-related down-regulation of IL-6. AhR silencing also inhibited the down-secretion of IL-12p40 and CCL18 in M1- and M2-DEPe-exposed MΦ, respectively. DEPs are therefore likely to alter expression of some M1 and M2 markers in an AhR- and Nrf2-dependent manner; such regulations may contribute to deleterious immune effects of atmospheric DEP. PMID:25710172

  17. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    PubMed Central

    Ghotbaddini, Maryam; Powell, Joann B.

    2015-01-01

    The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models. PMID:26154658

  18. AhR signaling activation disrupts migration and dendritic growth of olfactory interneurons in the developing mouse

    PubMed Central

    Kimura, Eiki; Ding, Yunjie; Tohyama, Chiharu

    2016-01-01

    Perinatal exposure to a low level of dioxin, a ubiquitous environmental pollutant, has been shown to induce abnormalities in learning and memory, emotion, and sociality in laboratory animals later in adulthood. However, how aryl hydrocarbon receptor (AhR) signaling activation disrupts the higher brain function remains unclear. Therefore, we studied the possible effects of excessive activation of AhR signaling on neurodevelopmental processes, such as cellular migration and neurite growth, in mice. To this end, we transfected a constitutively active-AhR plasmid into stem cells in the lateral ventricle by in vivo electroporation on postnatal day 1. Transfection was found to induce tangential migration delay and morphological abnormalities in neuronal precursors in the rostral migratory stream at 6 days post-electroporation (dpe) as well as disrupt radial migration in the olfactory bulb and apical and basal dendritic growth of the olfactory interneurons in the granule cell layer at 13 and 20 dpe. These results suggest that the retarded development of interneurons by the excessive AhR signaling may at least in part explain the dioxin-induced abnormal behavioral alterations previously reported in laboratory animals. PMID:27197834

  19. Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/− Mice

    PubMed Central

    Boule, Lisbeth A.; Burke, Catherine G.; Fenton, Bruce M.; Thevenet-Morrison, Kelly; Jusko, Todd A.; Lawrence, B. Paige

    2015-01-01

    Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4+ T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4+ T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4+ T cells to infection later in life but whether CD4+ T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq+/− mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq+/− offspring. Developmental activation of the AHR-accelerated disease in Gnaq+/− mice, and this correlates with increases in effector CD4+ T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq+/− mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life. PMID:26363170

  20. Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/- Mice.

    PubMed

    Boule, Lisbeth A; Burke, Catherine G; Fenton, Bruce M; Thevenet-Morrison, Kelly; Jusko, Todd A; Lawrence, B Paige

    2015-12-01

    Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4(+) T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4(+) T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4(+) T cells to infection later in life but whether CD4(+) T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq(+/-) mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq(+/-) offspring. Developmental activation of the AHR-accelerated disease in Gnaq(+/-) mice, and this correlates with increases in effector CD4(+) T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq(+/-) mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life.

  1. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    SciTech Connect

    Cheng, Ya-Hsin; Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan; Hung, Chein-Hui; Chang, Nai Wen; Lin, Chingju

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  2. Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues.

    PubMed

    Lee, Sangwoo; Shin, Woong-Hee; Hong, Seongjin; Kang, Habyeong; Jung, Dawoon; Yim, Un Hyuk; Shim, Won Joon; Khim, Jong Seong; Seok, Chaok; Giesy, John P; Choi, Kyungho

    2015-11-01

    Polycyclic aromatic hydrocarbons (PAHs) and their alkylated forms are important components of crude oil. Both groups of PAHs have been reported to cause dioxin-like responses, mediated by aryl hydrocarbon receptor (AhR). Thus, characterization of binding affinity to the AhR of unsubstituted or alkylated PAHs is important to understand the toxicological consequences of oil contamination on ecosystems. We investigated the potencies of major PAHs of crude oil, e.g., chrysene, phenanthrene and dibenzothiophene, and their alkylated forms (n=17) to upregulate expression of AhR-mediated processes by use of the H4IIE-luc transactivation bioassay. In addition, molecular descriptors of different AhR activation potencies among PAHs were investigated by use of computational molecular docking models. Based on responses of the H4IIE-luc in vitro assay, it was shown that potencies of PAHs were determined by alkylation in addition to the number and conformation of rings. Potencies of AhR-mediated processes were generally greater when a chrysene group was substituted, especially in 1-methyl-chrysene. Significant negative correlations were observed between the in vitro dioxin-like potency measured in H4IIE-luc cells and the binding distance estimated from the in silico modeling. The difference in relative potency for AhR activation observed among PAHs and their alkylated forms could be explained by differences among binding distances in the ligand binding domain of the AhR caused by alkylation. The docking model developed in the present study may have utility in predicting risks of environmental contaminants of which toxicities are mediated by AhR binding.

  3. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions

    SciTech Connect

    Wincent, Emma; Stegeman, John J.; Jönsson, Maria E.

    2015-04-15

    Wnt/β-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between β-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the β-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with β-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of β-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a β-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of β-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of β-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating β-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes.

  4. Mixed-ligand copper(II) complexes activate aryl hydrocarbon receptor AhR and induce CYP1A genes expression in human hepatocytes and human cell lines.

    PubMed

    Kubešová, Kateřina; Dořičáková, Aneta; Trávníček, Zdeněk; Dvořák, Zdeněk

    2016-07-25

    The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3·H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7-carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology.

  5. Feedback control of AHR signalling regulates intestinal immunity.

    PubMed

    Schiering, Chris; Wincent, Emma; Metidji, Amina; Iseppon, Andrea; Li, Ying; Potocnik, Alexandre J; Omenetti, Sara; Henderson, Colin J; Wolf, C Roland; Nebert, Daniel W; Stockinger, Brigitta

    2017-02-09

    The aryl hydrocarbon receptor (AHR) recognizes xenobiotics as well as natural compounds such as tryptophan metabolites, dietary components and microbiota-derived factors, and it is important for maintenance of homeostasis at mucosal surfaces. AHR activation induces cytochrome P4501 (CYP1) enzymes, which oxygenate AHR ligands, leading to their metabolic clearance and detoxification. Thus, CYP1 enzymes have an important feedback role that curtails the duration of AHR signalling, but it remains unclear whether they also regulate AHR ligand availability in vivo. Here we show that dysregulated expression of Cyp1a1 in mice depletes the reservoir of natural AHR ligands, generating a quasi AHR-deficient state. Constitutive expression of Cyp1a1 throughout the body or restricted specifically to intestinal epithelial cells resulted in loss of AHR-dependent type 3 innate lymphoid cells and T helper 17 cells and increased susceptibility to enteric infection. The deleterious effects of excessive AHR ligand degradation on intestinal immune functions could be counter-balanced by increasing the intake of AHR ligands in the diet. Thus, our data indicate that intestinal epithelial cells serve as gatekeepers for the supply of AHR ligands to the host and emphasize the importance of feedback control in modulating AHR pathway activation.

  6. Detection of Aryl Hydrocarbon Receptor Activation by Some Chemicals in Food Using a Reporter Gene Assay

    PubMed Central

    Amakura, Yoshiaki; Tsutsumi, Tomoaki; Yoshimura, Morio; Nakamura, Masafumi; Handa, Hiroshi; Matsuda, Rieko; Teshima, Reiko; Watanabe, Takahiro

    2016-01-01

    The purpose of this study was to examine whether a simple bioassay used for the detection of dioxins (DXNs) could be applied to detect trace amounts of harmful DXN-like substances in food products. To identify substances with possible DXN-like activity, we assessed the ability of various compounds in the environment to bind the aryl hydrocarbon receptor (AhR) that binds specifically to DXNs. The compounds tested included 19 polycyclic aromatic hydrocarbons (PAHs), 20 PAH derivatives (nitrated, halogenated, and aminated derivatives), 23 pesticides, six amino acids, and eight amino acid metabolites. The AhR binding activities (AhR activity) of these compounds were measured using the chemical activated luciferase gene expression (CALUX) reporter gene assay system. The majority of the PAHs exhibited marked AhR activity that increased in a concentration-dependent manner. Furthermore, there was a positive link between AhR activity and the number of aromatic rings in the PAH derivatives. Conversely, there appeared to be a negative correlation between AhR activity and the number of chlorine residues present on halogenated PAH derivatives. However, there was no correlation between AhR activity and the number and position of substituents among nitrated and aminated derivatives. Among the pesticides tested, the indole-type compounds carbendazim and thiabendazole showed high levels of activity. Similarly, the indole compound tryptamine was the only amino acid metabolite to induce AhR activity. The results are useful in understanding the identification and characterization of AhR ligands in the CALUX assay. PMID:28231110

  7. Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells.

    PubMed

    Chu, Xiao Ting; de la Cruz, Joseph; Hwang, Seong Gu; Hong, Heeok

    2014-01-01

    Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, 400 μg/mL) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

  8. Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast.

    PubMed

    Mexia, Nikitia; Gaitanis, Georgios; Velegraki, Aristea; Soshilov, Anatoly; Denison, Michael S; Magiatis, Prokopios

    2015-04-01

    Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in the human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on l-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assay in recombinant cell lines derived from four different species, although significant species differences in relative potency were observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. M. furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.

  9. Polycyclic aromatic hydrocarbons (PAHs) mediate transcriptional activation of the ATP binding cassette transporter ABCB6 gene via the aryl hydrocarbon receptor (AhR).

    PubMed

    Chavan, Hemantkumar; Krishnamurthy, Partha

    2012-09-14

    Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics.

  10. Cancer-promoting and Inhibiting Effects of Dietary Compounds: Role of the Aryl Hydrocarbon Receptor (AhR)

    PubMed Central

    Powell, Joann B.; Ghotbaddini, Maryam

    2014-01-01

    Polyaromatic hydrocarbons, heterocyclic aromatic amines and dioxin-like compounds are environmental carcinogens shown to initiate cancer in a number of tissue types including prostate and breast. These environmental carcinogens elicit their effects through interacting with the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Naturally occurring compounds found in fruits and vegetables shown to have anti-carcinogenic effects also interact with the AhR. This review explores dietary and environmental exposure to chemical carcinogens and beneficial natural compounds whose effects are elicited by the AhR. PMID:25258701

  11. Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver

    NASA Astrophysics Data System (ADS)

    Amenya, Hesbon Z.; Tohyama, Chiharu; Ohsako, Seiichiroh

    2016-10-01

    The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.

  12. Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver

    PubMed Central

    Amenya, Hesbon Z.; Tohyama, Chiharu; Ohsako, Seiichiroh

    2016-01-01

    The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress. PMID:27713569

  13. AHR-11797: a novel benzodiazepine antagonist

    SciTech Connect

    Johnson, D.N.; Kilpatrick, B.F.; Hannaman, P.K.

    1986-03-01

    AHR-11797(5,6-dihydro-6-methyl-1-phenyl-/sup 3/H-pyrrolo(3,2,1-ij)quinazolin-3-one) displaced /sup 3/H-flunitrazepam (IC/sub 50/ = 82 nM) and /sup 3/H-Ro 15-1877 (IC/sub 50/ = 104 nM) from rat brain synaptosomes. AHR-11797 did not protect mice from seizures induced by maximal electroshock or subcutaneous Metrazol (scMET), nor did it induce seizures in doses up to the lethal dose. However, at 31.6 mg/kg, IP, it significantly increased the anticonvulsant ED/sub 50/ of chlordiazepoxide (CDPX) from 1.9 to 31.6 mg/kg, IP. With 56.7 mg/kg, IP, of AHR-11797, CDPX was inactive in doses up to 100 mg/kg, IP. AHR-11797 did not significantly increase punished responding in the Geller and Seifter conflict procedure, but it did attenuate the effects of diazepam. Although the compound is without anticonvulsant or anxiolytic activity, it did have muscle relaxant properties. AHR-11797 blocked morphine-induced Straub tail in mice (ED/sub 50/ = 31 mg/kg, IP) and it selectively suppressed the polysnaptic linguomandibular reflex in barbiturate-anesthetized cats. The apparent muscle relaxant activity of AHR-11797 suggests that different receptor sites are involved for muscle relaxant vs. anxiolytic/anticonvulsant activities of the benzodiazepines.

  14. The aryl hydrocarbon receptor (AhR) pathway as a regulatory pathway for cell adhesion and matrix metabolism

    PubMed Central

    Kung, Tiffany; Murphy, K.A.; White, L.A.

    2009-01-01

    The aryl hydrocarbon receptor (AhR) is an orphan receptor in the basic-helix-loop-helix PAS family of transcriptional regulators. Although the endogenous regulator of this pathway has not been identified, the AhR is known to bind and be activated by a variety of compounds ranging from environmental contaminants to flavanoids. The function of this receptor is still unclear; however, animal models indicate that the AhR is important for normal development. One hypothesis is that the AhR senses cellular stress and initiates the cellular response by altering gene expression and inhibiting cell cycle progression and that activation of the AhR by exogenous environmental chemicals results in the dysregulation of this normal function. In this review we will examine the role of the AhR in the regulation of genes and proteins involved in cell adhesion and matrix remodeling, and discuss the implications of these changes in development and disease. In addition, we will discuss evidence suggesting that the AhR pathway is responsive to changes in matrix composition as well as cell-cell and cell-matrix interactions. PMID:18940186

  15. Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options.

    PubMed

    Bock, Karl Walter

    2017-04-01

    Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a 'disease tolerance defence pathway'. Further characterization of physiologic AHR functions may lead to therapeutic options.

  16. Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2

    SciTech Connect

    Kubota, Akira; Stegeman, John J.; Woodin, Bruce R.; Iwanaga, Toshihiko; Harano, Ryo; Peterson, Richard E.; Hiraga, Takeo; Teraoka, Hiroki

    2011-06-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various signs of toxicity in early life stages of vertebrates through activation of the aryl hydrocarbon receptor (AHR). We previously reported a sensitive and useful endpoint of TCDD developmental toxicity in zebrafish, namely a decrease in blood flow in the dorsal midbrain, but downstream genes involved in the effect are not known. The present study addressed the role of zebrafish cytochrome P450 1C (CYP1C) genes in association with a decrease in mesencephalic vein (MsV) blood flow. The CYP1C subfamily was recently discovered in fish and includes the paralogues CYP1C1 and CYP1C2, both of which are induced via AHR2 in zebrafish embryos. We used morpholino antisense oligonucleotides (MO or morpholino) to block initiation of translation of the target genes. TCDD-induced mRNA expression of CYP1Cs and a decrease in MsV blood flow were both blocked by gene knockdown of AHR2. Gene knockdown of CYP1C1 by two different morpholinos and CYP1C2 by two different morpholinos, but not by their 5 nucleotide-mismatch controls, was effective in blocking reduced MsV blood flow caused by TCDD. The same CYP1C-MOs prevented reduction of blood flow in the MsV caused by {beta}-naphthoflavone (BNF), representing another class of AHR agonists. Whole-mount in situ hybridization revealed that mRNA expression of CYP1C1 and CYP1C2 was induced by TCDD most strongly in branchiogenic primordia and pectoral fin buds. In situ hybridization using head transverse sections showed that TCDD increased the expression of both CYP1Cs in endothelial cells of blood vessels, including the MsV. These results indicate a potential role of CYP1C1 and CYP1C2 in the local circulation failure induced by AHR2 activation in the dorsal midbrain of the zebrafish embryo. - Research Highlights: > We examine the roles of zebrafish CYP1C1 and CYP1C2 in TCDD developmental toxicity. > TCDD induces mRNA expression of both CYP1Cs in the mesencephalic vein. > Knockdown of each

  17. Assessment of energetic costs of AhR activation by β-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis

    SciTech Connect

    Nault, Rance; Abdul-Fattah, Hiba; Mironov, Gleb G.; Berezovski, Maxim V.; Moon, Thomas W.

    2013-08-15

    Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist β-naphthoflavone (βNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesis rates, Na{sup +}/K{sup +}-ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1 μM βNF for 48 h did not alter hepatocyte AEC, protein synthesis, or Na{sup +}/K{sup +}-ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies. - Highlights: • Energetic costs of AhR activation by βNF was examined in rainbow trout hepatocytes. • Metabolic flux analysis was performed on a fish cell preparation for the first time. • Exposure to βNF led to sparing of glycogen reserves and altered enzyme activities. • Adenylate energy charge was maintained despite temporal changes in metabolism.

  18. DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells.

    PubMed

    Gaspar-Ramírez, Octavio; Pérez-Vázquez, Francisco J; Salgado-Bustamante, Mariana; González-Amaro, Roberto; Hernandez-Castro, Berenice; Pérez-Maldonado, Ivan N

    2015-01-01

    Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2',4,4',5,5'-hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 µg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-α, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression "in vitro" in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNFα induced by DDE and PCB 153 and was independent of AhR activation.

  19. The constitutively active Ah receptor (CA-Ahr) mouse as a potential model for dioxin exposure--effects in vital organs.

    PubMed

    Brunnberg, Sara; Andersson, Patrik; Lindstam, Maria; Paulson, Ivar; Poellinger, Lorenz; Hanberg, Annika

    2006-07-25

    The dioxin/aryl hydrocarbon receptor (AhR) mediates most, if not all, toxic effects of dioxins and functions as a ligand-activated transcription factor regulating transcription of a battery of genes. In order to study the mechanisms behind the toxicity of ligands of the Ah receptor we have created a transgenic mouse model expressing a constitutively active Ah receptor (CA-AhR). The mutant Ah receptor is expressed and functionally active in all organs studied. The purpose of the present study was to characterize histopathologically, the phenotype of the CA-AhR with regard to the liver, kidney, lung, heart, spleen and thymus of male and female transgenic CA-AhR mice. Moreover, cell-specific activity of the CA-AhR using up-regulation of the AhR target gene CYP1A1 as a marker, was also examined. The relative weight of liver, kidney and heart were increased while relative thymus weight was decreased. Furthermore, slight morphological lesions of the liver, kidney and spleen was seen. Expression of CYP1A1 was found in cells corresponding to endothelial cells in all of the organs studied. In some tissues additional cell types, such as hepatocytes, renal tubuli cell and Clara cells expressed CYP1A1. Both the effects on organ weights and the cellular expression of CYP1A1 in CA-AhR mice correspond well to observations in TCDD-exposed mice. In conclusion, this characterization further support that the CA-AhR mouse is a useful model for life-long continuous low-level activity of the AhR, i.e. the dioxin exposure situation of humans of the general population.

  20. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  1. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

    PubMed Central

    van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.

    2015-01-01

    Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157

  2. Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements: implications for daily intake of dioxins and PCBs.

    PubMed

    Bourdon, J A; Bazinet, T M; Arnason, T T; Kimpe, L E; Blais, J M; White, P A

    2010-11-01

    Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils derived primarily from fish are frequently consumed as supplements. Due to the tendency of persistent organic pollutants (POPs) to accumulate in exposed organisms, n-3 PUFA supplements can contain sufficient POPs to present a risk to consumers. Here we investigated PCB concentrations and aryl hydrocarbon receptor (AhR) agonist activity in 17 n-3 PUFA supplements available in Canada. PCBs ranged from <0.8 to 793 ng g(-1) oil, with salmon- and seal-derived products yielding the highest values. AhR agonist activity from a reporter gene assay ranged from 1.3 to 72.2 pg TEQ g(-1) oil, with salmon and tuna yielding the highest values. When consumed at the recommended doses and as a supplement to the average Canadian diet, seal-derived oil can contribute to exceedance of the tolerable daily intake of 20 ng PCBs kg-BW(-1)day(-1), and salmon-, tuna-, and sea herring-derived oils can contribute to exceedance of the tolerable daily intake limit of 2.3 pg TEQ kg-BW(-1)day(-1). The beneficial properties of fish and n-3 PUFA supplements, and the results of this study suggest that it is prudent to consume supplements derived from small, cold-water fatty fish. Further research will be necessary to draw firm conclusions.

  3. Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: Comparisons with AHR1-mediated reporter gene activity and in ovo toxicity

    SciTech Connect

    Manning, Gillian E.; Mundy, Lukas J.; Crump, Doug; Jones, Stephanie P.; Chiu, Suzanne; Klein, Jeff; Konstantinov, Alex; Potter, Dave; Kennedy, Sean W.

    2013-01-01

    Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species. -- Highlights: ► The chicken isn't the most sensitive species to CYP1A induction by PCB 105 and 118. ► The relative potency of PCBs differs between avian species. ► EROD activity was correlated with luciferase activity from the LRG assay. ► EROD activity was a better predictor of toxicity than CYP

  4. Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NF{kappa}B and AhR and EGFR-ERK pathway

    SciTech Connect

    Potapovich, Alla I.; Lulli, Daniela; Fidanza, Paolo; Kostyuk, Vladimir A.; De Luca, Chiara; Pastore, Saveria; Korkina, Liudmila G.

    2011-09-01

    Molecular mechanisms underlying modulation of inflammatory responses in primary human keratinocytes by plant polyphenols (PPs), namely the glycosylated phenylpropanoid verbascoside, the stilbenoid resveratrol and its glycoside polydatin, and the flavonoid quercetin and its glycoside rutin were evaluated. As non-lethal stimuli, the prototypic ligand for epidermal growth factor receptor (EGFR) transforming growth factor alpha (TGFalpha), the combination of tumor necrosis factor (TNFalpha) and interferon (IFNgamma) (T/I), UVA + UVB irradiation, and bacterial lipopolysaccharide (LPS) were used. We demonstrated differential modulation of inflammatory responses in keratinocytes at signal transduction, gene transcription, and protein synthesis levels as a function of PP chemical structure, the pro-inflammatory trigger used, and PP interaction with intracellular detoxifying systems. The PPs remarkably inhibited constitutive, LPS- and T/I-induced but not TGFalpha-induced ERK phosphorylation. They also suppressed NFkappaB activation by LPS and T/I. Verbascoside and quercetin invariably impaired EGFR phosphorylation and UV-associated aryl hydrocarbon receptor (AhR)-mediated signaling, while rutin, polydatin and resveratrol did not affect EGFR phosphorylation and further activated AhR machinery in UV-exposed keratinocytes. In general, PPs down-regulated gene expression of pro-inflammatory cytokines/enzymes, except significant up-regulation of IL-8 observed under stimulation with TGFalpha. Both spontaneous and T/I-induced release of IL-8 and IP-10 was suppressed, although 50 {mu}M resveratrol and polydatin up-regulated IL-8. At this concentration, resveratrol activated both gene expression and de novo synthesis of IL-8 and AhR-mediated mechanisms were involved. We conclude that PPs differentially modulate the inflammatory response of human keratinocytes through distinct signal transduction pathways, including AhR and EGFR. - Graphical abstract: Display Omitted Highlights

  5. Predicting the sensitivity of fishes to dioxin-like compounds: possible role of the aryl hydrocarbon receptor (AhR) ligand binding domain.

    PubMed

    Doering, Jon A; Giesy, John P; Wiseman, Steve; Hecker, Markus

    2013-03-01

    Dioxin-like compounds are chronically toxic to most vertebrates. However, dramatic differences in sensitivity to these chemicals exist both within and among vertebrate classes. A recent study found that in birds, critical amino acid residues in the aryl hydrocarbon receptor (AhR) ligand binding domain are predictive of sensitivity to dioxin-like compounds in a range of species. It is currently unclear whether similar predictive relationships exist for fishes, a group of animals at risk of exposure to dioxin-like compounds. Effects of dioxin-like compounds are mediated through the AhR in fishes and birds. However, AhR dynamics are more complex among fishes. Fishes possess AhRs that can be grouped within at least three distinct clades (AhR1, AhR2, AhR3) with each clade possibly containing multiple isoforms. AhR2 has been shown to be the active form in most teleosts, with AhR1 not binding dioxin-like compounds. The role of AhR3 in dioxin-like toxicity has not been established to date and this clade is only known to be expressed in some cartilaginous fishes. Furthermore, multiple mechanisms of sensitivity to dioxin-like compounds that are not relevant in birds could exist among fishes. Although, at this time, deficiencies exist for the development of such a predictive relationship for application to fishes, successfully establishing such relationships would offer a substantial improvement in assessment of risks of dioxin-like compounds for this class of vertebrates. Elucidation of such relationships would provide a mechanistic foundation for extrapolation among species to allow the identification of the most sensitive fishes, with the ultimate goal of the prediction of risk posed to endangered species that are not easily studied.

  6. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity

    PubMed Central

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-01-01

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity. PMID:27068235

  7. Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.

    PubMed

    Chng, Song Hui; Kundu, Parag; Dominguez-Brauer, Carmen; Teo, Wei Ling; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki; Mak, Tak Wah; Pettersson, Sven

    2016-04-12

    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity.

  8. Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds.

    PubMed

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2014-07-15

    Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachloro-dibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and 2,3,3',4,4'-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD

  9. A Dominant Negative Zebrafish Ahr2 Partially Protects Developing Zebrafish from Dioxin Toxicity

    PubMed Central

    Lanham, Kevin A.; Prasch, Amy L.; Weina, Kasia M.; Peterson, Richard E.; Heideman, Warren

    2011-01-01

    The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is thought to be caused by activation of the aryl hydrocarbon receptor (AHR). However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs). This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity. PMID:22194803

  10. Hepatic stellate cells increase the immunosuppressive function of natural Foxp3+ regulatory T cells via IDO-induced AhR activation.

    PubMed

    Kumar, Sudhir; Wang, Jiang; Thomson, Angus W; Gandhi, Chandrashekhar R

    2017-02-01

    Immunosuppressive, naturally occurring CD4(+)CD25(+)forkhead box p3(+) (Foxp3(+)) regulatory T cells (nTregs) offer potential for the treatment of immune-mediated inflammatory disorders. However, potential instability of ex vivo-expanded nTregs following their adoptive transfer may be a significant limitation. LPS-stimulated hepatic stellate cells (HSCs) induce expansion and enhance the suppressive function and stability of allogeneic nTregs We aimed to delineate mechanisms underlying HSC-induced expansion and increased potency of nTregs HSCs and nTregs were isolated from mouse livers and spleens, respectively. Following coculture with LPS-pretreated allogeneic HSCs (LPS/HSCs), proliferation of nTregs was measured by CFSE dilution, and Foxp3 expression and acetylation were determined by immunoprecipitation (IP) and Western blotting analysis. Expression of various genes associated with immunologic tolerance was determined by quantitative RT-PCR (qRT-PCR). LPS stimulation increased the expression and activity of the immunoregulatory enzyme IDO1 in HSCs, and LPS/HSCs stimulated aryl hydrocarbon receptor (AhR) signaling in cocultured nTregs Reciprocally, Tregs increased IDO1 expression in HSCs. IDO1(-/-) LPS/HSCs were inferior to WT LPS/HSCs in stimulating nTreg expansion. Pharmacologic inhibition of IDO1 in HSCs by 1-methyltryptophan (1MT) inhibited LPS/HSC-induced AhR signaling in nTregs, which was responsible for their expansion, Foxp3 expression, and stabilization of Foxp3 by increasing acetylation of lysine residues. Finally, HSCs cryopreserved, following 2-3 passages, were as potent as primary-cultured HSCs in expanding nTregs In conclusion, LPS/HSCs expand allogeneic nTregs through an IDO-dependent, AhR-mediated mechanism and increase their stability through lysine-acetylation of Foxp3. nTregs expanded by cryopreserved HSCs may have potential for clinical use.

  11. INSIGHTS FROM AHR AND ARNT GENE KNOCKOUT STUDIES REGARDING RESPONSES TO TCDD AND REGULATION OF NORMAL EMBRYONIC DEVELOPMENT

    EPA Science Inventory

    The aryl hydrocarbon receptor (AhR) and the AhR nuclear translocator (ARNT) are members of the Per-ARNT-Sim (PAS) family of proteins. The AhR binds members of the chemical family that includes dioxins, furans and coplanar polychlorinated biphenyls (PCBs). A ligand-AhR-ARNT comp...

  12. AHR-related activities in a creosote-adapted population of adult atlantic killifish, Fundulus heteroclitus, two decades post-EPA superfund status at the Atlantic Wood Site, Portsmouth, VA USA.

    PubMed

    Wojdylo, Josephine V; Vogelbein, Wolfgang; Bain, Lisa J; Rice, Charles D

    2016-08-01

    Atlantic killifish, Fundulus heteroclitus, are adapted to creosote-based PAHs at the US EPA Superfund site known as Atlantic Wood (AW) on the southern branch of the Elizabeth River, VA USA. Subsequent to the discovery of the AW population in the early 1990s, these fish were shown to be recalcitrant to CYP1A induction by PAHs under experimental conditions, and even to the time of this study, killifish embryos collected from the AW site are resistant to developmental deformities typically associated with exposure to PAHs in reference fish. Historically, however, 90 +% of the adult killifish at this site have proliferative hepatic lesions including cancer of varying severity. Several PAHs at this site are known to be ligands for the aryl hydrocarbon receptor (AHR). In this study, AHR-related activities in AW fish collected between 2011 and 2013 were re-examined nearly 2 decades after first discovery. This study shows that CYP1A mRNA expression is three-fold higher in intestines of AW killifish compared to a reference population. Using immunohistochemistry, CYP1A staining in intestines was uniformly positive compared to negative staining in reference fish. Livers of AW killifish were examined by IHC to show that CYP1A and AHR2 protein expression reflect lesions-specific patterns, probably representing differences in intrinsic cellular physiology of the spectrum of proliferative lesions comprising the hepatocarcinogenic process. We also found that COX2 mRNA expression levels were higher in AW fish livers compared to those in the reference population, suggesting a state of chronic inflammation. Overall, these findings suggest that adult AW fish are responsive to AHR signaling, and do express CYP1A and AHR2 proteins in intestines at a level above what was observed in the reference population.

  13. AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo.

    PubMed

    Wang, Xiaowen; Li, Kai; Liu, Ling; Shi, Qiong; Song, Pu; Jian, Zhe; Guo, Sen; Wang, Gang; Li, Chunying; Gao, Tianwen

    2015-09-15

    Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR -129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that -129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with -129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than -129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo.

  14. Modeling of the Aryl Hydrocarbon Receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands

    PubMed Central

    Bisson, William; Koch, Daniel; O’Donnell, Edmond; Khalil, Sammy M.; Kerkvliet, Nancy; Tanguay, Robert; Abagyan, Ruben; Kolluri, Siva Kumar

    2012-01-01

    The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor; the AhR Per-AhR/Arnt-Sim (PAS) domain binds ligands. We developed homology models of the AhR PAS domain to characterize previously observed intra- and inter-species differences in ligand binding using Molecular Docking. In silico structure-based virtual ligand screening using our model resulted in the identification of pinocembrin and 5-hydroxy-7-methoxyflavone, which promoted nuclear translocation and transcriptional activation of AhR and AhR-dependent induction of endogenous target genes. PMID:19719119

  15. Ahr function in lymphocytes: emerging concepts

    PubMed Central

    Zhou, Liang

    2015-01-01

    The aryl hydrocarbon receptor (Ahr) is an important regulator of the development and function of both innate and adaptive immune cells through roles associated with Ahr's ability to respond to cellular and dietary ligands. Recent findings have revealed tissue and context-specific functions for Ahr in both homeostasis and in during an immune response. I review these findings here, and integrate them into the current understanding of the mechanisms that regulate Ahr transcription and function. I propose a conceptual framework in which Ahr function is determined by three factors: the amount of Ahr in any given cell, the abundance and potency of Ahr ligands within certain tissues, and the tissue microenvironment wherein Ahr+ cells reside. This complexity emphasizes the necessity cell-type specific genetic approaches towards the study of Ahr function. PMID:26700314

  16. The emerging roles of AhR in physiology and immunity.

    PubMed

    Hao, Nan; Whitelaw, Murray L

    2013-09-01

    The aryl hydrocarbon receptor (AhR) is traditionally defined as a transcriptional regulator involved in adaptive xenobiotic response, however, emerging evidence supports physiological functions of AhR in normal cell development and immune response. The role of AhR in immunomodulation is multi-dimensional. On the one hand, activation of AhR by TCDD and other ligands leads to profound immunosuppression, potentially via skewed Th1/Th2 cell balance toward Th1 dominance, and boosted Treg cell differentiation. On the other hand, activation of AhR can also induce Th17 cell polarization and increase the severity of autoimmune disease. In addition to T lymphocytes, the AhR also appears to play a vital role in B cell maturation, and regulates the activity of macrophages, dendritic cells and neutrophils following lipopolysaccharide challenge or influenza virus infection. In these scenarios, activation of AhR is associated with decreased host response and reduced survival. Furthermore, gene knock out studies suggest that AhR is indispensable for the postnatal maintenance of intestinal intraepithelial lymphocytes and skin-resident dendritic epidermal gamma delta T cells, providing a potential link between AhR and gut immunity and wound healing. It is well accepted that the magnitude and the type of immune response is dependent on the local cytokine milieu and the AhR appears to be one of the key factors involved in the fine turning of this cytokine balance.

  17. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin.

    PubMed

    Hidaka, Takanori; Ogawa, Eisaku; Kobayashi, Eri H; Suzuki, Takafumi; Funayama, Ryo; Nagashima, Takeshi; Fujimura, Taku; Aiba, Setsuya; Nakayama, Keiko; Okuyama, Ryuhei; Yamamoto, Masayuki

    2017-01-01

    Atopic dermatitis is increasing worldwide in correlation with air pollution. Various organic components of pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes express constitutively active AhR and that develop atopic-dermatitis-like phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose product (the neurotrophic factor artemin) was responsible for epidermal hyper-innervation that led to hypersensitivity to pruritus. The activation of AhR via air pollutants induced expression of artemin, alloknesis, epidermal hyper-innervation and inflammation. AhR activation and ARTN expression were positively correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in keratinocytes senses environmental stimuli and elicits an atopic-dermatitis pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via activation of AhR.

  18. Dioxin-dependent and dioxin-independent gene batteries: comparison of liver and kidney in AHR-null mice.

    PubMed

    Boutros, Paul C; Bielefeld, Kirsten A; Pohjanvirta, Raimo; Harper, Patricia A

    2009-11-01

    The aryl hydrocarbon receptor (AHR) is a widely expressed ligand-dependent transcription factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Ahr-null mice are refractory to the toxic effects of dioxin exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. To address the latter issue, we defined and compared transcriptional responses to dioxin exposure in the liver and kidney of wild-type and Ahr-null adult C57BL/6J mice treated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin or corn-oil vehicle. In both tissues, essentially all effects of dioxin on hepatic mRNA levels were mediated by the AHR. Although 297 genes were altered by dioxin exposure in the liver, only 17 were changed in the kidney, including a number of well-established AHR target genes. Ahr genotype had a large effect in both tissues, profoundly remodeling both the renal and hepatic transcriptomes. Surprisingly, a large number of genes were affected by Ahr genotype in both tissues, suggesting the presence of a basal AHR gene battery. Alterations of the renal transcriptome in Ahr-null animals were associated with perturbation of specific functional pathways and enrichment of specific DNA motifs. Our results demonstrate the importance of intertissue comparisons, highlight the basal role of the AHR in liver and kidney, and support a role in development or normal physiology.

  19. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    SciTech Connect

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  20. Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells.

    PubMed

    Bermejo, Daniela A; Jackson, Shaun W; Gorosito-Serran, Melisa; Acosta-Rodriguez, Eva V; Amezcua-Vesely, Maria C; Sather, Blythe D; Singh, Akhilesh K; Khim, Socheath; Mucci, Juan; Liggitt, Denny; Campetella, Oscar; Oukka, Mohamed; Gruppi, Adriana; Rawlings, David J

    2013-05-01

    Here we identified B cells as a major source of rapid, innate-like production of interleukin 17 (IL-17) in vivo in response to infection with Trypanosoma cruzi. IL-17(+) B cells had a plasmablast phenotype, outnumbered cells of the TH17 subset of helper T cells and were required for an optimal response to this pathogen. With both mouse and human primary B cells, we found that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell-surface mucin CD45, which led to signaling dependent on the kinase Btk and production of IL-17A or IL-17F via a transcriptional program independent of the transcription factors RORγt and Ahr. Our combined data suggest that the generation of IL-17(+) B cells may be a previously unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.

  1. Alternative in vitro approach for assessing AHR-mediated CYP1A induction by dioxins in wild cormorant (Phalacrocorax carbo) population.

    PubMed

    Thuruthippallil, Leena Mol; Kubota, Akira; Kim, Eun-Young; Iwata, Hisato

    2013-06-18

    Our line of papers revealed that the common (great) cormorant (Phalacrocorax carbo) possesses two isoforms of the aryl hydrocarbon receptor (ccAHR1 and ccAHR2). This paper addresses in vitro tests of the ccAHR signaling pathways to solve two questions: (1) whether there are functional differences in the two ccAHR isoforms, and (2) whether a molecular perturbation, cytochrome P450 1A (ccCYP1A) induction, in the population-level can be predicted from the in vitro tests. The transactivation potencies mediated by ccAHR1 and ccAHR2 were measured in COS-7 cells treated with 15 selected dioxins and related compounds (DRCs), where ccAHR1 or ccAHR2 expression plasmid and ccCYP1A5 promoter/enhancer-linked luciferase reporter plasmid were transfected. For congeners that exhibited dose-dependent luciferase activities, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) relative potencies (REPs) and induction equivalency factors (IEFs) were estimated. ccAHR1-IEF profile was similar to WHO avian TCDD toxic equivalency factor (TEF) profile except for dioxin-like polychlorinated biphenyls that showed lower IEFs in ccAHR1-driven reporter assay. ccAHR2-IEF profile was different from WHO TEFs and ccAHR1-IEFs. Notably, 2,3,4,7,8-PeCDF was more potent than TCDD for ccAHR2-mediated response. Using ccAHR1- and ccAHR2-IEFs and hepatic DRC concentrations in the Lake Biwa cormorant population, total TCDD induction equivalents (IEQs) were calculated for each ccAHR-mediated response. Nonlinear regression analyses provided significant sigmoidal relationships of ccAHR1- and ccAHR2-derived IEQs with hepatic ccCYP1A5 mRNA levels, supporting the results of in vitro ccAHR-mediated TCDD dose-response curves. Collectively, our in vitro AHR reporter assay potentially could be an alternative to molecular epidemiology of the species of concern regarding CYP1A induction by AHR ligands.

  2. Tetrachlorodibenzo-p-dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR mice.

    PubMed

    Powers, B E; Lin, T-M; Vanka, A; Peterson, R E; Juraska, J M; Schantz, S L

    2005-02-01

    Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD-induced alterations in spatial learning, we tested male and female AhR-knockout (AhR-/-), heterozygous (AhR+/-) and wild-type (AhR+/+) mice on the RAM. AhR+/- male and female mice were time mated, and treated dams were dosed with 5 microg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR+/+, AhR+/- and AhR-/- mice from TCDD-exposed and unexposed litters were tested on the eight-arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD-exposed female AhR+/- mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra- and infrapyramidal mossy fiber (IIP-MF) field of the hippocampus. None of the other TCDD-exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP-MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR+/- mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.

  3. Dioxin-Dependent and Dioxin-Independent Gene Batteries: Comparison of Liver and Kidney in AHR-Null Mice

    PubMed Central

    Boutros, Paul C.; Bielefeld, Kirsten A.; Pohjanvirta, Raimo; Harper, Patricia A.

    2009-01-01

    The aryl hydrocarbon receptor (AHR) is a widely expressed ligand-dependent transcription factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Ahr-null mice are refractory to the toxic effects of dioxin exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. To address the latter issue, we defined and compared transcriptional responses to dioxin exposure in the liver and kidney of wild-type and Ahr-null adult C57BL/6J mice treated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin or corn-oil vehicle. In both tissues, essentially all effects of dioxin on hepatic mRNA levels were mediated by the AHR. Although 297 genes were altered by dioxin exposure in the liver, only 17 were changed in the kidney, including a number of well-established AHR target genes. Ahr genotype had a large effect in both tissues, profoundly remodeling both the renal and hepatic transcriptomes. Surprisingly, a large number of genes were affected by Ahr genotype in both tissues, suggesting the presence of a basal AHR gene battery. Alterations of the renal transcriptome in Ahr-null animals were associated with perturbation of specific functional pathways and enrichment of specific DNA motifs. Our results demonstrate the importance of intertissue comparisons, highlight the basal role of the AHR in liver and kidney, and support a role in development or normal physiology. PMID:19759094

  4. The bioflavonoid galangin blocks aryl hydrocarbon receptor activation and polycyclic aromatic hydrocarbon-induced pre-B cell apoptosis.

    PubMed

    Quadri, S A; Qadri, A N; Hahn, M E; Mann, K K; Sherr, D H

    2000-09-01

    Bioflavonoids are plant compounds touted for their potential to treat or prevent several diseases including cancers induced by common environmental chemicals. Much of the biologic activity of one such class of pollutants, polycyclic aromatic hydrocarbons (PAH), is mediated by the aryl hydrocarbon receptor/transcription factor (AhR). For example, the AhR regulates PAH immunotoxicity that manifests as pre-B cell apoptosis in models of B cell development. Because bioflavonoids block PAH-induced cell transformation and are structurally similar to AhR ligands, it was postulated that some of them would suppress PAH-induced, AhR-dependent immunotoxicity, possibly through a direct AhR blockade. This hypothesis was tested using a model of B cell development in which pre-B cells are cultured with and are dependent on bone marrow stromal or hepatic parenchymal cell monolayers. Of seven bioflavonoids screened, galangin (3,5,7-trihydroxyflavone) blocked PAH-induced but not C(2)-ceramide- or H(2)O(2)-induced pre-B cell apoptosis. Because galangin blocked AhR-dependent reporter gene expression, AhR complex-DNA binding, and AhR nuclear translocation, inhibition of a relatively early step in AhR signaling was implicated. This hypothesis was supported by the ability of galangin to bind the AhR and stabilize AhR-90-kDa heat shock protein complexes in the presence of AhR agonists. These studies demonstrate the utility of pre-B cell culture systems in identifying compounds capable of blocking PAH immunotoxicity, define at least one mechanism of galangin activity (i.e., repression of AhR activation), and motivate the use of this and similar dietary bioflavonoids as relatively nontoxic inhibitors of AhR agonist activity and as pharmacologic agents with which to dissect AhR signaling pathways.

  5. In vivo characterization of an AHR-dependent long non-coding RNA required for proper Sox9b expression.

    PubMed

    Garcia, Gloria R; Goodale, Britton C; Wiley, Michelle W; La Du, Jane K; Hendrix, David A; Tanguay, Robert L

    2017-04-06

    Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes. The mechanisms by which AHR2 (functional ortholog of mammalian AHR) activation leads to reduced sox9b expression levels and subsequent target organ toxicity are unknown. We have identified a novel long non-coding RNA (slincR) that is upregulated by strong AHR ligands and is located adjacent to the sox9b gene. We hypothesize that slincR is regulated by AHR2 and transcriptionally represses sox9b. The slincR transcript functions as an RNA macromolecule, and slincR expression is AHR2-dependent. Antisense knockdown of slincR results in an increase in sox9b expression during both normal development and AHR2 activation, which suggests a relief in repression. During development, slincR was expressed in tissues with sox9 essential functions, including the jaw/snout region, otic vesicle, eye, and brain. Reducing the levels of slincR resulted in altered neurological and/or locomotor behavioral responses. Our results place slincR as an intermediate between AHR2 activation and the reduction of sox9b mRNA in the AHR2 signaling pathway.

  6. Progesterone, as well as 17β-estradiol, is important for regulating AHR battery homoeostasis in the rat uterus.

    PubMed

    Rataj, Felicitas; Möller, Frank Josef; Jähne, Maria; Hönscheid, Pia; Zierau, Oliver; Vollmer, Günter; Kretzschmar, Georg

    2015-03-01

    Several studies indicate that the aryl hydrocarbon receptor (AHR), which plays an important role in mediating the toxicity of many industrial chemicals, plays an important role in the physiology of female reproductive tract organs. This makes it likely that the AHR and additional components of the AHR signalling pathway are under the control of female sex steroids. In a previous study, we could already demonstrate the regulation of many members of the AHR battery by 17β-estradiol (E2) in the uterus of rats. In this study, we addressed the potential role of progesterone (P4) in this context. In a comparative approach using ovariectomized rats which were treated for 3 days with either vehicle control, E2, progesterone (P4) or the combination of both hormones in addition to sham-operated animals, we could demonstrate that in addition to E2, P4 is also an important factor in regulating AHR signalling in the rat uterus. P4 has effects similar to E2 on uterine Ahr, Arnt and Arnt2 mRNA levels, resulting in a downregulation of these genes, while the E2-mediated downregulation of key AHR response genes Cyp1a1, Gsta2 and Ugt1 is completely antagonized by P4. As with E2, P4 leads to an increase in uterine AHR levels, especially in the endometrial epithelium despite the decrease in corresponding mRNA levels. This indicates a complex gene-specific regulatory network involving E2, P4 and possibly AHR itself to maintain all components of the AHR signalling cascade at the required levels during all stages of the oestrous cycle and pregnancy.

  7. Activation of aryl hydrocarbon receptor signaling by extracts of teak and other wood dusts.

    PubMed

    Wilson, Mark J; Sabbioni, Gabriele; Rando, Roy; Miller, Charles A

    2015-12-01

    Wood dusts, as a group, are categorized as known human carcinogens, but the risks of exposure to specific types of wood dusts and the carcinogenic chemicals they contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is linked to the carcinogenic action of specific classes of chemicals. Here we examined whether chemicals in various wood dusts had the potential to activate AhR signaling as a potential toxic mechanism of action. We found that methanol extracts of teak, walnut, mahogany, and poplar dusts contained a wide range of AhR ligand activity, whereas extracts of oak, pine, and other softwoods did not contain appreciable activity. Teak dust extract, being particularly potent, was subjected to chemical analysis. The 2-methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ potently induced AhR signaling (EC50 115 nM), confirming that this was the active ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble at bioactive concentrations in physiologically relevant fluids. The high concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic effects through activation of AhR signaling in exposed wood workers.

  8. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DNA damage in rats.

    PubMed

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies.

  9. Dose Response Data for Hormonally Active Chemicals ...

    EPA Pesticide Factsheets

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

  10. 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

  11. AIP mutations impair AhR signaling in pituitary adenoma patients fibroblasts and in GH3 cells.

    PubMed

    Lecoq, Anne-Lise; Viengchareun, Say; Hage, Mirella; Bouligand, Jérôme; Young, Jacques; Boutron, Audrey; Zizzari, Philippe; Lombès, Marc; Chanson, Philippe; Kamenický, Peter

    2016-05-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner.

  12. Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

    SciTech Connect

    Dumont, Julie Josse, Rozenn Lambert, Carine Antherieu, Sebastien Laurent, Veronique Loyer, Pascal Robin, Marie-Anne Guillouzo, Andre

    2010-11-15

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 {mu}M PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

  13. The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals

    PubMed Central

    Tian, Jijing; Feng, Yu; Fu, Hualing; Xie, Heidi Qunhui; Jiang, Joy Xiaosong; Zhao, Bin

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a highly evolutionary conserved, ligand-activated transcription factor that is best known to mediate the toxicities of dioxins and dioxin-like compounds. Phenotype of AhR-null mice, together with the recent discovery of a variety of endogenous and plant-derived ligands, point to the integral roles of AhR in normal cell physiology, in addition to its roles in sensing the environmental chemicals. Here, we summarize the current knowledge about AhR signaling pathways, its ligands and AhR-mediated effects on cell specialization, host defense and detoxification. AhR-mediated health effects particularly in liver, immune, and nervous systems, as well as in tumorgenesis are discussed. Dioxin-initiated embryotoxicity and immunosuppressive effects in fish and birds are reviewed. Recent data demonstrate that AhR is a convergence point of multiple signaling pathways that inform the cell of its external and internal environments. As such, AhR pathway is a promising potential target for therapeutics targeting nervous, liver, and autoimmune diseases through AhR ligand-mediated interventions and other perturbations of AhR signaling. Additionally, using available laboratory data obtained on animal models, AhR-centered adverse outcome pathway analysis is useful in reexamining known and potential adverse outcomes of specific or mixed compounds on wildlife. PMID:26079192

  14. Inhibition of AHR transcription by NF1C is affected by a single-nucleotide polymorphism, and is involved in suppression of human uterine endometrial cancer.

    PubMed

    Li, D; Takao, T; Tsunematsu, R; Morokuma, S; Fukushima, K; Kobayashi, H; Saito, T; Furue, M; Wake, N; Asanoma, K

    2013-10-10

    Involvement of the aryl hydrocarbon receptor (AHR) in carcinogenesis has been suggested in many studies. Upregulation of AHR has been reported in some cancer species, and an association between single-nucleotide polymorphisms (SNPs) of AHR and cancer risk or cancer development has also been reported. This evidence suggests the involvement of some specific SNPs in AHR transcriptional regulation in the process of carcinogenesis or cancer development, but there have been no studies to elucidate the mechanism involved. In this study, we identified the transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner. SNP rs10249788 was included in a consensus binding site for NF1C. Our results suggested that NF1C preferred the C allele to the T allele at rs10249788 for binding. Forced expression of NF1C suppressed the activity of the AHR promoter with C at rs10249788 stronger than that with T. Moreover, expression analysis of human uterine endometrial cancer (HEC) specimens showed greater upregulation of AHR and downregulation of NF1C than those of normal endometrium specimens. Sequence analysis showed HEC patients at advanced stages tended to possess T/T alleles more frequently than healthy women. We also demonstrated that NF1C suppressed proliferation, motility and invasion of HEC cells. This function was at least partially mediated by AHR. This study is the first to report that a polymorphism on the AHR regulatory region affected transcriptional regulation of the AHR gene in vitro. Because NF1C is a tumor suppressor, our new insights into AHR deregulation and its polymorphisms could reveal novel mechanisms of genetic susceptibility to cancer.

  15. Tissue specificity of aryl hydrocarbon receptor (AhR) mediated responses and relative sensitivity of white sturgeon (Acipenser transmontanus) to an AhR agonist.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Tendler, Brett J; Giesy, John P; Hecker, Markus

    2012-06-15

    Sturgeons are endangered in some parts of the world. Due to their benthic nature and longevity sturgeon are at greater risk of exposure to bioaccumulative contaminants such as dioxin-like compounds that are associated with sediments. Despite their endangered status, little research has been conducted to characterize the relative responsiveness of sturgeon to dioxin-like compounds. In an attempt to study the biological effects and possible associated risks of exposure to dioxin-like compounds in sturgeon, the molecular and biochemical responses of white sturgeon (Acipenser transmontanus) to a model aryl hydrocarbon receptor (AhR) agonist, β-naphthoflavone (βNF) were investigated. White sturgeon were injected intraperitoneally with one of three doses of βNF (0, 50, or 500mg/kg, bw). Rainbow trout (Oncorhynchus mykiss) were used as a reference species since their responses have been well characterized in the past. Three days following injection with βNF, fish were euthanized and livers, gills, and intestines collected for biochemical and molecular analyses. White sturgeon exposed to βNF had significantly greater ethoxyresorufin O-deethylase (EROD) activity in liver (up to 37-fold), gill (up to 41-fold), and intestine (up to 36-fold) than did unexposed controls. Rainbow trout injected with βNF exhibited EROD activity that was significantly greater in liver (88-fold), than that of controls, but was undetectable in gills or intestine. Abundance of CYP1A transcript displayed a comparable pattern of tissue-specific induction with intestine (up to 189-fold), gills (up to 53-fold), and liver (up to 21-fold). Methoxyresorufin O-deethylase (MROD) and pentoxyresorufin O-deethylase (PROD) activities were undetectable in unexposed white sturgeon tissues while exposed tissues displayed MROD activity that was only moderately greater than the activity that could be detected. Differential inducibility among liver, gill, and intestine following exposure to an AhR agonist is

  16. Current Chemical Risk Reduction Activities

    EPA Pesticide Factsheets

    EPA's existing chemicals programs address pollution prevention, risk assessment, hazard and exposure assessment and/or characterization, and risk management for chemicals substances in commercial use.

  17. Common Commercial and Consumer Products Contain Activators of the Aryl Hydrocarbon (Dioxin) Receptor

    PubMed Central

    Zhao, Bin; Bohonowych, Jessica E. S.; Timme-Laragy, Alicia; Jung, Dawoon; Affatato, Alessandra A.; Rice, Robert H.; Di Giulio, Richard T.; Denison, Michael S.

    2013-01-01

    Activation of the Ah receptor (AhR) by halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), can produce a wide variety of toxic and biological effects. While recent studies have shown that the AhR can bind and be activated by structurally diverse chemicals, how widespread of these AhR agonists are in environmental, biological and synthetic materials remains to be determined. Using AhR-based assays, we demonstrate the presence of potent AhR agonists in a variety of common commercial and consumer items. Solvent extracts of paper, rubber and plastic products contain chemicals that can bind to and stimulate AhR DNA binding and/or AhR-dependent gene expression in hepatic cytosol, cultured cell lines, human epidermis and zebrafish embryos. In contrast to TCDD and other persistent dioxin-like HAHs, activation of AhR-dependent gene expression by these extracts was transient, suggesting that the agonists are metabolically labile. Solvent extracts of rubber products produce AhR-dependent developmental toxicity in zebrafish in vivo, and inhibition of expression of the metabolic enzyme CYP1A, significantly increased their toxic potency. Although the identity of the responsible AhR-active chemicals and their toxicological impact remain to be determined, our data demonstrate that AhR active chemicals are widely distributed in everyday products. PMID:23441220

  18. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region

    PubMed Central

    Englert, Neal A.; Turesky, Robert J.; Han, Weiguo; Bessette, Erin E.; Spivack, Simon D.; Caggana, Michele; Spink, David C.; Spink, Barbara C.

    2014-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)n repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)n was n = 4>5≫6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis. PMID:22728919

  19. Genetic and epigenetic regulation of AHR gene expression in MCF-7 breast cancer cells: role of the proximal promoter GC-rich region.

    PubMed

    Englert, Neal A; Turesky, Robert J; Han, Weiguo; Bessette, Erin E; Spivack, Simon D; Caggana, Michele; Spink, David C; Spink, Barbara C

    2012-09-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, contributes to carcinogenesis through its role in the regulation of cytochrome P450 1 (CYP1)-catalyzed metabolism of carcinogens. Here, we investigated genetic and epigenetic mechanisms that affect AhR expression. Analyses of the human AHR proximal promoter in MCF-7 human breast cancer cells using luciferase assays and electrophoretic mobility shift assays revealed multiple specificity protein (Sp) 1 binding sequences that are transcriptional activators in vitro. The regulation of AhR expression was evaluated in long-term estrogen exposed (LTEE) MCF-7 cells, which showed increased AhR expression, enhanced CYP1 inducibility, and increased capacity to form DNA adducts when exposed to the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. The increased AhR expression in LTEE cells was found not to result from increased mRNA stability, differential RNA processing, or decreased DNA methylation. Analysis of the AHR proximal promoter region using chromatin immunoprecipitation confirmed that enhanced expression of AhR in LTEE cells involves changes in histone modifications, notably decreased trimethylation of histone 3, lysine 27. Upon further examination of the GC-rich Sp1-binding region, we confirmed that it contains a polymorphic (GGGGC)(n) repeat. In a population of newborns from New York State, the allele frequency of (GGGGC)(n) was n = 4 > 5 ≫ 6, 2. Circular dichroism spectroscopy revealed the ability of sequences of this GC-rich region to form guanine-quadruplex structures in vitro. These studies revealed multiple levels at which AhR expression may be controlled, and offer additional insights into mechanisms regulating AhR expression that can ultimately impact carcinogenesis.

  20. Intersection of AHR and Wnt Signaling in Development, Health, and Disease

    PubMed Central

    Schneider, Andrew J.; Branam, Amanda M.; Peterson, Richard E.

    2014-01-01

    The AHR (aryl hydrocarbon receptor) and Wnt (wingless-related MMTV integration site) signaling pathways have been conserved throughout evolution. Appropriately regulated signaling through each pathway is necessary for normal development and health, while dysregulation can lead to developmental defects and disease. Though both pathways have been vigorously studied, there is relatively little research exploring the possibility of crosstalk between these pathways. In this review, we provide a brief background on (1) the roles of both AHR and Wnt signaling in development and disease, and (2) the molecular mechanisms that characterize activation of each pathway. We also discuss the need for careful and complete experimental evaluation of each pathway and describe existing research that explores the intersection of AHR and Wnt signaling. Lastly, to illustrate in detail the intersection of AHR and Wnt signaling, we summarize our recent findings which show that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced disruption of Wnt signaling impairs fetal prostate development. PMID:25286307

  1. The Role of AhR in Autoimmune Regulation and Its Potential as a Therapeutic Target against CD4 T Cell Mediated Inflammatory Disorder

    PubMed Central

    Zhu, Conghui; Xie, Qunhui; Zhao, Bin

    2014-01-01

    AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently. PMID:24905409

  2. The role of AhR in autoimmune regulation and its potential as a therapeutic target against CD4 T cell mediated inflammatory disorder.

    PubMed

    Zhu, Conghui; Xie, Qunhui; Zhao, Bin

    2014-06-05

    AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.

  3. Genome Editing of the CYP1A1 Locus in iPSCs as a Platform to Map AHR Expression throughout Human Development

    PubMed Central

    Smith, Brenden W.; Stanford, Elizabeth A.; Sherr, David H.; Murphy, George J.

    2016-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that increases the expression of detoxifying enzymes upon ligand stimulation. Recent studies now suggest that novel endogenous roles of the AHR exist throughout development. In an effort to create an optimized model system for the study of AHR signaling in several cellular lineages, we have employed a CRISPR/CAS9 genome editing strategy in induced pluripotent stem cells (iPSCs) to incorporate a reporter cassette at the transcription start site of one of its canonical targets, cytochrome P450 1A1 (CYP1A1). This cell line faithfully reports on CYP1A1 expression, with luciferase levels as its functional readout, when treated with an endogenous AHR ligand (FICZ) at escalating doses. iPSC-derived fibroblast-like cells respond to acute exposure to environmental and endogenous AHR ligands, and iPSC-derived hepatocytes increase CYP1A1 in a similar manner to primary hepatocytes. This cell line is an important innovation that can be used to map AHR activity in discrete cellular subsets throughout developmental ontogeny. As further endogenous ligands are proposed, this line can be used to screen for safety and efficacy and can report on the ability of small molecules to regulate critical cellular processes by modulating the activity of the AHR. PMID:27148368

  4. AHR2 morpholino knockdown reduces the toxicity of total particulate matter to zebrafish embryos.

    PubMed

    Massarsky, Andrey; Bone, Audrey J; Dong, Wu; Hinton, David E; Prasad, G L; Di Giulio, Richard T

    2016-10-15

    The zebrafish embryo has been proposed as a 'bridge model' to study the effects of cigarette smoke on early development. Previous studies showed that exposure to total particulate matter (TPM) led to adverse effects in developing zebrafish, and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways play important roles. This study investigated the roles of these two pathways in mediating TPM toxicity. The study consisted of four experiments. In experiment I, zebrafish embryos were exposed from 6h post fertilization (hpf) until 96hpf to TPM0.5 and TPM1.0 (corresponding to 0.5 and 1.0μg/mL equi-nicotine units) in the presence or absence of an antioxidant (N-acetyl cysteine/NAC) or a pro-oxidant (buthionine sulfoximine/BSO). In experiment II, TPM exposures were performed in embryos that were microinjected with nuclear factor erythroid 2-related factor 2 (Nrf2), AHR2, cytochrome P450 1A (CYP1A), or CYP1B1 morpholinos, and deformities were assessed. In experiment III, embryos were exposed to TPM, and embryos/larvae were collected at 24, 48, 72, and 96hpf to assess several genes associated with the antioxidant and AHR pathways. Lastly, experiment IV assessed the activity and protein levels of CYP1A and CYP1B1 after exposure to TPM. We demonstrate that the incidence of TPM-induced deformities was generally not affected by NAC/BSO treatments or Nrf2 knockdown. In contrast, AHR2 knockdown reduced, while CYP1A or CYP1B1 knockdowns elevated the incidence of some deformities. Moreover, as shown by gene expression the AHR pathway, but not the antioxidant pathway, was induced in response to TPM exposure, providing further evidence for its importance in mediating TPM toxicity.

  5. Inorganic chemically active adsorbents (ICAAs)

    SciTech Connect

    Ally, M.R.; Tavlarides, L.

    1997-10-01

    Oak Ridge National Laboratory (ORNL) researchers are developing a technology that combines metal chelation extraction technology and synthesis chemistry. They begin with a ceramic substrate such as alumina, titanium oxide or silica gel because they provide high surface area, high mechanical strength, and radiolytic stability. One preparation method involves silylation to hydrophobize the surface, followed by chemisorption of a suitable chelation agent using vapor deposition. Another route attaches newly designed chelating agents through covalent bonding by the use of coupling agents. These approaches provide stable and selective, inorganic chemically active adsorbents (ICAAs) tailored for removal of metals. The technology has the following advantages over ion exchange: (1) higher mechanical strength, (2) higher resistance to radiation fields, (3) higher selectivity for the desired metal ion, (4) no cation exchange, (5) reduced or no interference from accompanying anions, (6) faster kinetics, and (7) easy and selective regeneration. Target waste streams include metal-containing groundwater/process wastewater at ORNL`s Y-12 Plant (multiple metals), Savannah River Site (SRS), Rocky Flats (multiple metals), and Hanford; aqueous mixed wastes at Idaho National Engineering Laboratory (INEL); and scrubber water generated at SRS and INEL. Focus Areas that will benefit from this research include Mixed Waste, and Subsurface Contaminants.

  6. The Nuclear Receptor AhR Controls Bone Homeostasis by Regulating Osteoclast Differentiation via the RANK/c-Fos Signaling Axis

    PubMed Central

    Izawa, Takashi; Arakaki, Rieko; Mori, Hiroki; Tsunematsu, Takaaki; Kudo, Yasusei; Tanaka, Eiji

    2016-01-01

    The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)–mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow–derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, bone marrow macrophages isolated from AhR−/− mice exhibited impaired phosphorylation of Akt and MAPK as well as NF-κB, whereas their response to M-CSF remained unchanged. Osteoclast differentiation mediated by the AhR signaling pathway was also regulated in an RANKL/c-Fos–dependent manner. Furthermore, ligand activation of AhR by the smoke toxin benzo[a]pyrene accelerated osteoclast differentiation in a receptor-dependent manner, and AhR-dependent regulation of mitochondrial biogenesis in osteoclasts was observed. Moreover, AhR−/− mice exhibited impaired bone healing with delayed endochondral ossification. Taken together, the present results suggest that the RANKL/AhR/c-Fos signaling axis plays a critical role in osteoclastogenesis, thereby identifying the potential of AhR in treating pathological, inflammatory, or metabolic disorders of the bone. PMID:27849171

  7. Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice

    PubMed Central

    Zhang, Limin; Hatzakis, Emmanuel; Nichols, Robert G.; Hao, Ruixin; Correll, Jared; Smith, Philip B.; Chiaro, Christopher R.; Perdew, Gary H.; Patterson, Andrew D.

    2016-01-01

    Environmental exposure to dioxins and dioxin-like compounds poses a significant health risk for human health. Developing a better understanding of the mechanisms of toxicity through activation of the aryl hydrocarbon receptor (AHR) is likely to improve the reliability of risk assessment. In this study, the AHR-dependent metabolic response of mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF) were assessed using global 1H nuclear magnetic resonance (NMR)-based metabolomics and targeted metabolic profiling of extracts obtained from serum and liver. 1H NMR analyses revealed that TCDF exposure suppressed gluconeogenesis and glycogenolysis, stimulated lipogenesis, and triggered inflammatory gene expression in an Ahr-dependent manner. Targeted analyses using gas chromatography mass spectrometry showed TCDF treatment altered the ratio of unsaturated/saturated fatty acids. Consistent with this observation, an increase in hepatic expression of stearoyl coenzyme A desaturase 1 was also observed. In addition, TCDF exposure resulted in inhibition of de novo fatty acid biosynthesis manifested by down-regulation of acetyl-CoA, malonyl-CoA and palmitoyl-CoA metabolites and related mRNA levels. In contrast, no significant changes in the levels of glucose and lipid were observed in serum and liver obtained from Ahr-null mice following TCDF treatment, thus strongly supporting the important role of the AHR in mediating the metabolic effects seen following TCDF exposure. PMID:26023891

  8. Simulator for SUPO, a Benchmark Aqueous Homogeneous Reactor (AHR)

    SciTech Connect

    Klein, Steven Karl; Determan, John C.

    2015-10-14

    A simulator has been developed for SUPO (Super Power) an aqueous homogeneous reactor (AHR) that operated at Los Alamos National Laboratory (LANL) from 1951 to 1974. During that period SUPO accumulated approximately 600,000 kWh of operation. It is considered the benchmark for steady-state operation of an AHR. The SUPO simulator was developed using the process that resulted in a simulator for an accelerator-driven subcritical system, which has been previously reported.

  9. The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells.

    PubMed

    Baricza, Eszter; Tamási, Viola; Marton, Nikolett; Buzás, Edit I; Nagy, György

    2016-01-01

    The aryl hydrocarbon receptor (AHR) is a cytoplasmic transcription factor, which plays an essential role in the xenobiotic metabolism in a wide variety of cells. The AHR gene is evolutionarily conserved and it has a central role not only in the differentiation and maturation of many tissues, but also in the toxicological metabolism of the cell by the activation of metabolizing enzymes. Several lines of evidence support that both AHR agonists and antagonists have profound immunological effects; and recently, the AHR has been implicated in antibacterial host defense. According to recent studies, the AHR is essential for the differentiation and activation of T helper 17 (Th17) cells. It is well known that Th17 cells have a central role in the development of inflammation, which is crucial in the defense against pathogens. In addition, Th17 cells play a major role in the pathogenesis of several autoimmune diseases such as rheumatoid arthritis. Therefore, the AHR may provide connection between the environmental chemicals, the immune regulation, and autoimmunity. In the present review, we summarize the role of the AHR in the Th17 cell functions.

  10. Molecular Determinants of Species-Specific Agonist and Antagonist Activity of A Substituted Flavone towards the Aryl Hydrocarbon Receptor*

    PubMed Central

    Henry, E. C.; Gasiewicz, T. A.

    2008-01-01

    The aryl hydrocarbon receptor (AhR) mediates the toxicity of dioxins and related xenobiotics. Other chemicals also bind the AhR to elicit either agonist or antagonist responses. Here we used site-directed mutagenesis within the ligand binding domain of murine AhR to probe for specific residues that might interact differentially with the antagonist 3’-methoxy-4’-nitroflavone (MNF) compared with the prototypical agonist TCDD. Reduced 3 H-TCDD binding, dioxin-response element (DRE) binding, and transcriptional activity were observed for several point mutants. One mutation, R355I, changed the response to MNF from antagonist to agonist. Notably, Ile is the residue found in the guinea pig AhR, towards which MNF has partial agonist activity in contrast to its strong antagonist activity in mouse. A similar reversal of response to MNF was observed in chimeric AhRs in which the C-terminal region of mAhR was replaced with the guinea pig C-terminal region. These data demonstrate that different amino acids can be important in binding of different AhR ligands and can mediate distinct responses. The ultimate response of the AhR also depends on how other portions of the receptor protein are functionally coupled to the initial ligand binding event. PMID:18294953

  11. Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop

    PubMed Central

    Effner, Renate; Hiller, Julia; Eyerich, Stefanie; Traidl-Hoffmann, Claudia; Brockow, Knut; Triggiani, Massimo; Behrendt, Heidrun; Schmidt-Weber, Carsten B.; Buters, Jeroen T. M.

    2017-01-01

    The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods. CYP1 inhibition increased the expression levels of the stem cell factor receptor (c-Kit) and interleukin (IL)-22 but decreased IL-17. Single cell analyses showed that CYP1 inhibition especially promoted CD4+ helper T (Th) cells that co-express c-Kit and IL-22 simultaneously. The addition of an AHR antagonist reversed all these effects. In addition to T cells, we screened other human immune cells for CYP and found cell-specific fingerprints, suggesting that similar mechanisms are present in multiple immune cells. We describe a feedback loop yet unknown in human immune cells where CYP1 inhibition resulted in an altered AHR-dependent immune response. This mechanism relates CYP1-dependent metabolism of environmental small molecules to human immunity. PMID:28276465

  12. Deletion of Aryl Hydrocarbon Receptor AHR in Mice Leads to Subretinal Accumulation of Microglia and RPE Atrophy

    PubMed Central

    Kim, Soo-Young; Yang, Hyun-Jin; Chang, Yi-Sheng; Kim, Jung-Woong; Brooks, Matthew; Chew, Emily Y.; Wong, Wai T.; Fariss, Robert N.; Rachel, Rivka A.; Cogliati, Tiziana; Qian, Haohua; Swaroop, Anand

    2014-01-01

    Purpose. The aryl hydrocarbon receptor (AHR) is a ligand-activated nuclear receptor that regulates cellular response to environmental signals, including UV and blue wavelength light. This study was undertaken to elucidate AHR function in retinal homeostasis. Methods. RNA-seq data sets were examined for Ahr expression in the mouse retina and rod photoreceptors. The Ahr−/− mice were evaluated by fundus imaging, optical coherence tomography, histology, immunohistochemistry, and ERG. For light damage experiments, adult mice were exposed to 14,000 to 15,000 lux of diffuse white light for 2 hours. Results. In mouse retina, Ahr transcripts were upregulated during development, with continued increase in aging rod photoreceptors. Fundus examination of 3-month-old Ahr−/− mice revealed subretinal autofluorescent spots, which increased in number with age and following acute light exposure. Ahr−/− retina also showed subretinal microglia accumulation that correlated with autofluorescence changes, RPE abnormalities, and reactivity against immunoglobulin, complement factor H, and glial fibrillary acidic protein. Functionally, Ahr−/− mice displayed reduced ERG c-wave amplitudes. Conclusions. The Ahr−/− mice exhibited subretinal accumulation of microglia and focal RPE atrophy, phenotypes observed in AMD. Together with a recently published report on another Ahr−/− mouse model, our study suggests that AHR has a protective role in the retina as an environmental stress sensor. As such, its altered function may contribute to human AMD progression and provide a target for pharmacological intervention. PMID:25159211

  13. Role of DNA methylation of AHR1 and AHR2 promoters in differential sensitivity to PCBs in Atlantic Killifish, Fundulus heteroclitus.

    PubMed

    Aluru, Neelakanteswar; Karchner, Sibel I; Hahn, Mark E

    2011-01-17

    Atlantic killifish (Fundulus heteroclitus) inhabiting the PCB-contaminated Superfund site in New Bedford Harbor (MA, USA) have evolved genetic resistance to the toxic effects of these compounds. They also lack induction of cytochrome P4501A (CYP1A) and other aryl hydrocarbon receptor (AHR)-dependent responses after exposure to AHR agonists, suggesting an overall down-regulation of the AHR signaling pathway. In this study, we hypothesized that the genetic resistance is due to altered AHR expression resulting from hypermethylation of DNA in the promoter region of AHR genes in fish inhabiting New Bedford Harbor. To test this hypothesis, we cloned and sequenced AHR1 and AHR2 promoter regions and employed bisulfite conversion-polymerase chain reaction (BS-PCR) followed by clonal analysis to compare the methylation status of CpG islands of AHR1 and AHR2 in livers of adult killifish collected from New Bedford Harbor and a reference site (Scorton Creek, MA). No significant differences in methylation profiles were observed in either AHR1 or AHR2 promoter regions between NBH and SC fish. However, hypermethylation of the AHR1 promoter correlated with low expression of transcripts in the liver in both populations. In comparison to AHR1, hepatic mRNA expression of AHR2 is high and its promoter is hypomethylated. Taken together, our results suggest that genetic resistance to contaminants in NBH fish is not due to altered methylation of AHR promoter regions, but that promoter methylation may control tissue-specific expression of AHR genes in killifish.

  14. Mono-Substituted Isopropylated Triaryl Phosphate, a Major Component of Firemaster 550, is an AHR Agonist that Exhibits AHR-Independent Cardiotoxicity in Zebrafish

    PubMed Central

    Gerlach, Cory V.; Das, Siba R.; Volz, David C.; Bisson, William H.; Kolluri, Siva K.; Tanguay, Robert L.

    2014-01-01

    Firemaster 550 (FM550) is an additive flame retardant mixture used within polyurethane foam and is increasingly found in house dust and the environment due to leaching. Despite the widespread use of FM550, very few studies have investigated the potential toxicity of its ingredients during early vertebrate development. In the current study, we sought to specifically investigate mono-substituted isopropylated triaryl phosphate (mITP), a component comprising approximately 32% of FM550, which has been shown to cause cardiotoxicity during zebrafish embryogenesis. Previous research showed that developmental defects are rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191), suggesting that mITP-induced toxicity was AHR-dependent. As zebrafish have three known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A-and AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP-induced cardiotoxicity. As in silico structural homology modeling predicted that mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR involvement in vivo by measuring CYP1A mRNA and protein expression following exposure to mITP in the presence or absence of CH223191 or AHR-specific morpholinos. Based on these studies, we found that mITP interacts with both AHR2 and AHR1B isoforms to induce CYP1A expression. However, while CH223191 blocked mITP-induced CYP1A induction and cardiotoxicity, knockdown of all three AHR isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable CYP1A induction. Overall, these results suggest that, while mITP is an AHR agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191. PMID:24865613

  15. Mono-substituted isopropylated triaryl phosphate, a major component of Firemaster 550, is an AHR agonist that exhibits AHR-independent cardiotoxicity in zebrafish.

    PubMed

    Gerlach, Cory V; Das, Siba R; Volz, David C; Bisson, William H; Kolluri, Siva K; Tanguay, Robert L

    2014-09-01

    Firemaster 550 (FM550) is an additive flame retardant mixture used within polyurethane foam and is increasingly found in house dust and the environment due to leaching. Despite the widespread use of FM550, very few studies have investigated the potential toxicity of its ingredients during early vertebrate development. In the current study, we sought to specifically investigate mono-substituted isopropylated triaryl phosphate (mITP), a component comprising approximately 32% of FM550, which has been shown to cause cardiotoxicity during zebrafish embryogenesis. Previous research showed that developmental defects are rescued using an aryl hydrocarbon receptor (AHR) antagonist (CH223191), suggesting that mITP-induced toxicity was AHR-dependent. As zebrafish have three known AHR isoforms, we used a functional AHR2 knockout line along with AHR1A- and AHR1B-specific morpholinos to determine which AHR isoform, if any, mediates mITP-induced cardiotoxicity. As in silico structural homology modeling predicted that mITP may bind favorably to both AHR2 and AHR1B isoforms, we evaluated AHR involvement in vivo by measuring CYP1A mRNA and protein expression following exposure to mITP in the presence or absence of CH223191 or AHR-specific morpholinos. Based on these studies, we found that mITP interacts with both AHR2 and AHR1B isoforms to induce CYP1A expression. However, while CH223191 blocked mITP-induced CYP1A induction and cardiotoxicity, knockdown of all three AHR isoforms failed to block mITP-induced cardiotoxicity in the absence of detectable CYP1A induction. Overall, these results suggest that, while mITP is an AHR agonist, mITP causes AHR-independent cardiotoxicity through a pathway that is also antagonized by CH223191.

  16. Science Activities in Energy: Chemical Energy.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 15 activities relating to chemical energy. Activities are simple, concrete experiments for fourth, fifth and sixth grades which illustrate principles and problems relating to energy. Each activity is outlined on a single card which is introduced by a question. A teacher's…

  17. Chemical Potentials and Activities: An Electrochemical Introduction.

    ERIC Educational Resources Information Center

    Wetzel, T. L.; And Others

    1986-01-01

    Describes a laboratory experiment which explores the effects of adding inert salts to electrolytic cells and demonstrates the difference between concentration and chemical activity. Examines chemical potentials as the driving force of reactions. Provides five examples of cell potential and concentration change. (JM)

  18. Zebrafish Cardiotoxicity: The Effects of CYP1A Inhibition and AHR2 Knockdown Following Exposure to Weak Aryl Hydrocarbon Receptor Agonists

    PubMed Central

    Clark, Bryan William; Van Tiem Garner, Lindsey; Di Giulio, Richard Thomas

    2014-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates many of the toxic effects of dioxin-like compounds (DLCs) and some polycyclic aromatic hydrocarbons (PAHs). Strong AHR agonists, such as certain polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause severe cardiac teratogenesis in fish embryos. Moderately strong AHR agonists, such as benzo[a]pyrene and β-naphthoflavone, have been shown to cause similar cardiotoxic effects when coupled with a cytochrome P450 1A (CYP1A) inhibitor, such as fluoranthene (FL). We sought to determine if weak AHR agonists, when combined with a CYP1A inhibitor (FL) or CYP1A morpholino gene knockdown, are capable of causing cardiac deformities similar to moderately strong AHR agonists (Wassenberg and Di Giulio 2004; Wassenberg and Di Giulio 2004; Billiard, Timme-Laragy et al. 2006; Van Tiem and Di Giulio 2011). The weak AHR agonists included the following: carbaryl, phenanthrene, 2-methylindole, 3-methylindole, indigo, and indirubin. The results showed a complex pattern of cardiotoxic response to weak agonist inhibitor exposure and morpholino-knockdown. Danio rerio (zebrafish) embryos were first exposed to weak AHR agonists at equimolar concentrations. The agonists were assessed for their relative potency as inducers of CYP1 enzyme activity, measured by the ethoxyresorufin-o-deethylase (EROD) assay, and cardiac deformities. Carbaryl, 2-methylindole, and 3-methylindole induced the highest CYP1A activity in zebrafish. Experiments were then conducted to determine the individual cardiotoxicity of each compound. Next, zebrafish were co-exposed to each agonist (at concentrations below those determined to be cardiotoxic) and FL in combination to assess if CYP1A inhibition could induce cardiac deformities. Carbaryl, 2-methylindole, 3-methylindole, and phenanthrene significantly increased pericardial edema relative to controls when combined with FL. To further evaluate the

  19. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

    SciTech Connect

    Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K. . E-mail: mkwalker@unm.edu

    2006-04-15

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET{sub A} receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, {beta}-myosin heavy chain ({beta}-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET{sub A} receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and {beta}-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET{sub A} receptor as primary determinants of hypertension and cardiac pathology in AhR null mice.

  20. A novel AhR ligand, 2AI, protects the retina from environmental stress

    PubMed Central

    Gutierrez, Mark A.; Davis, Sonnet S.; Rosko, Andrew; Nguyen, Steven M.; Mitchell, Kylie P.; Mateen, Samiha; Neves, Joana; Garcia, Thelma Y.; Mooney, Shaun; Perdew, Gary H.; Hubbard, Troy D.; Lamba, Deepak A.; Ramanathan, Arvind

    2016-01-01

    Various retinal degenerative diseases including dry and neovascular age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy are associated with the degeneration of the retinal pigmented epithelial (RPE) layer of the retina. This consequently results in the death of rod and cone photoreceptors that they support, structurally and functionally leading to legal or complete blindness. Therefore, developing therapeutic strategies to preserve cellular homeostasis in the RPE would be a favorable asset in the clinic. The aryl hydrocarbon receptor (AhR) is a conserved, environmental ligand-dependent, per ARNT-sim (PAS) domain containing bHLH transcription factor that mediates adaptive response to stress via its downstream transcriptional targets. Using in silico, in vitro and in vivo assays, we identified 2,2′-aminophenyl indole (2AI) as a potent synthetic ligand of AhR that protects RPE cells in vitro from lipid peroxidation cytotoxicity mediated by 4-hydroxynonenal (4HNE) as well as the retina in vivo from light-damage. Additionally, metabolic characterization of this molecule by LC-MS suggests that 2AI alters the lipid metabolism of RPE cells, enhancing the intracellular levels of palmitoleic acid. Finally, we show that, as a downstream effector of 2AI-mediated AhR activation, palmitoleic acid protects RPE cells from 4HNE-mediated stress, and light mediated retinal degeneration in mice. PMID:27364765

  1. Self-diffusiophoresis of chemically active colloids

    NASA Astrophysics Data System (ADS)

    Popescu, Mihail N.; Uspal, William E.; Dietrich, Siegfried

    2016-11-01

    Chemically active colloids locally change the chemical composition of their solvent via catalytic reactions which occur on parts of their surface. They achieve motility by converting the released chemical free energy into mechanical work through various mechanisms, such as phoresis. Here we discuss the theoretical aspects of self-diffusiophoresis, which - despite being one of the simplest motility mechanisms - captures many of the general features characterizing self-phoresis, such as self-generated and maintained hydrodynamic flows "driven" by surface activity induced inhomogeneities in solution. By studying simple examples, which provide physical insight, we highlight the complex phenomenology which can emerge from self-diffusiophoresis.

  2. Metabolic activation and inactivation of chemical carcinogens

    SciTech Connect

    Pelkonen, O.; Vaehaekangas, K.

    1980-09-01

    Chemical carcinogens are metabolized by numerous pathways catalyzed by enzymes in endoplasmic reticulum and other parts of the cell. Reactions in which functional groups are created are especially important in the activation of polycyclic hydrocarbon carcinogens to ultimate carcinogenic forms, although other enzymes may also participate in the activation of other chemical carcinogens. The reasons why carcinogens act on specific target tissues are incompletely understood, although differences in enzyme profiles between tissues certainly contribute to the target tissue variability. The concept of metabolic activation of carcinogens by body's own enzymes has led to the development of short-term assay systems, which essentially measure the production of biologically active metabolites from potential carcinogens.

  3. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    PubMed Central

    2011-01-01

    Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485

  4. The Chemical Composition of the Active Stars

    NASA Astrophysics Data System (ADS)

    Glazunova, L. V.

    The comparison of the results of the studies of the active stars' chemical composition obtained by different authors has been performed. It was concluded that the difference between the abundances of some elements in active and inactive stars becomes significant (> 3σ) only for the active stars with high chromospheric activity (lgR'HK > -4). This is the case primarily for the light elements, namely Li, Na and Al, as well as heavy elements with Z > 30.

  5. Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium

    PubMed Central

    Oshida, Keiyu; Vasani, Naresh; Jones, Carlton; Moore, Tanya; Hester, Susan; Nesnow, Stephen; Auerbach, Scott; Geter, David R.; Aleksunes, Lauren M.; Thomas, Russell S.; Applegate, Dawn; Klaassen, Curtis D.; Corton, J. Christopher

    2015-01-01

    The nuclear receptor family member constitutive activated receptor (CAR) is activated by structurally diverse drugs and environmentally-relevant chemicals leading to transcriptional regulation of genes involved in xenobiotic metabolism and transport. Chronic activation of CAR increases liver cancer incidence in rodents, whereas suppression of CAR can lead to steatosis and insulin insensitivity. Here, analytical methods were developed to screen for chemical treatments in a gene expression compendium that lead to alteration of CAR activity. A gene expression biomarker signature of 83 CAR-dependent genes was identified using microarray profiles from the livers of wild-type and CAR-null mice after exposure to three structurally-diverse CAR activators (CITCO, phenobarbital, TCPOBOP). A rank-based algorithm (Running Fisher’s algorithm (p-value ≤ 10-4)) was used to evaluate the similarity between the CAR biomarker signature and a test set of 28 and 32 comparisons positive or negative, respectively, for CAR activation; the test resulted in a balanced accuracy of 97%. The biomarker signature was used to identify chemicals that activate or suppress CAR in an annotated mouse liver/primary hepatocyte gene expression database of ~1850 comparisons. CAR was activated by 1) activators of the aryl hydrocarbon receptor (AhR) in wild-type but not AhR-null mice, 2) pregnane X receptor (PXR) activators in wild-type and to lesser extents in PXR-null mice, and 3) activators of PPARα in wild-type and PPARα-null mice. CAR was consistently activated by five conazole fungicides and four perfluorinated compounds. Comparison of effects in wild-type and CAR-null mice showed that the fungicide propiconazole increased liver weight and hepatocyte proliferation in a CAR-dependent manner, whereas the perfluorinated compound perfluorooctanoic acid (PFOA) increased these endpoints in a CAR-independent manner. A number of compounds suppressed CAR coincident with increases in markers of

  6. Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium.

    PubMed

    Oshida, Keiyu; Vasani, Naresh; Jones, Carlton; Moore, Tanya; Hester, Susan; Nesnow, Stephen; Auerbach, Scott; Geter, David R; Aleksunes, Lauren M; Thomas, Russell S; Applegate, Dawn; Klaassen, Curtis D; Corton, J Christopher

    2015-01-01

    The nuclear receptor family member constitutive activated receptor (CAR) is activated by structurally diverse drugs and environmentally-relevant chemicals leading to transcriptional regulation of genes involved in xenobiotic metabolism and transport. Chronic activation of CAR increases liver cancer incidence in rodents, whereas suppression of CAR can lead to steatosis and insulin insensitivity. Here, analytical methods were developed to screen for chemical treatments in a gene expression compendium that lead to alteration of CAR activity. A gene expression biomarker signature of 83 CAR-dependent genes was identified using microarray profiles from the livers of wild-type and CAR-null mice after exposure to three structurally-diverse CAR activators (CITCO, phenobarbital, TCPOBOP). A rank-based algorithm (Running Fisher's algorithm (p-value ≤ 10(-4))) was used to evaluate the similarity between the CAR biomarker signature and a test set of 28 and 32 comparisons positive or negative, respectively, for CAR activation; the test resulted in a balanced accuracy of 97%. The biomarker signature was used to identify chemicals that activate or suppress CAR in an annotated mouse liver/primary hepatocyte gene expression database of ~1850 comparisons. CAR was activated by 1) activators of the aryl hydrocarbon receptor (AhR) in wild-type but not AhR-null mice, 2) pregnane X receptor (PXR) activators in wild-type and to lesser extents in PXR-null mice, and 3) activators of PPARα in wild-type and PPARα-null mice. CAR was consistently activated by five conazole fungicides and four perfluorinated compounds. Comparison of effects in wild-type and CAR-null mice showed that the fungicide propiconazole increased liver weight and hepatocyte proliferation in a CAR-dependent manner, whereas the perfluorinated compound perfluorooctanoic acid (PFOA) increased these endpoints in a CAR-independent manner. A number of compounds suppressed CAR coincident with increases in markers of

  7. Green fluorescent protein (GFP) as a marker of aryl hydrocarbon receptor (AhR) function in developing zebrafish (Danio rerio).

    PubMed

    Mattingly, C J; McLachlan, J A; Toscano, W A

    2001-08-01

    We developed an inducible in vivo reporter system to examine expression of the aryl hydrocarbon receptor (AhR) during development in zebrafish (Danio rerio). AhR is a ligand-activated transcription factor that mediates the toxic actions of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Induction of cytochrome P4501A1 (CYP1A1) is an early biomarker of AhR activation. A 1905 base pair region of the human CYP1A1 promoter/enhancer region was regulated by AhR in zebrafish liver cells after exposure to TCDD (10 nM) in a transient transfection assay. This regulatory region was fused to the cDNA sequence encoding green fluorescent protein (GFP) of jellyfish (Aequorea victoria). Transgenic zebrafish were generated to express this AhR-regulated GFP construct. Injected fish exposed to TCDD exhibited induction of GFP in the eye, nose, and vertebrae of zebrafish embryos (48 and 72 hr after fertilization) compared to vehicle controls (DMSO), which did not express GFP. To investigate whether AhR-regulated GFP expression correlated with sites of TCDD toxicity, we exposed wild-type zebrafish to DMSO or TCDD and examined them for morphologic abnormalities. By 5 days after fertilization, TCDD-exposed fish exhibited gross dysmorphogenesis in cranio-facial and vertebral development.

  8. Design and implementation of SMO for a nonlinear MIMO AHRS

    NASA Astrophysics Data System (ADS)

    Doostdar, Parisa; Keighobadi, Jafar

    2012-10-01

    In a low-cost attitude heading reference system (AHRS), the measurements made by MEMS inertial and magnetic sensors are affected by large parameter uncertainties, stochastic noises and unknown disturbances. In this paper, considering the robustness of the sliding mode observers (SMO) against both structured and unstructured uncertainties as well as exogenous inputs, the process of design and implementation of a nonlinear SMO is proposed for a low-cost AHRS. For simultaneous estimation of orientation variables and calibration biases of gyroscopes, a nonlinear and non-affine model of the AHRS is considered. Therefore, based on the Lie-algebraic method, the estimation algorithm is designed for a general class of non-affine nonlinear MIMO systems. In the proposed observer, owing to decreasing the required assumptions for coordinate transformation in recent literatures, the design process of the SMO is simplified. The gain matrices of the proposed SMO are obtained through ensuring the stability and the convergence of estimation errors based on Lyapunov's direct method. The expected tracking performance of the robust state and parameter estimation algorithm compared to that of the extended Kalman filter (EKF) is evaluated through simulations and real experiments of a strapped AHRS on a ground vehicle.

  9. Constitutive IDO expression in human cancer is sustained by an autocrine signaling loop involving IL-6, STAT3 and the AHR

    PubMed Central

    Sahm, Felix; Rauschenbach, Katharina J.; Trump, Saskia; Winter, Marcus; Ott, Martina; Ochs, Katharina; Lutz, Christian; Liu, Xiangdong; Anastasov, Natasa; Lehmann, Irina; Höfer, Thomas; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

    2014-01-01

    Indoleamine-2,3-dioxygenase (IDO) inhibitors have entered clinical trials based on their ability to restore anti-tumor immunity in preclinical studies. However, the mechanisms leading to constitutive expression of IDO in human tumors are largely unknown. Here we analyzed the pathways mediating constitutive IDO expression in human cancer. IDO-positive tumor cells and tissues showed basal phosphorylation and acetylation of STAT3 as evidenced by western blotting and immunoprecipitation. Inhibition of IL-6 or STAT3 using siRNA and/or pharmacological inhibitors reduced IDO mRNA and protein expression as well as kynurenine formation. In turn, IDO enzymatic activity activated the AHR as shown by the induction of AHR target genes. IDO-mediated AHR activation induced IL-6 expression, while inhibition or knockdown of the AHR reduced IL-6 expression. IDO activity thus sustains its own expression via an autocrine AHR–IL-6–STAT3 signaling loop. Inhibition of the AHR–IL-6–STAT3 signaling loop restored T-cell proliferation in mixed leukocyte reactions performed in the presence of IDO-expressing human cancer cells. Identification of the IDO-AHR-IL-6-STAT3 signaling loop maintaining IDO expression in human cancers reveals novel therapeutic targets for the inhibition of this core pathway promoting immunosuppression of human cancers. The relevance of the IDO-AHR-IL-6-STAT3 transcriptional circuit is underscored by the finding that high expression of its members IDO, STAT3 and the AHR target gene CYP1B1 is associated with reduced relapse-free survival in lung cancer patients. PMID:24657910

  10. Characterization testing of a 40 Ahr bipolar nickel hydrogen battery

    NASA Technical Reports Server (NTRS)

    Brewer, Jeffrey C.; Manzo, Michelle A.; Gahn, Randall F.

    1989-01-01

    In a continuing effort to develop NiH2 bipolar technology to a point where it can be used efficiently in space flight, testing of a second 40 Ahr, 10-cell bipolar battery has begun. This battery has undergone extensive characterization testing to determine the effects of such operating parameters as charge and discharge rates, temperature, and pressure. The fundamental design of this actively cooled bipolar battery is the same as the first battery. Most of the individual components, however, are from different manufacturers. Different testing procedures as well as certain unique battery characteristics make it difficult to directly compare the two sets of results. In general, the performance of this battery throughout characterization produced expected results. The main differences seen between the first and second batteries occurred during the high-rate discharge portion of the test matrix. The first battery also had poor high-rate discharge results, although better than those of the second battery. Minor changes were made to the battery frame design used for the first battery in an attempt to allow better gas access to the reaction sites for the second build and hopefully improve performance. The changes, however, did not improve the performance of the second battery and could have possibly contributed to the poorer performance that was observed. There are other component differences that could have contributed to the poorer performance of the second battery. The H2 electrode in the second battery was constructed with a Goretex backing which could have limited the high-rate current flow. The gas screen in the second battery had a larger mesh which again could have limited the high-rate current flow. Small scale 2 x 2 batteries are being tested to evaluate the effects of the component variations.

  11. The chlorinated AHR ligand 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) promotes reactive oxygen species (ROS) production during embryonic development in the killifish (Fundulus heteroclitus)

    USGS Publications Warehouse

    Arzuaga, Xabier; Wassenberg, Deena; Giulio, Richard D.; Elskus, Adria

    2006-01-01

    Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor (AHR) can result in increased cellular and tissue production of reactive oxygen species (ROS). Little is known of these effects during early fish development. We used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and pro-oxidant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) can increase ROS production during killifish development, and to test a novel method for measuring ROS non-invasively in a living organism. The superoxide-sensitive fluorescent dye, dihydroethidium (DHE), was used to detect in ovo ROS production microscopically in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM, with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations also significantly increased in ovo ROS production in embryonic liver, ROS being detectable as early as 5 days post-fertilization. These data demonstrate that the pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS production in developing killifish embryos. The superoxide detection assay (SoDA) described in this paper provides a semi-quantitative, easily measured, early indicator of altered ROS production that can be used in conjunction with simultaneous in ovo measurements of CYP1A activity and embryo development to explore functional relationships among biochemical, physiological and developmental responses to AHR ligands.

  12. 4-Nitrophenol exposure alters the AhR signaling pathway and related gene expression in the rat liver.

    PubMed

    Li, Ruonan; Song, Meiyan; Li, Zhi; Li, Yansen; Watanabe, Gen; Nagaoka, Kentaro; Taya, Kazuyoshi; Li, Chunmei

    2017-02-01

    4-Nitrophenol (PNP) is well known as an environmental endocrine disruptor. The aim of this study was to clarify the mechanism of PNP-induced liver damage and determine the regulatory involvement of the aryl hydrocarbon receptor (AhR) signaling pathway and associated gene expression. Immature male Wistar-Imamichi rats (28 days old) were randomly divided into control and PNP groups, which consisted of 1- and 3-day exposure (1 DE and 3 DE, respectively) and 3-day exposure followed by 3-day recovery (3 DE + 3 DR), groups. Each group was administered the vehicle or PNP (200 mg kg(-1) body weight). The body and liver weight were significantly decreased in the 3 DE group. The mRNA expression levels of estrogen receptor-α (ERα), glutathione S-transferase (GST) and AhR exhibited a significant increase in the 1 DE group whereas, in contrast, that of cytochrome P450 (CYP) 1A1 decreased significantly in the 3 DE +3 DR group. AhR and CYP1A1 proteins were detected in the cytoplasm of hepatocytes of the 1 DE and 3 DE +3 DR groups whereas the ERα protein was found in the hepatocyte nuclei of the 1 DE and 3 DE groups. The present study demonstrates that PNP activated the AhR signaling pathway and regulated related CYP1A1 and GST gene expression in the liver. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    SciTech Connect

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  14. Chemical activation of carbon mesophase pitches.

    PubMed

    Mora, E; Blanco, C; Pajares, J A; Santamaría, R; Menéndez, R

    2006-06-01

    This paper studies the chemical activation of mesophase pitches of different origins in order to obtain activated carbons suitable for use as electrodes in supercapacitors. The effect that the activating agent (NaOH, LiOH, and KOH), the alkaline hydroxide/pitch ratio, and the activation temperature had on the characteristics of the resultant activated carbons was studied. LiOH was found to be a noneffective activating agent, while activation with NaOH and KOH yielded activated carbons with high apparent surface areas and pore volumes. The increase of the KOH/pitch ratio caused an increase of the chemical attack on the carbon, producing higher burnoffs and development of porosity. Extremely high apparent surface areas were obtained when the petroleum pitch was activated with 5:1 KOH/carbon ratio. The increase of the activation temperature caused an increase of the burnoff, although the differences were not as significant as those derived from the use of different proportions of activating agent.

  15. Activated coconut shell charcoal carbon using chemical-physical activation

    NASA Astrophysics Data System (ADS)

    Budi, Esmar; Umiatin, Nasbey, Hadi; Bintoro, Ridho Akbar; Wulandari, Futri; Erlina

    2016-02-01

    The use of activated carbon from natural material such as coconut shell charcoal as metal absorbance of the wastewater is a new trend. The activation of coconut shell charcoal carbon by using chemical-physical activation has been investigated. Coconut shell was pyrolized in kiln at temperature about 75 - 150 °C for about 6 hours in producing charcoal. The charcoal as the sample was shieved into milimeter sized granule particle and chemically activated by immersing in various concentration of HCl, H3PO4, KOH and NaOH solutions. The samples then was physically activated using horizontal furnace at 400°C for 1 hours in argon gas environment with flow rate of 200 kg/m3. The surface morphology and carbon content of activated carbon were characterized by using SEM/EDS. The result shows that the pores of activated carbon are openned wider as the chemical activator concentration is increased due to an excessive chemical attack. However, the pores tend to be closed as further increasing in chemical activator concentration due to carbon collapsing.

  16. Deficiency in Aryl Hydrocarbon Receptor (AHR) Expression throughout Aging Alters Gene Expression Profiles in Murine Long-Term Hematopoietic Stem Cells

    PubMed Central

    Bennett, John A.; Singh, Kameshwar P.; Unnisa, Zeenath; Welle, Stephen L.; Gasiewicz, Thomas A.

    2015-01-01

    Dysregulation of hematopoietic stem cell (HSC) signaling can contribute to the development of diseases of the blood system. Lack of aryl hydrocarbon receptor (AhR) has been associated with alterations in gene expression related to HSC function and the subsequent development of a myeloproliferative disorder in aging female mice. We sorted the most primitive population of HSCs with the highest stem cell potential (Long-term, or LT-HSCs) from 18-month-old AhR-null-allele (AhR-KO) and WT mice and analyzed gene expression using microarray to determine alterations in gene expression and cell signaling networks in HSCs that could potentially contribute to the aging phenotype of AhR-KO mice. Comparisons with previous array data from 8-week old mice indicated that aging alone is sufficient to alter gene expression. In addition, a significant number of gene expression differences were observed in aged LT-HSCs that are dependent on both aging and lack of AhR. Pathway analysis of these genes revealed networks related to hematopoietic stem cell activity or function. qPCR was used to confirm the differential expression of a subset of these genes, focusing on genes that may represent novel AhR targets due to the presence of a putative AhR binding site in their upstream regulatory region. We verified differential expression of PDGF-D, Smo, Wdfy1, Zbtb37 and Zfp382. Pathway analysis of this subset of genes revealed overlap between cellular functions of the novel AhR targets and AhR itself. Lentiviral-mediated knockdown of AhR in lineage-negative hematopoietic cells was sufficient to induce changes in all five of the candidate AhR targets identified. Taken together, these data suggest a role for AhR in HSC functional regulation, and identify novel HSC AhR target genes that may contribute to the phenotypes observed in AhR-KO mice. PMID:26208102

  17. Benzimidazoisoquinolines: A New Class of Rapidly Metabolized Aryl Hydrocarbon Receptor (AhR) Ligands that Induce AhR-Dependent Tregs and Prevent Murine Graft-Versus-Host Disease

    PubMed Central

    Punj, Sumit; Kopparapu, Prasad; Jang, Hyo Sang; Phillips, Jessica L.; Pennington, Jamie; Rohlman, Diana; O’Donnell, Edmond; Iversen, Patrick L.; Kolluri, Siva Kumar; Kerkvliet, Nancy I.

    2014-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. The ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. To this end, we designed a screen for novel Treg-inducing compounds based on our understanding of the mechanisms of Treg induction by the well-characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We screened a ChemBridge small molecule library and identified 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a potent AhR ligand that was rapidly metabolized and not cytotoxic to proliferating T cells. Like TCDD,10-Cl-BBQ altered donor CD4+ T cell differentiation during the early stages of a graft versus host (GVH) response resulting in expression of high levels of CD25, CTLA-4 and ICOS, as well as several genes associated with Treg function. The Treg phenotype required AhR expression in the donor CD4+ T cells. Foxp3 was not expressed in the AhR-induced Tregs implicating AhR as an independent transcription factor for Treg induction. Structure-activity studies showed that unsubstituted BBQ as well as 4, 11-dichloro-BBQ were capable of inducing AhR-Tregs. Other substitutions reduced activation of AhR. Daily treatment with 10-Cl-BBQ during the GVH response prevented development of GVH disease in an AhR-dependent manner with no overt toxicity. Together, our data provide strong support for development of select BBQs that activate the AhR to induce Tregs for treatment of immune-mediated diseases. PMID:24586378

  18. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer.

    PubMed

    Spink, Barbara C; Bloom, Michael S; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n=2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n=4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility.

  19. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    PubMed Central

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n = 4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. PMID:25447411

  20. USE OF THE TEQ MODEL FOR ASSESSING AHR MEDIATED TOXICITY RISKS TO POPULATIONS OF LAKE TROUT AND OTHER SPECIES IN LAKE ONTARIO

    EPA Science Inventory

    The toxicity equivalence (TEQ) model for assessing aryl hydrocarbon receptor (AHR) mediated toxicity risks associated with polyhalogenated aromatic chemicals structurally similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been applied to human health risks for more than 15...

  1. Antimicrobial activity of chemically modified dextran derivatives.

    PubMed

    Tuchilus, Cristina G; Nichifor, Marieta; Mocanu, Georgeta; Stanciu, Magdalena C

    2017-04-01

    Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60μg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C12H25 or C18H37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups.

  2. Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins.

    PubMed

    Farmahin, Reza; Wu, Dongmei; Crump, Doug; Hervé, Jessica C; Jones, Stephanie P; Hahn, Mark E; Karchner, Sibel I; Giesy, John P; Bursian, Steven J; Zwiernik, Matthew J; Kennedy, Sean W

    2012-03-06

    There are large differences in sensitivity to the toxic and biochemical effects of dioxins and dioxin-like compounds (DLCs) among vertebrates. Previously, we demonstrated that the difference in sensitivity between domestic chicken (Gallus gallus domesticus) and common tern (Sterna hirundo) to aryl hydrocarbon receptor 1 (AHR1)-dependent changes in gene expression following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is based upon the identities of the amino acids at two sites within the ligand binding domain of AHR1 (chicken--highly sensitive; Ile324_Ser380 vs common tern--250-fold less sensitive than chicken; Val325_Ala381). Here, we tested the hypotheses that (i) the sensitivity of other avian species to TCDD, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) is also determined by the amino acids at sites that are equivalent to sites 324 and 380 in chicken, and (ii) Ile324_Ala380 and Val324_Ser380 genotypes confer intermediate sensitivity to DLCs in birds. We compared ligand-induced transactivation function of full-length AHR1s from chicken, common tern, ring-necked pheasant (Phasianus colchicus; Ile324_Ala380) and Japanese quail (Coturnix japonica; Val324_Ala380), and three Japanese quail AHR1 mutants. The results support our hypothesis that avian species can be grouped into three general classes of sensitivity to DLCs. Both AHR1 genotype and in vitro transactivation assays predict in vivo sensitivity. Contrary to the assumption that TCDD is the most potent DLC, PeCDF was more potent than TCDD at activating Japanese quail (13- to 26-fold) and common tern (23- to 30-fold) AHR1. Our results support and expand previous in vitro and in vivo work that demonstrated ligand-dependent species differences in AHR1 affinity. The findings and methods will be of use for DLC risk assessments.

  3. The Role of AHR in Breast Cancer Development

    DTIC Science & Technology

    2005-07-01

    cancer, AhR, galangin 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON OF ABSTRACT OF PAGES USAMRMC a. REPORT...Z39.18 ABSTRACT The study described herein was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin , affects growth of...human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon

  4. Insight into hydroxides-activated coals: chemical or physical activation?

    SciTech Connect

    Alcaniz-Monge, J.; Illan-Gomez, M.J.

    2008-02-15

    The objective of this paper is to get an insight into the chemical activation mechanism using KOH and NaOH as activated agents. Three coals have been selected as carbon precursors. It was found that KOH and NaOH develop a similar narrow microporosity, independently of the coal rank, whereas only KOH generates supermicroporosity. Temperature-programmed desorption experiments, carried out with impregnated anthracite, show differences on the gas evolved during the activated carbon preparation using the two activating agents. Thus, whereas hydrogen profiles are quite similar for both activated agents, the CO and H{sub 2}O profiles are different. It is remarkable the high amount of H{sub 2}O evolved at the maximum treatment temperature for both activating agents. The results obtained to allow conclusion that the chemical activation is due to a combination of different process driving the development of material porosity.

  5. Collective surfing of chemically active particles.

    PubMed

    Masoud, Hassan; Shelley, Michael J

    2014-03-28

    We study theoretically the collective dynamics of immotile particles bound to a 2D surface atop a 3D fluid layer. These particles are chemically active and produce a chemical concentration field that creates surface-tension gradients along the surface. The resultant Marangoni stresses create flows that carry the particles, possibly concentrating them. For a 3D diffusion-dominated concentration field and Stokesian fluid we show that the surface dynamics of active particle density can be determined using nonlocal 2D surface operators. Remarkably, we also show that for both deep or shallow fluid layers this surface dynamics reduces to the 2D Keller-Segel model for the collective chemotactic aggregation of slime mold colonies. Mathematical analysis has established that the Keller-Segel model can yield finite-time, finite-mass concentration singularities. We show that such singular behavior occurs in our finite-depth system, and study the associated 3D flow structures.

  6. A Photoacoustic Study of Chemically Active Systems.

    DTIC Science & Technology

    1983-09-01

    unless so designated by other documentation IS. KEY WORDS (Continue w reverse aide If neceeairy wd Identify by block nmber) Photoacoustic, Spectroscopy ...CwcAhnm i, pwo If w M Idntitty by block nin1b9) -,xThe method of gas-microphone photoacoustic spectroscopy and the related photothermal deflection... spectroscopy have been developed for application to chemically active systems. Fourier Transform Infrared Photoacoustic Spectros- copy has been used to study

  7. Chemically activated manganese dioxide for dry batteries

    NASA Astrophysics Data System (ADS)

    Askar, M.; Abbas, H.

    1994-10-01

    The present investigation has enabled us to convert inactive beta-manganese dioxide to high electrochemically active types by chemical processes. Natural and chemically prepared beta-manganese dioxides were roasted at 1050 C to form Mn3O4. This compound was subjected to activation treatment using hydrochloric and sulfuric acid under various reaction conditions. The manganese dioxide so obtained was examined by x-ray diffraction, thermogravimetric, differential thermal, and chemical analyses. The structure of the dioxide obtained was found to be greatly dependent on the origin of MnO2 and type of acid used. Treatment with hydrochloric acid yielded the so-called gamma-variety while sulfuric acid tended to produce gamma- or alpha-MnO2. In addition, waste manganese sulfate obtained as by-product from sulfuric acid digestion treatment was recycled and electrolytically oxidized to gamma-MnO2. The discharge performance of the above-mentioned MnO2 samples as battery cathodic active material was evaluated and compared with the ordinary battery grade.

  8. Chemical inhibition of nitrification in activated sludge.

    PubMed

    Kelly, R T; Henriques, I D S; Love, N G

    2004-03-20

    Conventional aerobic nitrification was adversely affected by single pulse inputs of six different classes of industrially relevant chemical toxins: an electrophilic solvent (1-chloro-2,4-dinitrobenzene, CDNB), a heavy metal (cadmium), a hydrophobic chemical (1-octanol), an uncoupling agent (2,4-dinitrophenol, DNP), alkaline pH, and cyanide in its weak metal complexed form. The concentrations of each chemical source that caused 1 5, 25, and 50% respiratory inhibition of a nitrifying mixed liquor during a short-term assay were used to shock sequencing batch reactors containing nitrifying conventional activated sludge. The reactors were monitored for recovery over a period of 30 days or less. All shock conditions inhibited nitrification, but to different degrees. The nitrate generation rate (NGR) of the shocked reactors recovered overtime to control reactor levels and showed that it was a more sensitive indicator of nitrification inhibition than both initial respirometric tests conducted on unexposed biomass and effluent nitrogen species analyses. CDNB had the most severe impact on nitrification, followed by alkaline pH 11, cadmium, cyanide, octanol, and DNP. Based on effluent data, cadmium and octanol primarily inhibited ammonia-oxidizing bacteria (AOB) while CDNB, pH 11,and cyanide inhibited both AOB and nitrite-oxidizing bacteria (NOB). DNP initially inhibited nitrification but quickly increased the NGR relative to the control and stimulated nitrification after several days in a manner reflective of oxidative uncoupling. The shocked mixed liquor showed trends toward recovery from inhibition for all chemicals tested, but in some cases this reversion was slow. These results contribute to our broader effort to identify relationships between chemical sources and the process effects they induce in activated sludge treatment systems.

  9. Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5

    SciTech Connect

    Oshima, Motohiko; Mimura, Junsei; Yamamoto, Masayuki; Fujii-Kuriyama, Yoshiaki

    2007-12-14

    The Aryl hydrocarbon receptor repressor (AhRR) has been proposed to inhibit Aryl hydrocarbon receptor (AhR) activity by competing with AhR for forming a heterodimer with AhR nuclear translocator (Arnt) and subsequently binding to the xenobiotic responsive elements (XRE). However, the precise mechanism of AhRR inhibitory activity remains unknown. Analysis of the inhibitory activity of AhRR on the expression of a TK promoter-driven reporter has localized a core repressor domain in the sequence of amino acid residue 555-701. The inhibitory activity of AhRR is sensitive to a histone deacetylase (HDAC) inhibitor, trichostatin A. By using the yeast two-hybrid screening method with the C-terminal sequence of AhRR as bait, we identified a binding partner, Ankyrin-repeat protein2 (ANKRA2), a protein known to interact with HDAC4 and HDAC5. RNA interference experiments using ANKRA2 and AhRR siRNAs indicate that ANKRA2 is important for transcriptional repression by AhRR. We have found that under normal conditions, CYP1A1 gene is kept silent in MEF cells by AhRR/Arnt heterodimer, which binds to the XRE sequence in its promoter and recruits ANKRA2, HDAC4, and HDAC5 as co-repressors.

  10. Chemical activation through super energy transfer collisions.

    PubMed

    Smith, Jonathan M; Nikow, Matthew; Ma, Jianqiang; Wilhelm, Michael J; Han, Yong-Chang; Sharma, Amit R; Bowman, Joel M; Dai, Hai-Lung

    2014-02-05

    Can a molecule be efficiently activated with a large amount of energy in a single collision with a fast atom? If so, this type of collision will greatly affect molecular reactivity and equilibrium in systems where abundant hot atoms exist. Conventional expectation of molecular energy transfer (ET) is that the probability decreases exponentially with the amount of energy transferred, hence the probability of what we label "super energy transfer" is negligible. We show, however, that in collisions between an atom and a molecule for which chemical reactions may occur, such as those between a translationally hot H atom and an ambient acetylene (HCCH) or sulfur dioxide, ET of chemically significant amounts of energy commences with surprisingly high efficiency through chemical complex formation. Time-resolved infrared emission observations are supported by quasi-classical trajectory calculations on a global ab initio potential energy surface. Results show that ∼10% of collisions between H atoms moving with ∼60 kcal/mol energy and HCCH result in transfer of up to 70% of this energy to activate internal degrees of freedom.

  11. Active Chemical Thermodynamics promoted by activity of cortical actin

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Bhaswati; Chaudhuri, Abhishek; Gowrishankar, Kripa; Rao, Madan

    2011-03-01

    The spatial distribution and dynamics of formation and breakup of the nanoclusters of cell surface proteins is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we have proposed a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. We study the consequences of such active actin-based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that the active remodeling of cortical actin, can give rise to a dramatic increase in efficiency and extent of conformational spread, even at low levels of expression at the cell surface. We define a activity temperature (τa) arising due to actin activities which can be used to describe chemical thermodynamics of the system. We plot TTT (time-temparature-transformation) curves and compute the Arrhenius factors which depend on τa . With this, the active asters can be treated as enzymes whose enzymatic reaction rate can be related to the activity.

  12. 76 FR 80447 - Eighth Meeting: RTCA Special Committee 219: Attitude and Heading Reference Systems (AHRS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ... Special Committee 219: Attitude and Heading Reference Systems (AHRS) AGENCY: Federal Aviation...: Attitude and Heading Reference Systems (AHRS). SUMMARY: The FAA is issuing this notice to advise the public of the eighth meeting of RTCA Special Committee 219: Attitude and Heading Reference Systems...

  13. Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

    PubMed

    Kamenickova, Alzbeta; Pecova, Michaela; Bachleda, Petr; Dvorak, Zdenek

    2013-12-01

    Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.

  14. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation

    PubMed Central

    Corrada, Dario; Soshilov, Anatoly A.; Denison, Michael S.

    2016-01-01

    The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

  15. Estimation of weekly 99Mo production by AHR 200 kW

    NASA Astrophysics Data System (ADS)

    Siregar, I. H.; Suharyana; Khakim, A.; Siregar, D.; Frida, A. R.

    2016-11-01

    The estimation of weekly 99Mo production by AHR 200 kW fueled with Low Enriched Uranium Uranyl Nitrate solution has been simulated by using MCNPX computer code. We have employed the AHR design of Babcock & Wilcox Medical Isotope Production System with 9Be Reflector and Stainless steel vessel. We found that when the concentration of uranium in the fresh fuel was 108 gr U/L of UO2(NO3)2 fuel solution, the multiplication factor was 1.0517. The 99Mo concentration reached saturated at tenth day operation. The AHR can produce approximately 1.96×103 6-day-Ci weekly.

  16. The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3' Immunoglobulin Heavy Chain Regulatory Region.

    PubMed

    Salisbury, Richard L; Sulentic, Courtney E W

    2015-12-01

    Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3'Igh regulatory region (3'IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-κB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3'IghRR and hs1.2 enhancer activation induced by the B-lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-κB/Rel binding site suggesting a potential reciprocal modulation of the 3'IghRR by AhR and NF-κB/Rel. The objective of the current study was to evaluate the role of NF-κB/Rel and the AhR on the 3'IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3'IghRR-regulated transgene reporter or an inducible IκBα (inhibitor kappa B-alpha protein) superrepressor (IκBαAA), we demonstrate an AhR- and NF-κB/Rel-dependent modulation of 3'IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-κB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-κB/Rel protein binding profile within the 3'IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels.

  17. The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3′ Immunoglobulin Heavy Chain Regulatory Region

    PubMed Central

    Salisbury, Richard L.; Sulentic, Courtney E. W.

    2015-01-01

    Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3′Igh regulatory region (3′IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-κB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3′IghRR and hs1.2 enhancer activation induced by the B-lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-κB/Rel binding site suggesting a potential reciprocal modulation of the 3′IghRR by AhR and NF-κB/Rel. The objective of the current study was to evaluate the role of NF-κB/Rel and the AhR on the 3′IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3′IghRR-regulated transgene reporter or an inducible IκBα (inhibitor kappa B-alpha protein) superrepressor (IκBαAA), we demonstrate an AhR- and NF-κB/Rel-dependent modulation of 3′IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-κB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-κB/Rel protein binding profile within the 3′IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels. PMID:26377645

  18. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    SciTech Connect

    Cheng, Xingguo; Vispute, Saurabh G.; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D.

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.

  19. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Giesy, John P; Hecker, Markus

    2014-05-01

    Sturgeons are ancient fishes, which are endangered in many parts of the world. Due to their benthic nature and longevity, sturgeon are at great risk of exposure to bioaccumulative contaminants such as dioxin-like compounds (DLCs). Despite their endangered status, little research has been conducted to characterize the relative sensitivity of sturgeons to DLCs. Proper assessment of risk of DLCs posed to these fishes therefore, requires a better understanding of this sensitivity and the factors that are driving it. Adverse effects associated with exposure to DLCs are mediated by the aryl hydrocarbon receptor (AhR). This study identified and characterized two distinct AhRs, AhR1 and AhR2, in white sturgeon (Acipenser transmontanus) for the first time as a first step in studying the relative sensitivities of sturgeons to DLCs. Furthermore, tissue-specific expression of both AhRs under basal conditions and in response to exposure to the model DLC, β-naphthoflavone (βNF), was determined. The sequence of amino acids of AhR1 of white sturgeon had greater similarity to AhRs of tetrapods, including amphibians, birds, and mammals, than to AhR1s of other fishes. The sequence of amino acids in the ligand binding domain of the AhR1 had greater than 80% similarity to AhRs known to bind DLCs and was less similar to AhRs not known to bind DLCs. AhR2 of white sturgeon had greatest similarity to AhR2 of other fishes. Profiles of expression of AhR1 and AhR2 in white sturgeon were distinct from those known in other fishes and appear more similar to profiles observed in birds. Expressions of both AhR1 and AhR2 of white sturgeon were greatest in liver and heart, which are target organs for DLCs. Furthermore, abundances of transcripts of AhR1 and AhR2 in all tissues from white sturgeon were greater than controls (up to 35-fold) following exposure to βNF. Based upon both AhRs having similar abundances of transcript in target organs of DLC toxicity, both AhRs being up-regulated following

  20. SOME CHEMICAL PROPERTIES UNDERLYING ARSENIC'S BIOLOGICAL ACTIVITY

    EPA Science Inventory

    ABSTRACT

    In this paper some of the chemical properties of arsenicals (atomic
    and molecular orbitals, electronegativity, valence state, changes between
    valence state, nucleophilicity, the hard/soft acid/base principle) that may
    account for some of the b...

  1. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

    PubMed Central

    Hubbard, Troy D.; Murray, Iain A.

    2015-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High-affinity ligands of AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiologic functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract. PMID:26041783

  2. Specific Ligand Binding Domain Residues Confer Low Dioxin Responsiveness to AHR1β of Xenopus laevis

    PubMed Central

    Odio, Camila; Holzman, Sarah A.; Denison, Michael S.; Fraccalvieri, Domenico; Bonati, Laura; Franks, Diana G.; Hahn, Mark E.; Powell, Wade H.

    2013-01-01

    The aryl hydrocarbon receptor (AHR) is a PAS-family protein that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vertebrates. Frogs are remarkably insensitive to TCDD, and AHRs from Xenopus laevis bind TCDD with low affinity. We sought to identify structural features of X. laevis AHR1β associated with low TCDD sensitivity. Substitution of the entire ligand-binding domain (LBD) with the corresponding sequence from mouse AHRb-1 dramatically increased TCDD responsiveness in transactivation assays. To identify amino acid residues responsible, we constructed a comparative model of the AHR1β LBD using homologous domains of PAS proteins HIF2α and ARNT. The model revealed an internal cavity of similar dimensions to the putative binding cavity of mouse AHRb-1, suggesting the importance of side-chain interactions over cavity size. Of residues with side chains clearly pointing into the cavity, only two differed from the mouse sequence. When A354, located within a conserved β-strand, was changed to serine, the corresponding mouse residue, the EC50 for TCDD decreased more than 15-fold. When N325 was changed to serine, EC50 declined 3-fold. When the mutations were combined, the EC50 declined from 18.6 nM to 0.8 nM, nearly matching mouse AHR for TCDD sensitivity. Velocity sedimentation analysis confirmed that mutant frog AHRs exhibited correspondingly increased TCDD binding. We also assayed mutant AHRs for responsiveness to a candidate endogenous ligand, 6-formylindolo[3,2b]carbazole (FICZ). Mutations that increased TCDD sensitivity also increased sensitivity to FICZ. This comparative study represents a novel approach to discerning fundamental information about the structure of AHR and its interactions with biologically important agonists. PMID:23394719

  3. ILO activities in the area of chemical safety.

    PubMed

    Obadia, Isaac

    2003-08-21

    The ILO has been active in the area of safety in the use of chemicals at work since the year of its creation in 1919, including the development of international treaties and other technical instruments, the provision of technical assistance to its member States, and the development of chemical safety information systems. The two key ILO standards in this area are the Conventions on safety in the use of chemicals at work (No. 170, 1990), and the Prevention of Major Industrial Accidents (No. 174, 1993). The ILO Programme on occupational safety, health and environment (Safe Work) is currently responsible for ILO chemical safety activities. In the past two decades, most of ILO work in this area has been carried out within the context of inter-agency collaboration frameworks linking the ILO, WHO, UNEP, FAO, UNIDO, UNITAR, and the OECD, including the International Programme on Chemical Safety (IPCS), the Inter-Organisation Programme for the Sound Management of Chemicals (IOMC), and the Intergovernmental Forum on Chemical Safety (IFCS). Apart from the regular development, updating and dissemination of chemical safety information data bases such as the IPCS International Chemical Cards, the elaboration of a Globally harmonized system for the classification and labelling of Chemicals (GHS) has been the most outstanding achievement of this international collaboration on chemical safety.

  4. Assessment of potential biological activities and distributions of endocrine-disrupting chemicals in sediments of the west coast of South Korea.

    PubMed

    Jeon, Seungyeon; Hong, Seongjin; Kwon, Bong-Oh; Park, Jinsoon; Song, Sung Joon; Giesy, John P; Khim, Jong Seong

    2017-02-01

    The west coast of Korea has experienced environmental deterioration for more than half a century. In the present study, we specifically aimed to: i) evaluate potential toxicities of contaminants in sediments that cause effects mediated through the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER); ii) determine spatio-temporal distributions of polycyclic aromatic hydrocarbons (PAHs) and alkylphenols (APs); and iii) identify causes of greater potencies of samples. From 2010 to 2014, sediments were collected from 12 major estuarine and coastal regions along the west coast of South Korea. In vitro cell bioassays were performed to determine AhR- and ER-mediated potencies using H4IIE-luc and MVLN cells, respectively. Fifteen PAHs and six APs in sediments were identified by GC/MSD. Results of bioassays generally showed a low-to-moderate degree of contamination, however, greater AhR- and ER-mediated potencies were measured at some locations. Concentrations of PAHs and APs varied among locations, which indicated that sources were independently affected by the surrounding environment (e.g., industrial complex and cities). Results of bioassays were generally well correlated with concentrations of putative causative chemicals. Benzo[k]fluoranthene, dibenz[a,h]anthracene, and benzo[b]fluoranthene were the major AhR agonists, explaining approximately 30% of the bioassay-derived benzo[a]pyrene equivalent concentration (BaP-EQ). Unknown AhR and ER agonists and potential mixture effects remain in question. Overall, the present study provides baseline information on chemical contaminations and potential toxicity of sediments in a fairly wide geographical region of the west coast of South Korea.

  5. Activating secondary metabolism with stress and chemicals.

    PubMed

    Yoon, Vanessa; Nodwell, Justin R

    2014-02-01

    The available literature on the secondary or nonessential metabolites of the streptomycetes bacteria suggests that there may be poorly expressed or "cryptic" compounds that have yet to be identified and that may have significant medical utility. In addition, it is clear that there is a large and complex regulatory network that controls the production of these molecules in the laboratory and in nature. Two approaches that have been taken to manipulating the yields of secondary metabolites are the use of various stress responses and, more recently, the use of precision chemical probes. Here, we review the status of this work and outline the challenges and opportunities afforded by each of them.

  6. The aryl hydrocarbon receptor (AhR) inhibits vanadate-induced vascular endothelial growth factor (VEGF) production in TRAMP prostates

    PubMed Central

    Fritz, Wayne A.; Lin, Tien-Min; Peterson, Richard E.

    2008-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT) are basic helix-loop-helix/per-arnt-sim (PAS) family transcription factors. During angiogenesis and tumor growth, HIF-1α dimerizes with ARNT, inducing expression of many genes, including vascular endothelial growth factor (VEGF). ARNT also dimerizes with the aryl hydrocarbon receptor (AhR). AhR-null (Ahr−/−) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice develop prostate tumors with greater frequency than AhR wild-type (Ahr+/+) TRAMP mice, even though prevalence of prostate epithelial hyperplasia is not inhibited. This suggests that Ahr inhibits prostate carcinogenesis. In TRAMP mice, prostatic epithelial hyperplasia results in stabilized HIF-1α, inducing expression of VEGF, a prerequisite for tumor growth and angiogenesis. Since ARNT is a common dimerization partner of AhR and HIF-1α, we hypothesized that the AhR inhibits prostate tumor formation by competing with HIF-1α for ARNT, thereby limiting VEGF production. Prostates from Ahr+/+, Ahr+/− and Ahr−/− C57BL/6J TRAMP mice were cultured in the presence of graded concentrations of vanadate, an inducer of VEGF through the HIF-1α–ARNT pathway. Vanadate induced VEGF protein in a dose-dependent fashion in Ahr+/− and Ahr−/− TRAMP cultures, but not in Ahr+/+ cultures. However, vanadate induced upstream proteins in the phosphatidylinositol 3-kinase-signaling cascade to a similar extent in TRAMPs of each Ahr genotype, evidenced by v-akt murine thymoma viral oncogene homolog (Akt) phosphorylation. These findings suggest that AhR sequesters ARNT, decreasing interaction with HIF-1α reducing VEGF production. Since VEGF is required for tumor vascularization and growth, these studies further suggest that reduction in VEGF correlates with inhibited prostate carcinogenesis in Ahr+/+ TRAMP mice. PMID:18359762

  7. Influence of process parameters on the surface and chemical properties of activated carbon obtained from biochar by chemical activation.

    PubMed

    Angın, Dilek; Altintig, Esra; Köse, Tijen Ennil

    2013-11-01

    Activated carbons were produced from biochar obtained through pyrolysis of safflower seed press cake by chemical activation with zinc chloride. The influences of process variables such as the activation temperature and the impregnation ratio on textural and chemical-surface properties of the activated carbons were investigated. Also, the adsorptive properties of activated carbons were tested using methylene blue dye as the targeted adsorbate. The experimental data indicated that the adsorption isotherms are well described by the Langmuir equilibrium isotherm equation. The optimum conditions resulted in activated carbon with a monolayer adsorption capacity of 128.21 mg g(-1) and carbon content 76.29%, while the BET surface area and total pore volume corresponded to 801.5m(2)g(-1) and 0.393 cm(3)g(-1), respectively. This study demonstrated that high surface area activated carbons can be prepared from the chemical activation of biochar with zinc chloride as activating agents.

  8. TSCA Chemical Data Reporting Fact Sheet: Reporting Manufactured Chemical Substances from Metal Mining and Related Activities

    EPA Pesticide Factsheets

    This fact sheet provides guidance on the Chemical Data Reporting (CDR) rule requirements related to the reporting of mined metals, intermediates, and byproducts manufactured during metal mining and related activities.

  9. Chemically-related Groups of Active Ingredients

    EPA Pesticide Factsheets

    Many pesticide active ingredients affect pests in similar ways, and we re-evaluate them together as a group. Groups include carbamate insecticides, neonicotinoids, organochlorines, organophosphates, pyrethrins, and pyrethroids.

  10. Genome-Wide RNAi High-Throughput Screen Identifies Proteins Necessary for the AHR-Dependent Induction of CYP1A1 by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    PubMed Central

    Hankinson, Oliver

    2013-01-01

    The aryl hydrocarbon receptor (AHR) has a plethora of physiological roles, and upon dysregulation, carcinogenesis can occur. One target gene of AHR encodes the xenobiotic and drug-metabolizing enzyme CYP1A1, which is inducible by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via the AHR. An siRNA library targeted against over 5600 gene candidates in the druggable genome was used to transfect mouse Hepa-1 cells, which were then treated with TCDD, and subsequently assayed for CYP1A1-dependent ethoxyresorufin-o-deethylase (EROD) activity. Following redundant siRNA activity (RSA) statistical analysis, we identified 93 hits that reduced EROD activity with a p value ≤ .005 and substantiated 39 of these as positive hits in a secondary screening using endoribonuclease-prepared siRNAs (esiRNAs). Twelve of the corresponding gene products were subsequently confirmed to be necessary for the induction of CYP1A1 messenger RNA by TCDD. None of the candidates were deficient in aryl hydrocarbon nuclear translocator expression. However 6 gene products including UBE2i, RAB40C, CRYGD, DCTN4, RBM5, and RAD50 are required for the expression of AHR as well as for induction of CYP1A1. We also found 2 gene products, ARMC8 and TCF20, to be required for the induction of CYP1A1, but our data are ambiguous as to whether they are required for the expression of AHR. In contrast, SIN3A, PDC, TMEM5, and CD9 are not required for AHR expression but are required for the induction of CYP1A1, implicating a direct role in Cyp1a1 transcription. Our methods, although applied to Cyp1a1, could be modified for identifying proteins that regulate other inducible genes. PMID:23997114

  11. An altered hydrotropic response (ahr1) mutant of Arabidopsis recovers root hydrotropism with cytokinin

    PubMed Central

    Saucedo, Manuel; Ponce, Georgina; Campos, María Eugenia; Eapen, Delfeena; García, Edith; Luján, Rosario; Sánchez, Yoloxóchitl; Cassab, Gladys I.

    2012-01-01

    Roots are highly plastic and can acclimate to heterogeneous and stressful conditions. However, there is little knowledge of the effect of moisture gradients on the mechanisms controlling root growth orientation and branching, and how this mechanism may help plants to avoid drought responses. The aim of this study was to isolate mutants of Arabidopsis thaliana with altered hydrotropic responses. Here, altered hydrotropic response 1 (ahr1), a semi-dominant allele segregating as a single gene mutation, was characterized. ahr1 directed the growth of its primary root towards the source of higher water availability and developed an extensive root system over time. This phenotype was intensified in the presence of abscisic acid and was not observed if ahr1 seedlings were grown in a water stress medium without a water potential gradient. In normal growth conditions, primary root growth and root branching of ahr1 were indistinguishable from those of the wild type (wt). The altered hydrotropic growth of ahr1 roots was confirmed when the water-rich source was placed at an angle of 45° from the gravity vector. In this system, roots of ahr1 seedlings grew downward and did not display hydrotropism; however, in the presence of cytokinins, they exhibited hydrotropism like those of the wt, indicating that cytokinins play a critical role in root hydrotropism. The ahr1 mutant represents a valuable genetic resource for the study of the effects of cytokinins in the differential growth of hydrotropism and control of lateral root formation during the hydrotropic response. PMID:22442413

  12. AHR2-Mediated Transcriptomic Responses Underlying the Synergistic Cardiac Developmental Toxicity of PAHs

    PubMed Central

    Jayasundara, Nishad; Van Tiem Garner, Lindsey; Meyer, Joel N.; Erwin, Kyle N.; Di Giulio, Richard T.

    2015-01-01

    Polycyclic aromatic hydrocarbons (PAHs) induce developmental defects including cardiac deformities in fish. The aryl hydrocarbon receptor (AHR) mediates the toxicity of some PAHs. Exposure to a simple PAH mixture during embryo development consisting of an AHR agonist (benzo(a)pyrene-BaP) with fluoranthene (FL), an inhibitor of cytochrome p450 1(CYP1)—a gene induced by AHR activation—results in cardiac deformities. Exposure to BaP or FL alone at similar concentrations alters heart rates, but does not induce morphological deformities. Furthermore, AHR2 knockdown prevents the toxicity of BaP + FL mixture. Here, we used a zebrafish microarray analysis to identify heart-specific transcriptomic changes during early development that might underlie cardiotoxicity of BaP + FL. We used AHR2 morphant embryos to determine the role of this receptor in mediating toxicity. Control and knockdown embryos at 36 h post-fertilization were exposed to DMSO, 100 μg/l BaP, 500 μg/l FL, or 100 μg/l BaP + 500 μg/l FL, and heart tissues for RNA were extracted at 2, 6, 12, and 18 h-post-exposure (hpe), prior to the appearance of cardiac deformities. Data show AHR2-dependent BaP + FL effects on expression of genes involved in protein biosynthesis and neuronal development in addition to signaling molecules and their associated molecular pathways. Ca2+-cycling and muscle contraction genes were the most significantly differentially expressed category of transcripts when comparing BaP + FL-treated AHR2 morphant and control embryos. These differences were most prominent at 2 and 6 hpe. Therefore, we postulate that BaP + FL may affect cellular Ca2+ levels and subsequently cardiac muscle function, potentially underlying BaP + FL cardiotoxicity. PMID:25412620

  13. Chemical Classification of Nearby Active Galaxies

    NASA Astrophysics Data System (ADS)

    Aladro, R.; Martín, S.; Kramer, C.

    2015-12-01

    We present an unbiased λ=3 mm survey done with the IRAM 30 telescope towards the central parts of eight galaxies considered as archetypes of nearby starbursts, galaxies with an active galactic nucleus (AGN) and ultra-luminous infrared galaxies (ULIRGs). The spatial resolution range from ˜200 pc to ˜1.6 kpc, depending on the galaxy. We compare the abundances of thirty-seven species among the sample, and highlight the molecules that characterise the gas in each of them. These results can be very useful to prepare future interferometric observations of active galaxies.

  14. Gas and Chemical Activation of Charcoal

    DTIC Science & Technology

    1945-06-29

    supplemented ’ by runs in the laboratory has shown that zinc chloride is by far the most suitable activating agent. 1. In the dehydration mixing of...istics with time of dehydration . 3. The physical appearance of the mixture during the impregnation pperation provides sufficient significant information...to enable the operator to predict .mechanical characteristics of the briquet. CONFIDENTIAL " • ’< i£: • CONFIDENTIAL -4- 4* In the dehydration

  15. 75 FR 69630 - Impact of Implementation of the Chemical Weapons Convention on Commercial Activities Involving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ...-0543-02] Impact of Implementation of the Chemical Weapons Convention on Commercial Activities Involving... Chemical Weapons Convention (CWC), through the Chemical Weapons Convention Implementation Act (CWCIA) and the Chemical Weapons Convention Regulations (CWCR), has had on commercial activities...

  16. Regulation of zebrafish CYP3A65 transcription by AHR2

    SciTech Connect

    Chang, Chin-Teng; Chung, Hsin-Yu; Su, Hsiao-Ting; Tseng, Hua-Pin; Tzou, Wen-Shyong; Hu, Chin-Hwa

    2013-07-15

    CYP3A proteins are the most abundant CYPs in the liver and intestines, and they play a pivotal role in drug metabolism. In mammals, CYP3A genes are induced by various xenobiotics through processes mediated by PXR. We previously identified zebrafish CYP3A65 as a CYP3A ortholog that is constitutively expressed in gastrointestinal tissues, and is upregulated by treatment with dexamethasone, rifampicin or tetrachlorodibenzo-p-dioxin (TCDD). However, the underlying mechanism of TCDD-mediated CYP3A65 transcription is unclear. Here we generated two transgenic zebrafish, Tg(CYP3A65S:EGFP) and Tg(CYP3A65L:EGFP), which contain 2.1 and 5.4 kb 5′ flanking sequences, respectively, of the CYP3A65 gene upstream of EGFP. Both transgenic lines express EGFP in larval gastrointestinal tissues in a pattern similar to that of the endogenous CYP3A65 gene. Moreover, EGFP expression can be significantly induced by TCDD exposure during the larval stage. In addition, EGFP expression can be stimulated by kynurenine, a putative AHR ligand produced during tryptophan metabolism. AHRE elements in the upstream regulatory region of the CYP3A65 gene are indispensible for basal and TCDD-induced transcription. Furthermore, the AHR2 DNA and ligand-binding domains are required to mediate effective CYP3A65 transcription. AHRE sequences are present in the promoters of many teleost CYP3 genes, but not of mammalian CYP3 genes, suggesting that AHR/AHR2-mediated transcription is likely a common regulatory mechanism for teleost CYP3 genes. It may also reflect the different environments that terrestrial and aquatic organisms encounter. - Highlights: • Tg(CYP3A65:EGFP) and CYP3A65 exhibits identical expression pattern. • CYP3A65 can be significantly induced by TCDD or kynurenine. • The AHRE elements are required to mediate CYP3A65 transcription. • The AHR2 DNA and ligand-binding domains are required for CYP3A65 transcription. • AHRE elements are present in many teleost CYP3 genes, but not in

  17. Genetic variation at aryl hydrocarbon receptor (AHR) loci in populations of Atlantic killifish (Fundulus heteroclitus) inhabiting polluted and reference habitats

    PubMed Central

    2014-01-01

    Background The non-migratory killifish Fundulus heteroclitus inhabits clean and polluted environments interspersed throughout its range along the Atlantic coast of North America. Several populations of this species have successfully adapted to environments contaminated with toxic aromatic hydrocarbon pollutants such as polychlorinated biphenyls (PCBs). Previous studies suggest that the mechanism of resistance to these and other “dioxin-like compounds” (DLCs) may involve reduced signaling through the aryl hydrocarbon receptor (AHR) pathway. Here we investigated gene diversity and evidence for positive selection at three AHR-related loci (AHR1, AHR2, AHRR) in F. heteroclitus by comparing alleles from seven locations ranging over 600 km along the northeastern US, including extremely polluted and reference estuaries, with a focus on New Bedford Harbor (MA, USA), a PCB Superfund site, and nearby reference sites. Results We identified 98 single nucleotide polymorphisms within three AHR-related loci among all populations, including synonymous and nonsynonymous substitutions. Haplotype distributions were spatially segregated and F-statistics suggested strong population genetic structure at these loci, consistent with previous studies showing strong population genetic structure at other F. heteroclitus loci. Genetic diversity at these three loci was not significantly different in contaminated sites as compared to reference sites. However, for AHR2 the New Bedford Harbor population had significant FST values in comparison to the nearest reference populations. Tests for positive selection revealed ten nonsynonymous polymorphisms in AHR1 and four in AHR2. Four nonsynonymous SNPs in AHR1 and three in AHR2 showed large differences in base frequency between New Bedford Harbor and its reference site. Tests for isolation-by-distance revealed evidence for non-neutral change at the AHR2 locus. Conclusion Together, these data suggest that F. heteroclitus populations in reference

  18. Tetrapleura tetraptera: molluscicidal activity and chemical constituents.

    PubMed

    Aladesanmi, Adetunji J

    2006-08-28

    Tetrapleura tetraptera (Schumach. And Thonn) Taub, Mimosaceae, commonly known as Aridan (fruit), A single stemmed, robust, perennial tree of about 30 m. It has a grey/brown, smooth/rough bark with glabrous yound branchlets. The flower is yellow/pink and racemes white the fruit has dark brown, four winged pods 12-25 x 3.5-6.5 cm. It is generally found in the lowland forest of tropical Africa. The fruit consists of a fleshy pulp with small, brownish-black seeds. The fruit possesses a fragrant, characteristically pungent aromatic odour, which is attributed to its insect repellent property. It is used as spices and aroma (exotic tropical scents) and fish poisoning. It is one of the molluscicidal medicinal plants of Nigeria, also useful in the management of convulsions, leprosy, inflammation and/or rheumatoid pains. The documented biological and-or pharmacological activities are found to be molluscicidal, cardio-vascular, neuromuscular, hypotensive, anti-convulsant, trypanocidal, hirudinicidal, schistosomiasis control, anti-ulcerative, ectoxicity, anti-inflammatory, hypoglycaemic, anti-microbial, emulsifying property, birth control, food value and the control of intestinal parasites. Activity-guided fractionation of the methanol extract of the fruits of T. tetraptera led to the isolation of a saponin glycoside with an oleanolic acid aglycone, a monodesmosidic diglycoside of the rare sapogenin 27-hydroxyolean-12 (13)-en-28-oic acid; echinocystic acid-3-0-sodium sulfate from the stembark, umbelliferone and ferulic acid from the leaves and branches respectively. Also isolated from the fruits were aridanin and three of its olean-12-en-28-oic acid derivatives. All the compounds isolated either from the fruits or other parts were found to exhibit strong molluscicidal properties against the schistosomiasis-transmitting snails Biomphalaria glabrata.

  19. Activated chemical defenses suppress herbivory on freshwater red algae.

    PubMed

    Goodman, Keri M; Hay, Mark E

    2013-04-01

    The rapid life cycles of freshwater algae are hypothesized to suppress selection for chemical defenses against herbivores, but this notion remains untested. Investigations of chemical defenses are rare for freshwater macrophytes and absent for freshwater red algae. We used crayfish to assess the palatability of five freshwater red algae relative to a palatable green alga and a chemically defended aquatic moss. We then assessed the roles of structural, nutritional, and chemical traits in reducing palatability. Both native and non-native crayfish preferred the green alga Cladophora glomerata to four of the five red algae. Batrachospermum helminthosum, Kumanoa holtonii, and Tuomeya americana employed activated chemical defenses that suppressed feeding by 30-60 % following damage to algal tissues. Paralemanea annulata was defended by its cartilaginous structure, while Boldia erythrosiphon was palatable. Activated defenses are thought to reduce ecological costs by expressing potent defenses only when actually needed; thus, activation might be favored in freshwater red algae whose short-lived gametophytes must grow and reproduce rapidly over a brief growing season. The frequency of activated chemical defenses found here (three of five species) is 3-20× higher than for surveys of marine algae or aquatic vascular plants. If typical for freshwater red algae, this suggests that (1) their chemical defenses may go undetected if chemical activation is not considered and (2) herbivory has been an important selective force in the evolution of freshwater Rhodophyta. Investigations of defenses in freshwater rhodophytes contribute to among-system comparisons and provide insights into the generality of plant-herbivore interactions and their evolution.

  20. Spontaneous and specific activation of chemical bonds in macromolecular fluids.

    PubMed

    Park, Insun; Shirvanyants, David; Nese, Alper; Matyjaszewski, Krzysztof; Rubinstein, Michael; Sheiko, Sergei S

    2010-09-08

    Mechanical activation of chemical bonds typically involves the application of external forces, which implies a broad distribution of bond tensions. We demonstrate that controlling the flow profile of a macromolecular fluid generates and delineates mechanical force concentration, enabling a hierarchical activation of chemical bonds on different length scales from the macroscopic to the molecular. Bond tension is spontaneously generated within brushlike macromolecules as they spread on a solid substrate. The molecular architecture creates an uneven distribution of tension in the covalent bonds, leading to spatially controlled bond scission. By controlling the flow rate and the gradient of the film pressure, one can sever the flowing macromolecules with high precision. Specific chemical bonds are activated within distinct macromolecules located in a defined area of a thin film. Furthermore, the flow-controlled loading rate enables quantitative analysis of the bond activation parameters.

  1. AHR Over-Expression in Papillary Thyroid Carcinoma: Clinical and Molecular Assessments in a Series of Italian Acromegalic Patients with a Long-Term Follow-Up

    PubMed Central

    Mian, Caterina; Ceccato, Filippo; Barollo, Susi; Watutantrige-Fernando, Sara; Albiger, Nora; Regazzo, Daniela; de Lazzari, Paola; Pennelli, Gianmaria; Rotondi, Sandra; Nacamulli, Davide; Pelizzo, Maria Rosa; Jaffrain-Rea, Marie-Lise; Grimaldi, Franco; Occhi, Gianluca; Scaroni, Carla

    2014-01-01

    Aim Acromegaly reportedly carries an increased risk of malignant and benign thyroid tumors, with a prevalence of thyroid cancer of around 3–7%. Germline mutations in the aryl-hydrocarbon receptor (AHR) interacting protein (AIP) have been identified in familial forms of acromegaly. The molecular and endocrine relationships between follicular thyroid growth and GH-secreting pituitary adenoma have yet to be fully established. Our aim was to study the prevalence of differentiated thyroid cancer (DTC) in acromegaly, focusing on the role of genetic events responsible for the onset of thyroid cancer. Methods Germline mutations in the AIP gene were assessed in all patients; BRAF and H-N-K RAS status was analyzed by direct sequencing in thyroid specimens, while immunohistochemistry was used to analyze the protein expression of AIP and AHR. A set of PTCs unrelated to acromegaly was also studied. Results 12 DTCs (10 papillary and 2 follicular carcinomas) were identified in a cohort of 113 acromegalic patients. No differences in GH/IGF-1 levels or disease activity emerged between patients with and without DTC, but the former were older and more often female. BRAF V600E was found in 70% of the papillary thyroid cancers; there were no RAS mutations. AIP protein expression was similar in neoplastic and normal cells, while AHR protein was expressed more in PTCs carrying BRAF mutations than in normal tissue, irrespective of acromegaly status. Conclusions The prevalence of DTC in acromegaly is around 11% and endocrinologists should bear this in mind, especially when examining elderly female patients with uninodular goiter. The DTC risk does not seem to correlate with GH/IGF-1 levels, while it may be associated with BRAF mutations and AHR over-expression. Genetic or epigenetic events probably play a part in promoting thyroid carcinoma. PMID:25019383

  2. In silico predictive studies of mAHR congener binding using homology modelling and molecular docking.

    PubMed

    Panda, Roshni; Cleave, A Suneetha Susan; Suresh, P K

    2014-09-01

    The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies.

  3. Endocrine-active chemicals in mammary cancer causation and prevention.

    PubMed

    Jenkins, Sarah; Betancourt, Angela M; Wang, Jun; Lamartiniere, Coral A

    2012-04-01

    Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'.

  4. Quantitative genetic activity graphical profiles for use in chemical evaluation

    SciTech Connect

    Waters, M.D.; Stack, H.F.; Garrett, N.E.; Jackson, M.A.

    1990-12-31

    A graphic approach, terms a Genetic Activity Profile (GAP), was developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose or highest ineffective dose is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for producing and evaluating genetic activity profile was developed in collaboration with the International Agency for Research on Cancer (IARC). Data on individual chemicals were compiles by IARC and by the US Environmental Protection Agency (EPA). Data are available on 343 compounds selected from volumes 1-53 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar profiles of genetic activity. Through examination of the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluation of chemical analogs. GAPs provided useful data for development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from an assessment of the genetic activity profiles of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines. 36 refs., 2 figs.

  5. Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway.

    PubMed

    Clark, Bryan W; Bone, A J; Di Giulio, R T

    2014-12-01

    Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Superfund site on the Elizabeth River (Portsmouth, VA, USA) are exposed to a complex mixture of polycyclic aromatic hydrocarbons (PAHs) from former creosote operations, but are resistant to the acute toxicity and cardiac teratogenesis caused by PAHs. The resistance is associated with a dramatic recalcitrance to induction of cytochrome P450 (CYP1) metabolism enzymes following exposure to aryl hydrocarbon receptor (AHR) agonists, along with an elevated antioxidant response and increased expression of several other xenobiotic metabolism and excretion enzymes. However, the heritability of the resistance in the absence of chemical stressors has been inconsistently demonstrated. Understanding the heritability of this resistance will help clarify the nature of population-level responses to chronic exposure to PAH mixtures and aid in identifying the important mechanistic components of resistance to aryl hydrocarbons. We compared the response of Atlantic Wood F1 and F2 embryos to benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and a mixture of BkF and fluoranthene (Fl) to that of F1 embryos of reference site killifish. Resistance to cardiac teratogenesis and induction of CYP mRNA expression and CYP activity was determined. We found that both Atlantic Wood F1 and F2 embryos were highly resistance to cardiac teratogenesis. However, the resistance by Atlantic Wood F2 embryos to induction of CYP mRNA expression and enzyme activity was intermediate between that of Atlantic Wood F1 embryos and reference embryos. These results suggest that resistance to cardiac teratogenesis in Atlantic Wood fish is conferred by multiple factors, not all of which appear to be fully genetically heritable.

  6. Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway

    PubMed Central

    Clark, B. W.; Bone, A. J.; Di Giulio, R. T.

    2014-01-01

    Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Superfund site on the Elizabeth River (Portsmouth, VA, USA) are exposed to a complex mixture of polycyclic aromatic hydrocarbons (PAHs) from former creosote operations, but are resistant to the acute toxicity and cardiac teratogenesis caused by PAHs. The resistance is associated with a dramatic recalcitrance to induction of cytochrome P450 (CYP1) metabolism enzymes following exposure to aryl hydrocarbon receptor (AHR) agonists, along with an elevated antioxidant response and increased expression of several other xenobiotic metabolism and excretion enzymes. However, the heritability of the resistance in the absence of chemical stressors has been inconsistently demonstrated. Understanding the heritability of this resistance will help clarify the nature of population-level responses to chronic exposure to PAH mixtures and aid in identifying the important mechanistic components of resistance to aryl hydrocarbons. We compared the response of Atlantic Wood F1 and F2 embryos to benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), 3,3’,4,4’,5-pentachlorobiphenyl (PCB-126), and a mixture of BkF and fluoranthene (Fl) to that of F1 embryos of reference site killifish. Resistance to cardiac teratogenesis and induction of CYP mRNA expression and CYP activity was determined. We found that both Atlantic Wood F1 and F2 embryos were highly resistance to cardiac teratogenesis. However, the resistance by Atlantic Wood F2 embryos to induction of CYP mRNA expression and enzyme activity was intermediate between that of Atlantic Wood F1 embryos and reference embryos. These results suggest that resistance to cardiac teratogenesis in Atlantic Wood fish is conferred by multiple factors, not all of which appear to be fully genetically heritable. PMID:24374617

  7. Force-activated reactivity switch in a bimolecular chemical reaction.

    PubMed

    Garcia-Manyes, Sergi; Liang, Jian; Szoszkiewicz, Robert; Kuo, Tzu-Ling; Fernández, Julio M

    2009-06-01

    The effect of mechanical force on the free-energy surface that governs a chemical reaction is largely unknown. The combination of protein engineering with single-molecule force-clamp spectroscopy allows us to study the influence of mechanical force on the rate at which a protein disulfide bond is reduced by nucleophiles in a bimolecular substitution reaction (S(N)2). We found that cleavage of a protein disulfide bond by hydroxide anions exhibits an abrupt reactivity 'switch' at ∼500 pN, after which the accelerating effect of force on the rate of an S(N)2 chemical reaction greatly diminishes. We propose that an abrupt force-induced conformational change of the protein disulfide bond shifts its ground state, drastically changing its reactivity in S(N)2 chemical reactions. Our experiments directly demonstrate the action of a force-activated switch in the chemical reactivity of a single molecule.

  8. Active colloids in the context of chemical kinetics

    NASA Astrophysics Data System (ADS)

    Oshanin, G.; Popescu, M. N.; Dietrich, S.

    2017-03-01

    We study a mesoscopic model of a chemically active colloidal particle which on certain parts of its surface promotes chemical reactions in the surrounding solution. For reasons of simplicity and conceptual clarity, we focus on the case in which only electrically neutral species are present in the solution and on chemical reactions which are described by first order kinetics. Within a self-consistent approach we explicitly determine the steady state product and reactant number density fields around the colloid as functionals of the interaction potentials of the various molecular species in solution with the colloid. By using a reciprocal theorem, this allows us to compute and to interpret—in a transparent way in terms of the classical Smoluchowski theory of chemical kinetics—the external force needed to keep such a catalytically active colloid at rest (stall force) or, equivalently, the corresponding velocity of the colloid if it is free to move. We use the particular case of triangular-well interaction potentials as a benchmark example for applying the general theoretical framework developed here. For this latter case, we derive explicit expressions for the dependences of the quantities of interest on the diffusion coefficients of the chemical species, the reaction rate constant, the coverage by catalyst, the size of the colloid, as well as on the parameters of the interaction potentials. These expressions provide a detailed picture of the phenomenology associated with catalytically-active colloids and self-diffusiophoresis.

  9. Grazing-activated chemical defence in a unicellular marine alga

    NASA Astrophysics Data System (ADS)

    Wolfe, Gordon V.; Steinke, Michael; Kirst, Gunter O.

    1997-06-01

    Marine plankton use a variety of defences against predators, some of which affect trophic structure and biogeochemistry. We have previously shown that, during grazing by the protozoan Oxyrrhis marina on the alga Emiliania huxleyi, dimethylsulphoniopropionate (DMSP) from the prey is converted to dimethyl sulphide (DMS) when lysis of ingested prey cells initiates mixing of algal DMSP and the enzyme DMSP lyase. Such a mechanism is similar to macrophyte defence reactions,. Here we show that this reaction deters protozoan herbivores, presumably through the production of highly concentrated acrylate, which has antimicrobial activity. Protozoan predators differ in their ability to ingest and survive on prey with high-activity DMSP lyase, but all grazers preferentially select strains with low enzyme activity when offered prey mixtures. This defence system involves investment in a chemical precursor, DMSP, which is not self-toxic and has other useful metabolic functions. We believe this is the first report of grazing-activated chemical defence in unicellular microorganisms.

  10. AHR2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and PCB-126 in Atlantic killifish (Fundulus heteroclitus).

    PubMed

    Clark, Bryan W; Matson, Cole W; Jung, Dawoon; Di Giulio, Richard T

    2010-08-15

    Exposure of developing fish to polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) results in a suite of defects including cardiac malformation, pericardial and yolk sac edema, craniofacial defects, and hemorrhaging. Several populations of Atlantic killifish or mummichog (Fundulus heteroclitus) on the Atlantic coast of the United States are resistant to the developmental and acute toxicity caused by PAHs and HAHs; this has made Fundulus a valuable model for studying aryl hydrocarbon sensitivity and adaptation. In order to further increase the utility of Fundulus, better understanding of the components of the molecular pathways governing aryl hydrocarbon response in Fundulus is required. The aryl hydrocarbon receptor (AHR) is known to mediate many of the toxic responses to PAHs and HAHs. A single AHR has been identified in mammals, but Fundulus has two AHRs and their relative roles are not clear. In the current study, translation-blocking and splice-junction morpholino gene knockdown was used to determine the roles of AHR1 and AHR2 in mediating cardiac teratogenesis induced by beta-naphthoflavone (BNF), benzo[k]fluoranthene (BkF), and 3,3',4,4',5-pentachlorobiphenyl (PCB-126). Here we report that AHR2 and not AHR1 knockdown resulted in rescue of teratogenicity induced by BNF, BkF, and PCB-126. These data demonstrate that AHR2 is the primary mediator of cardiac teratogenesis caused by multiple aryl hydrocarbons in Fundulus and suggest that suppression of the AHR pathway through modulation of AHR2 is a plausible mechanism for PAH resistance in adapted fish. Additionally, this is the first reported use of splice-junction morpholinos in Fundulus.

  11. Chemical Components and Cardiovascular Activities of Valeriana spp.

    PubMed Central

    Chen, Heng-Wen; Wei, Ben-Jun; He, Xuan-Hui; Liu, Yan; Wang, Jie

    2015-01-01

    Valeriana spp. is a flowering plant that is well known for its essential oils, iridoid compounds such as monoterpenes and sesquiterpenes, flavonoids, alkaloids, amino acids, and lignanoids. Valeriana spp. exhibits a wide range of biological activities such as lowering blood pressure and heart rate, antimyocardial ischemia reperfusion injury, antiarrhythmia, and regulation of blood lipid levels. This review focuses on the chemical constituents and cardiovascular activities of Valeriana spp. PMID:26788113

  12. 75 FR 49550 - Fifth Meeting: RTCA Special Committee 219: Attitude and Heading Reference System (AHRS)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... Federal Aviation Administration Fifth Meeting: RTCA Special Committee 219: Attitude and Heading Reference...: Notice of RTCA Special Committee 219: Attitude and Heading Reference System (AHRS). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of ] RTCA Special Committee 219: Attitude...

  13. RELATIONSHIPS BETWEEN RESIDUES OF AHR AGONISTS IN FISH AND CONCENTRATIONS IN WATER AND SEDIMENTS

    EPA Science Inventory

    Relationships between Residues of AhR Agonists in Fish and Concentrations in Water and Sediment. Cook, PM*, Burkhard, LP, Mount, DR, US-EPA, NHEERL, MED, Duluth, MN. The bioaccumulation visualization approach of Burkhard et al. (2002) can be effectively used to describe the bioa...

  14. EXPRESSION OF AHR AND ARNT MRNA IN CULTURED HUMAN ENDOMETRIAL EXPLANTS EXPOSED TO TCDD

    EPA Science Inventory

    Expression of AhR and ARNT mRNA in cultured human endometrial explants exposed to TCDD.

    Pitt JA, Feng L, Abbott BD, Schmid J, Batt RE, Costich TG, Koury ST, Bofinger DP.

    Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.

    Endom...

  15. Sensitive detection of chemical agents and toxic industrial chemicals using active open-path FTIRs

    NASA Astrophysics Data System (ADS)

    Walter, William T.

    2004-03-01

    Active open-path FTIR sensors provide more sensitive detection of chemical agents than passive FTIRs, such as the M21 RSCAAL and JSLSCAD, and at the same time identify and quantify toxic industrial chemicals (TIC). Passive FTIRs are bistatic sensors relying on infrared sources of opportunity. Utilization of earth-based sources of opportunity limits the source temperatures available for passive chemical-agent FTIR sensors to 300° K. Active FTIR chemical-agent sensors utilize silicon carbide sources, which can be operated at 1500° K. The higher source temperature provides more than an 80-times increase in the infrared radiant flux emitted per unit area in the 7 to 14 micron spectral fingerprint region. Minimum detection limits are better than 5 μgm/m3 for GA, GB, GD, GF and VX. Active FTIR sensors can (1) assist first responders and emergency response teams in their assessment of and reaction to a terrorist threat, (2) provide information on the identification of the TIC present and their concentrations and (3) contribute to the understanding and prevention of debilitating disorders analogous to the Gulf War Syndrome for military and civilian personnel.

  16. Structure activity relationships to assess new chemicals under TSCA

    SciTech Connect

    Auletta, A.E.

    1990-12-31

    Under Section 5 of the Toxic Substances Control Act (TSCA), manufacturers must notify the US Environmental Protection Agency (EPA) 90 days before manufacturing, processing, or importing a new chemical substance. This is referred to as a premanufacture notice (PMN). The PMN must contain certain information including chemical identity, production volume, proposed uses, estimates of exposure and release, and any health or environmental test data that are available to the submitter. Because there is no explicit statutory authority that requires testing of new chemicals prior to their entry into the market, most PMNs are submitted with little or no data. As a result, EPA has developed special techniques for hazard assessment of PMN chemicals. These include (1) evaluation of available data on the chemical itself, (2) evaluation of data on analogues of the PMN, or evaluation of data on metabolites or analogues of metabolites of the PMN, (3) use of quantitative structure activity relationships (QSARs), and (4) knowledge and judgement of scientific assessors in the interpretation and integration of the information developed in the course of the assessment. This approach to evaluating potential hazards of new chemicals is used to identify those that are most in need of addition review of further testing. It should not be viewed as a replacement for testing. 4 tabs.

  17. Gas-Phase Ambient Air Contaminants Exhibit Significant Dioxin-like and Estrogen-like Activity in Vitro

    PubMed Central

    Klein, Gail P.; Hodge, Erin M.; Diamond, Miriam L.; Yip, Amelia; Dann, Tom; Stern, Gary; Denison, Michael S.; Harper, Patricia A.

    2006-01-01

    Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)–based and estrogen receptor (ER)–based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (∑) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10–100 times more abundant than that of ∑polychlorinated biphenyls, ∑nitro-polycyclic aromatic hydrocarbons, and ∑organochlorine pesticides, and 103 to 104 times more abundant than ∑polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways. PMID:16675423

  18. The genome-wide transcriptional response to neonatal hyperoxia identifies Ahr as a key regulator

    PubMed Central

    Bhattacharya, Soumyaroop; Zhou, Zhongyang; Yee, Min; Chu, Chin-Yi; Lopez, Ashley M.; Lunger, Valerie A.; Solleti, Siva Kumar; Resseguie, Emily; Buczynski, Bradley; O'Reilly, Michael A.

    2014-01-01

    Premature infants requiring supplemental oxygen are at increased risk for developing bronchopulmonary dysplasia (BPD). Rodent models involving neonatal exposure to excessive oxygen concentrations (hyperoxia) have helped to identify mechanisms of BPD-associated pathology. Genome-wide assessments of the effects of hyperoxia in neonatal mouse lungs could identify novel BPD-related genes and pathways. Newborn C57BL/6 mice were exposed to 100% oxygen for 10 days, and whole lung tissue RNA was used for high-throughput, sequencing-based transcriptomic analysis (RNA-Seq). Significance Analysis of Microarrays and Ingenuity Pathway Analysis were used to identify genes and pathways affected. Expression patterns for selected genes were validated by qPCR. Mechanistic relationships between genes were further tested in cultured mouse lung epithelial cells. We identified 300 genes significantly and substantially affected following acute neonatal hyperoxia. Canonical pathways dysregulated in hyperoxia lungs included nuclear fctor (erythryoid-derived-2)-like 2-mediated oxidative stress signaling, p53 signaling, eNOS signaling, and aryl hydrocarbon receptor (Ahr) pathways. Cluster analysis identified Ccnd1, Cdkn1a, and Ahr as critical regulatory nodes in the response to hyperoxia, with Ahr serving as the major effector node. A mechanistic role for Ahr was assessed in lung epithelial cells, and we confirmed its ability to regulate the expression of multiple hyperoxia markers, including Cdkn1a, Pdgfrb, and A2m. We conclude that a global assessment of gene regulation in the acute neonatal hyperoxia model of BPD-like pathology has identified Ahr as one driver of gene dysregulation. PMID:25150061

  19. Combining NMR spectral and structural data to form models of polychlorinated dibenzodioxins, dibenzofurans, and biphenyls binding to the AhR

    NASA Astrophysics Data System (ADS)

    Beger, Richard D.; Buzatu, Dan A.; Wilkes, Jon G.

    2002-10-01

    A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, carbon-to-carbon connections, and distances between the carbons. Two-dimensional 13C-13C COSY and 2D slices from the distance dimension of the 3D-connectivity matrix were used to produce a relationship among the 2D spectral patterns for polychlorinated dibenzofurans, dibenzodioxins, and biphenyls (PCDFs, PCDDs, and PCBs respectively) binding to the aryl hydrocarbon receptor (AhR). We refer to this technique as comparative structural connectivity spectral analysis (CoSCoSA) modeling. All CoSCoSA models were developed using forward multiple linear regression analysis of the predicted 13C NMR structure-connectivity spectral bins. A CoSCoSA model for 26 PCDFs had an explained variance (r2) of 0.93 and an average leave-four-out cross-validated variance (q4 2) of 0.89. A CoSCoSA model for 14 PCDDs produced an r2 of 0.90 and an average leave-two-out cross-validated variance (q2 2) of 0.79. One CoSCoSA model for 12 PCBs gave an r2 of 0.91 and an average q2 2 of 0.80. Another CoSCoSA model for all 52 compounds had an r2 of 0.85 and an average q4 2 of 0.52. Major benefits of CoSCoSA modeling include ease of development since the technique does not use molecular docking routines.

  20. Propolis volatile compounds: chemical diversity and biological activity: a review

    PubMed Central

    2014-01-01

    Propolis is a sticky material collected by bees from plants, and used in the hive as building material and defensive substance. It has been popular as a remedy in Europe since ancient times. Nowadays, propolis use in over-the-counter preparations, “bio”-cosmetics and functional foods, etc., increases. Volatile compounds are found in low concentrations in propolis, but their aroma and significant biological activity make them important for propolis characterisation. Propolis is a plant-derived product: its chemical composition depends on the local flora at the site of collection, thus it offers a significant chemical diversity. The role of propolis volatiles in identification of its plant origin is discussed. The available data about chemical composition of propolis volatiles from different geographic regions are reviewed, demonstrating significant chemical variability. The contribution of volatiles and their constituents to the biological activities of propolis is considered. Future perspectives in research on propolis volatiles are outlined, especially in studying activities other than antimicrobial. PMID:24812573

  1. Chemical composition and antimicrobial activity of Polish herbhoneys.

    PubMed

    Isidorov, V A; Bagan, R; Bakier, S; Swiecicka, I

    2015-03-15

    The present study focuses on samples of Polish herbhoneys (HHs), their chemical composition and antimicrobial activity. A gas chromatography-mass spectrometry (GC-MS) method was used to analyse eight samples of herbal honeys and three samples of nectar honeys. Their antimicrobial activities were tested on selected Gram-positive (Bacillus cereus, Staphylococcus aureus, Staphylococcus schleiferi) and Gram-negative (Escherichia coli) bacteria, as well as on pathogenic fungi Candida albicans. Ether extracts of HHs showed significant differences in composition but the principal groups found in the extracts were phenolics and aliphatic hydroxy acids typical of royal jelly and unsaturated dicarboxylic acids. In spite of the differences in chemical composition, antimicrobial activity of the extracts of HHs against all the tested microorganisms except E. coli was observed.

  2. Chemical transformations that yield compounds with distinct activity profiles.

    PubMed

    Hu, Ye; Bajorath, Jürgen

    2011-07-14

    We have systematically searched for chemical changes that generate compounds with distinct biological activity profiles. For this purpose, activity profiles were generated for ∼42000 compounds active against human targets. Unique activity profiles involving multiple target proteins were determined, and all possible matched molecular pairs (MMPs) were identified for compounds representing these profiles. An MMP is defined as a pair of compounds that are distinguished from each other only at a single site such as an R group or ring system. For example, in an MMP, a hydroxyl group might be replaced by a halogen atom or a benzene ring by an amide group. From ∼37500 MMPs, more than 300 nonredundant chemical transformations were isolated that yielded compounds with distinct activity profiles. None of these transformations was found in pairs of compounds with overlapping activity profiles. These transformations were ranked according to the number of MMPs, the number of activity profiles, and the total number of targets that they covered. In many instances, prioritized transformations involved ring systems of varying complexity. All transformations that were found to switch activity profiles are provided to enable further analysis and aid in compound design efforts.

  3. Chemical peels in active acne and acne scars.

    PubMed

    Kontochristopoulos, Georgios; Platsidaki, Eftychia

    Chemical peeling is a widely used procedure in the management of acne and acne scars. It causes controlled destruction of a part of or the entire epidermis, with or without the dermis, leading to exfoliation and removal of superficial lesions, followed by regeneration of new epidermal and dermal tissues. The most frequently used peeling agents are salicylic acid, glycolic acid, pyruvic acid, lactic acid, mandelic acid, Jessner solution, trichloroacetic acid, and phenol. The appropriate peel is chosen based on the patient's skin type, acne activity, and type of acne scars. Combination peels minimize side effects. In acne scars, chemical peels may be combined with other procedures to achieve better clinical results. A series of chemical peels can lead to significant improvement over a short period, leading to patient satisfaction and maintenance of clinical results. © 2016 Elsevier Inc. All rights reserved.

  4. The aryl hydrocarbon receptor suppresses osteoblast proliferation and differentiation through the activation of the ERK signaling pathway

    SciTech Connect

    Yu, Haitao; Du, Yuxuan; Zhang, Xulong; Sun, Ying; Li, Shentao; Dou, Yunpeng; Li, Zhanguo; Yuan, Huihui; Zhao, Wenming

    2014-11-01

    Ahr activation is known to be associated with synovitis and exacerbated rheumatoid arthritis (RA), but its contributions to bone loss have not been completely elucidated. Osteoblast proliferation and differentiation are abnormal at the erosion site in RA. Here, we reported that the expression of Ahr was increased in the hind paws' bone upon collagen-induced arthritis (CIA) in mice, and the levels of Ahr were negatively correlated with bone mineral density (BMD). In addition, immunofluorescent staining showed that the high expression of Ahr was mainly localized in osteoblasts from the CIA mice compared to normal controls. Moreover, the luciferase intensity of Ahr in the nucleus increased by 12.5% in CIA osteoblasts compared to that in normal controls. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activation of the Ahr inhibited pre-osteoblast MC3T3-E1 cellular proliferation and differentiation in a dose-dependent manner. Interestingly, the levels of alkaline phosphatase (ALP) mRNA expression in the osteoblasts of CIA mice were reduced compared to normal controls. In contrast, decreased ALP expression by activated Ahr was completely reversed after pretreatment with an Ahr inhibitor (CH-223191) in MC3T3-E1 cell lines and primary osteoblasts on day 5. Our data further showed that activation of Ahr promoted the phosphorylation of ERK after 5 days. Moreover, Ahr-dependent activation of the ERK signaling pathway decreased the levels of proliferation cells and inhibited ALP activity in MC3T3-E1 cells. These results demonstrated that the high expression of Ahr may suppress osteoblast proliferation and differentiation through activation of the ERK signaling pathway, further enabling bone erosion in CIA mice. - Highlights: • The upregulation of Ahr was localized in osteoblasts of CIA mice. • The overexpression of Ahr suppressed osteoblast development. • The Ahr activated ERK signaling pathway to exacerbate bone erosion.

  5. Dynamics of self-propelled nanomotors in chemically active media

    NASA Astrophysics Data System (ADS)

    Thakur, Snigdha; Kapral, Raymond

    2011-07-01

    Synthetic chemically powered nanomotors often rely on the environment for their fuel supply. The propulsion properties of such motors can be altered if the environment in which they move is chemically active. The dynamical properties of sphere dimer motors, composed of linked catalytic and noncatalytic monomers, are investigated in active media. Chemical reactions occur at the catalytic monomer and the reactant or product of this reaction is involved in cubic autocatalytic or linear reactions that take place in the bulk phase environment. For these reactions, as the bulk phase reaction rates increase, the motor propulsion velocity decreases. For the cubic autocatalytic reaction, this net effect arises from a competition between a reduction of the nonequilibrium concentration gradient that leads to smaller velocity and the generation of fuel in the environment that tends to increase the motor propulsion. The role played by detailed balance in determining the form of the concentration gradient in the motor vicinity in the active medium is studied. Simulations are carried out using reactive multiparticle collision dynamics and compared with theoretical models to obtain further insight into sphere dimer dynamics in active media.

  6. Guiding catalytically active particles with chemically patterned surfaces

    NASA Astrophysics Data System (ADS)

    Uspal, William; Popescu, Mihail; Dietrich, Siegfried; Tasinkevych, Mykola

    Catalytically active Janus particles in solution create gradients in the chemical composition of the solution along their surfaces, as well as along any nearby container walls. The former leads to self-phoresis, while the latter gives rise to chemi-osmosis, providing an additional contribution to self-motility. Chemi-osmosis strongly depends on the molecular interactions between the diffusing chemical species and the wall. We show analytically, using an approximate ``point-particle'' approach, that by chemically patterning a planar substrate (e.g., by adsorbing two different materials) one can direct the motion of Janus particles: the induced chemi-osmotic flows can cause particles to either ``dock'' at a chemical step between the two materials, or to follow a chemical stripe. These theoretical predictions are confirmed by full numerical calculations. Generically, docking occurs for particles which tend to move away from their catalytic caps, while stripe-following occurs in the opposite case. Our analysis reveals the physical mechanisms governing this behavior.

  7. The Search for Endogenous Activators of the Aryl Hydrocarbon Receptor

    PubMed Central

    Nguyen, Linh P.; Bradfield, Christopher A.

    2008-01-01

    In its simplest aspect, this review is an attempt to describe the major ligand classes of the aryl hydrocarbon receptor (AHR). A grander objective is to provide models that may help define the physiological activator or “endogenous ligand” of the AHR. We begin by presenting evidence that supports a developmental function for the AHR. This is followed by proposing mechanisms by which an endogenous ligand and consequent AHR activation might be important during normal physiology and development. With this background, we then present a survey of the known xenobiotic, endogenous, dietary and “un-conventional” activators of the AHR. When possible, this includes information about their induction potency, receptor binding affinity and potential for exposure. Because of the essential function of the AHR in embryonic development, we discuss the candidacy of each of these compounds as physiologically important activators. PMID:18076143

  8. Mining Chemical Activity Status from High-Throughput Screening Assays.

    PubMed

    Soufan, Othman; Ba-alawi, Wail; Afeef, Moataz; Essack, Magbubah; Rodionov, Valentin; Kalnis, Panos; Bajic, Vladimir B

    2015-01-01

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.

  9. Mining Chemical Activity Status from High-Throughput Screening Assays

    PubMed Central

    Soufan, Othman; Ba-alawi, Wail; Afeef, Moataz; Essack, Magbubah; Rodionov, Valentin; Kalnis, Panos; Bajic, Vladimir B.

    2015-01-01

    High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare. PMID:26658480

  10. Promoter analysis of TCDD-inducible genes in a thymic epithelial cell line indicates the potential for cell-specific transcription factor crosstalk in the AhR response

    SciTech Connect

    Frericks, Markus; Burgoon, Lyle D.; Zacharewski, Timothy R.; Esser, Charlotte

    2008-10-15

    Activation of the aryl hydrocarbon receptor (AhR{sup 1}) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elicits severe immunosuppression accompanied by thymic atrophy. Previous evidence suggests that TCDD targets both thymocytes and thymic epithelial cells. The AhR induces cell-specific changes in gene transcription via binding to the dioxin response element DRE; however, the underlying specificity-mechanisms, in particular with regard to the role of promoter element context, and possible transcription factor crosstalk remain poorly understood. Global gene expression in the cortical thymic epithelial cell line ET at 2, 4, and 6 h following 5 nM TCDD exposure resulted in differential regulation of 201 genes. JASPAR and TRANSFAC mapped the statistically over-represented promoter elements in the regulated genes to specific transcription factor binding sites, suggesting a regulatory role in AhR signaling. Over-represented elements included the xenobiotic response element XRE, NF{kappa}B-Rel, HRE, PPAR{gamma}, GR, PAX-4 and estrogen receptor binding sites. Co-treatment experiments with TCDD and CoCl{sub 2}, to induce hypoxia, or TCDD and 17-{beta}-estradiol (E2) indicated crosstalk between AhR and Hif or ER, in agreement with other experimental models. The computational identification of TFBS and the demonstration of interaction confirm their interactions with AhR signaling and suggest that the other over-represented elements may also be important in the immunosuppressive effects elicited by TCDD. In conclusion, we demonstrated the importance of promoter element cooperation in the shaping of a cell-specific AhR response. Our findings regarding the transcriptional changes in cortical epithelial cells are congruent with the well-known thymotoxic TCDD-phenotype, and useful in new hypothesis generation of the role of cortical TECs in TCDD toxicity.

  11. Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

    2002-02-01

    Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

  12. Constitutive Activation of the Aromatic Hydrocarbon Receptor

    PubMed Central

    Chang, Ching-Yi; Puga, Alvaro

    1998-01-01

    The ligand-activated aromatic hydrocarbon receptor (AHR) dimerizes with the AHR nuclear translocator (ARNT) to form a functional complex that transactivates expression of the cytochrome P-450 CYP1A1 gene and other genes in the dioxin-inducible [Ah] gene battery. Previous work from this laboratory has shown that the activity of the CYP1A1 enzyme negatively regulates this process. To study the relationship between CYP1A1 activity and Ah receptor activation we used CYP1A1-deficient mouse hepatoma c37 cells and CYP1A1- and AHR-deficient African green monkey kidney CV-1 cells. Using gel mobility shift and luciferase reporter gene expression assays, we found that c37 cells that had not been exposed to exogenous Ah receptor ligands already contained transcriptionally active AHR-ARNT complexes, a finding that we also observed in wild-type Hepa-1 cells treated with Ellipticine, a CYP1A1 inhibitor. In CV-1 cells, transient expression of AHR and ARNT leads to high levels of AHR–ARNT-dependent luciferase gene expression even in the absence of an agonist. Using a green fluorescent protein-tagged AHR, we showed that elevated reporter gene expression correlates with constitutive nuclear localization of the AHR. Transcriptional activation of the luciferase reporter gene observed in CV-1 cells is significantly decreased by (i) expression of a functional CYP1A1 enzyme, (ii) competition with chimeric or truncated AHR proteins containing the AHR ligand-binding domain, and (iii) treatment with the AHR antagonist α-naphthoflavone. These results suggest that a CYP1A1 substrate, which accumulates in cells lacking CYP1A1 enzymatic activity, is an AHR ligand responsible for endogenous activation of the Ah receptor. PMID:9418899

  13. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  14. Chemical reactivity and antimicrobial activity of N-substituted maleimides.

    PubMed

    Salewska, Natalia; Boros-Majewska, Joanna; Lącka, Izabela; Chylińska, Katarzyna; Sabisz, Michał; Milewski, Sławomir; Milewska, Maria J

    2012-02-01

    Several N-substituted maleimides containing substituents of varying bulkiness and polarity were synthesised and tested for antimicrobial and cytostatic activity. Neutral maleimides displayed relatively strong antifungal effect minimum inhibitory concentrations (MICs in the 0.5-4 µg ml(-1) range); their antibacterial activity was structure dependent and all were highly cytostatic, with IC(50) values below 0.1 µg ml(-1). Low antimicrobial but high cytostatic activity was noted for basic maleimides containing tertiary aminoalkyl substituents. Chemical reactivity and lipophilicity influenced antibacterial activity of neutral maleimides but had little if any effect on their antifungal and cytostatic action. N-substituted maleimides affected biosynthesis of chitin and β(1,3)glucan, components of the fungal cell wall. The membrane enzyme, β(1,3)glucan synthase has been proposed as a putative primary target of N-ethylmaleimide and some of its analogues in Candida albicans cells.

  15. Active hydrothermal and non-active massive sulfide mound investigation using a new multiparameter chemical sensor

    NASA Astrophysics Data System (ADS)

    Han, C.; Wu, G.; Qin, H.; Wang, Z.

    2012-12-01

    Investigation of active hydrothermal mound as well as non-active massive sulfide mound are studied recently. However, there is still lack of in-situ detection method for the non-active massive sulfide mound. Even though Transient ElectroMagnetic (TEM) and Electric Self-potential (SP) methods are good, they both are labour, time and money cost work. We proposed a new multiparameter chemical sensor method to study the seafloor active hydrothermal mound as well as non-active massive sulfide mound. This sensor integrates Eh, S2- ions concentration and pH electrochemical electrodes together, and could found chemical change caused by the active hydrothermal vent, even weak chemical abnormalities by non-active massive sulfide hydrothermal mound which MARP and CTD sometimes cannot detect. In 2012, the 1st Leg of the Chinese 26th cruise, the multiparameter chemical sensor was carried out with the deepsea camera system over the Carlsberg Ridge in Indian Ocean by R/V DAYANGYIHAO. It was shown small Eh and S2- ions concentration abnormal around a site at Northwest Indian ridge. This site was also evidenced by the TV grab. In the 2nd Leg of the same cruise in June, this chemical sensor was carried out with TEM and SP survey system. The chemical abnormalities are matched very well with both TEM and SP survey results. The results show that the multiparameter chemical sensor method not only can detect active hydrothermal mound, but also can find the non-active massive sulfide hydrothermal mound.

  16. Characterization testing of a 40 AHR bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Brewer, Jeffrey C.; Manzo, Michelle A.; Gemeiner, Russel P.

    1989-01-01

    Extensive characterization testing has been done on a second 40 amp-hour (Ahr), 10-cell bipolar nickel-hydrogen (Ni-H2) battery to study the effects of such operating parameters as charge and discharge rates, temperature, and pressure, on capacity, Ahr and watt-hour (Whr) efficiencies, end-of-charge (EOC) and mid-point discharge voltages. Testing to date has produced many interesting results, with the battery performing well throughout all of the test matrix except during the high-rate (5C and 10C) discharges, where poorer than expected results were observed. The exact cause of this poor performance is, as yet, unknown. Small scale 2 x 2 inch battery tests are to be used in studying this problem. Low earth orbit (LEO) cycle life testing at a 40 percent depth of discharge (DOD) and 10 C is scheduled to follow the characterization testing.

  17. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach.

    PubMed Central

    Safe, S H

    1998-01-01

    There is considerable public, regulatory, and scientific concern regarding human exposure to endocrine-disrupting chemicals, which include compounds that directly modulate steroid hormone receptor pathways (estrogens, antiestrogens, androgens, antiandrogens) and aryl hydrocarbon receptor (AhR) agonists, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Based on quantitative structure-activity relationships for both AhR and estrogen receptor (ER) agonists, the relative potency (RP) of individual compounds relative to a standard (e.g. TCDD and 17-beta-estradiol) have been determined for several receptor-mediated responses. Therefore, the TCDD or estrogenic equivalent (TEQ or EQ, respectively) of a mixture is defined as TEQ = sigma[T(i)]xRP(i)or EQ=sigma[E(i)]xRP(i), where T(i) and E(i) are concentrations of individual AhR or ER agonists in any mixture. This approach for risk assessment of endocrine-disrupting mixtures assumes that for each endocrine response pathway, the effects of individual compounds are essentially additive. This paper will critically examine the utility of the TEQ/EQ approach for risk assessment, the validity of the assumptions used for this approach, and the problems associated with comparing low dose exposures to xeno and natural (dietary) endocrine disruptors. PMID:9703492

  18. Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas.

    PubMed

    Cannavo, S; Ragonese, M; Puglisi, S; Romeo, P D; Torre, M L; Alibrandi, A; Scaroni, C; Occhi, G; Ceccato, F; Regazzo, D; De Menis, E; Sartorato, P; Arnaldi, G; Trementino, L; Trimarchi, F; Ferrau, F

    2016-04-01

    In this multicentric study, we aimed to correlate the occurrence of AHR and/or AIP. genes variants in acromegalic patients with the disease severity and/or with the response to somatostatin analogs (SSa) treatment, according to pollution exposition.

  19. Aryl hydrocarbon receptor mediates both proinflammatory and anti-inflammatory effects in lipopolysaccharide-activated microglia.

    PubMed

    Lee, Yi-Hsuan; Lin, Chun-Hua; Hsu, Pei-Chien; Sun, Yu-Yo; Huang, Yu-Jie; Zhuo, Jiun-Horng; Wang, Chen-Yu; Gan, Yu-Ling; Hung, Chia-Chi; Kuan, Chia-Yi; Shie, Feng-Shiun

    2015-07-01

    The aryl hydrocarbon receptor (AhR) regulates peripheral immunity; but its role in microglia-mediated neuroinflammation in the brain remains unknown. Here, we demonstrate that AhR mediates both anti-inflammatory and proinflammatory effects in lipopolysaccharide (LPS)-activated microglia. Activation of AhR by its ligands, formylindolo[3,2-b]carbazole (FICZ) or 3-methylcholanthrene (3MC), attenuated LPS-induced microglial immune responses. AhR also showed proinflammatory effects, as evidenced by the findings that genetic silence of AhR ameliorated the LPS-induced microglial immune responses and LPS-activated microglia-mediated neurotoxicity. Similarly, LPS-induced expressions of tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) were reduced in the cerebral cortex of AhR-deficient mice. Intriguingly, LPS upregulated and activated AhR in the absence of AhR ligands via the MEK1/2 signaling pathway, which effects were associated with a transient inhibition of cytochrome P450 1A1 (CYP1A1). Although AhR ligands synergistically enhance LPS-induced AhR activation, leading to suppression of LPS-induced microglial immune responses, they cannot do so on their own in microglia. Chromatin immunoprecipitation results further revealed that LPS-FICZ co-treatment, but not LPS alone, not only resulted in co-recruitment of both AhR and NFκB onto the κB site of TNFα gene promoter but also reduced LPS-induced AhR binding to the DRE site of iNOS gene promoter. Together, we provide evidence showing that microglial AhR, which can be activated by LPS, exerts bi-directional effects on the regulation of LPS-induced neuroinflammation, depending on the availability of external AhR ligands. These findings confer further insights into the potential link between environmental factors and the inflammatory brain disorders.

  20. Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities.

    PubMed

    Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

    2016-09-03

    The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

  1. Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

    PubMed Central

    Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

    2016-01-01

    The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression. PMID:27598154

  2. Resveratrol and its methoxy derivatives modulate the expression of estrogen metabolism enzymes in breast epithelial cells by AhR down-regulation.

    PubMed

    Licznerska, Barbara; Szaefer, Hanna; Wierzchowski, Marcin; Sobierajska, Hanna; Baer-Dubowska, Wanda

    2017-01-01

    Our earlier studies have shown that compared to resveratrol, its analogs with ortho-methoxy substituents exert stronger antiproliferative and proapoptotic activity. Since estrogens are considered the major risk factors of breast carcinogenesis, the aim of this study was to evaluate the effect of 3,4,2'-trimethoxy (3MS), 3,4,2',4'-tetramethoxy (4MS), and 3,4,2',4',6'-pentamethoxy (5MS) trans-stilbenes on the constitutive expression of the enzymes involved in estrogen metabolism, as well as receptors: AhR and HER2 in breast epithelial cell line MCF10A. The results showed different effect of resveratrol and its methoxy derivatives on the expression of genes encoding key enzymes of estrogen synthesis and catabolism. Resveratrol at the doses of 1 and 5 µmol/L increased the level of CYP19 transcript and protein level, while 5MS reduced mRNA transcript of both CYP19 and STS genes. Resveratrol and all its derivatives reduced also SULT1E1 mRNA transcript level. The reduced expression of AhR, CYP1A1, and 1B1 was also found as a result of treatment with these compounds. The most significant changes were found in the case of AhR. The most potent inhibitor of CYP1A1 and 1B1 genes expression was 5MS, which reduced the levels of mRNA transcript and protein of both CYPs from 31 to 89% of the initial levels. These results indicate that methoxy derivatives of resveratrol might be efficient modulators of estrogen metabolism. Moreover, the number of methoxy groups introduced to stilbene structure may play a certain role in this effect.

  3. Chemical Signaling and Functional Activation in Colloidosome-Based Protocells.

    PubMed

    Sun, Shiyong; Li, Mei; Dong, Faqin; Wang, Shengjie; Tian, Liangfei; Mann, Stephen

    2016-04-13

    An aqueous-based microcompartmentalized model involving the integration of partially hydrophobic Fe(III)-rich montmorillonite (FeM) clay particles as structural and catalytic building blocks for colloidosome membrane assembly, self-directed membrane remodeling, and signal-induced protocell communication is described. The clay colloidosomes exhibit size- and charge-selective permeability, and show dual catalytic functions involving spatially confined enzyme-mediated dephosphorylation and peroxidase-like membrane activity. The latter is used for the colloidosome-mediated synthesis and assembly of a temperature-responsive poly(N-isopropylacrylamide)(PNIPAM)/clay-integrated hybrid membrane. In situ PNIPAM elaboration of the membrane is coupled to a glucose oxidase (GOx)-mediated signaling pathway to establish a primitive model of chemical communication and functional activation within a synthetic "protocell community" comprising a mixed population of GOx-containing silica colloidosomes and alkaline phosphatase (ALP)-containing FeM-clay colloidosomes. Triggering the enzyme reaction in the silica colloidosomes gives a hydrogen peroxide signal that induces polymer wall formation in a coexistent population of the FeM-clay colloidosomes, which in turn generates self-regulated membrane-gated ALP-activity within the clay microcompartments. The emergence of new functionalities in inorganic colloidosomes via chemical communication between different protocell populations provides a first step toward the realization of interacting communities of synthetic functional microcompartments.

  4. Atypical Hydrogen Uptake on Chemically Activated, Ultramicroporous Carbon

    SciTech Connect

    Bhat, Vinay V; Contescu, Cristian I; Gallego, Nidia C; Baker, Frederick S

    2010-01-01

    Hydrogen adsorption at near-ambient temperatures on ultramicroporous carbon (UMC), derived through secondary chemical activation from a wood-based activated carbon was studied using volumetric and gravimetric methods. The results showed that physisorption is accompanied by a process of different nature that causes slow uptake at high pressures and hysteresis on desorption. In combination, this results in unusually high levels of hydrogen uptake at near-ambient temperatures and pressures (e.g. up to 0.8 wt % at 25 oC and 2 MPa). The heat of adsorption corresponding to the slow process leading to high uptake (17 20 kJ/mol) is higher than usually reported for carbon materials, but the adsorption kinetics is slow, and the isotherms exhibit pronounced hysteresis. These unusual properties were attributed to contributions from polarization-enhanced physisorption caused by traces of alkali metals residual from chemical activation. The results support the hypothesis that polarization-induced physisorption in high surface area carbons modified with traces of alkali metal ions is an alternate route for increasing the hydrogen storage capacity of carbon adsorbents.

  5. An Assessment of Technical and Production Risks of Candidate Low-Cost Attitude/Heading Reference Systems(AHRS)

    NASA Technical Reports Server (NTRS)

    Yuchnovicz, Daniel; Burgess, Malcolm; Hammers, William

    1999-01-01

    This report provides an assessment of technical and production risks of candidate low-cost attitude/heading reference systems (AHRS) for use in the Advanced General Aviation Transport Experiments (AGATE) airplanes. A low-cost AHRS is a key component of modem "glass cockpit" flight displays for General Aviation (GA) aircraft. The technical capabilities of several candidate low-cost AHRS were examined and described along with the technical issues involved with using all solid-state components for attitude measurement. An economic model was developed which describes the expected profit, rate of return, and volume requirements for the manufacture of low-cost AHRS for GA aircraft in the 2000 to 2020 time frame. The model is the result of interviews with GA airframe manufacturers, avionics manufacturers and historical analysis of avionics of similar complexity. The model shows that a manufacturer will break even after three years of AHRS production, realizing an 18 percent rate of return (23 percent profit) on an investment of $3.5M over the 20 year period. A start-up production estimate showed costs of $6-12M for a new company to build and certify an AHRS from scratch, considered to be a high-risk proposition, versus $0.25-0.75M for an experienced avionics manufacturer to manufacture a design under license, a low-risk proposition.

  6. Regular Wave Propagation Out of Noise in Chemical Active Media

    SciTech Connect

    Alonso, S.; Sendina-Nadal, I.; Perez-Munuzuri, V.; Sancho, J. M.; Sagues, F.

    2001-08-13

    A pacemaker, regularly emitting chemical waves, is created out of noise when an excitable photosensitive Belousov-Zhabotinsky medium, strictly unable to autonomously initiate autowaves, is forced with a spatiotemporal patterned random illumination. These experimental observations are also reproduced numerically by using a set of reaction-diffusion equations for an activator-inhibitor model, and further analytically interpreted in terms of genuine coupling effects arising from parametric fluctuations. Within the same framework we also address situations of noise-sustained propagation in subexcitable media.

  7. Regular wave propagation out of noise in chemical active media.

    PubMed

    Alonso, S; Sendiña-Nadal, I; Pérez-Muñuzuri, V; Sancho, J M; Sagués, F

    2001-08-13

    A pacemaker, regularly emitting chemical waves, is created out of noise when an excitable photosensitive Belousov-Zhabotinsky medium, strictly unable to autonomously initiate autowaves, is forced with a spatiotemporal patterned random illumination. These experimental observations are also reproduced numerically by using a set of reaction-diffusion equations for an activator-inhibitor model, and further analytically interpreted in terms of genuine coupling effects arising from parametric fluctuations. Within the same framework we also address situations of noise-sustained propagation in subexcitable media.

  8. Genotoxic activity of organic chemicals in drinking water.

    PubMed

    Meier, J R

    1988-11-01

    The information summarized in this review provides substantial evidence for the widespread presence of genotoxins in drinking water. In many, if not most cases, the genotoxic activity can be directly attributed to the chlorination stage of drinking water treatment. The genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Genotoxic activity in drinking water concentrates has been most frequently demonstrated using bacterial mutagenicity tests but results with mammalian cell assay systems are generally consistent with the findings from the bacterial assays. There is currently no evidence for genotoxic damage following in vivo exposures to animals. In some locations genotoxic contaminants of probable industrial and/or agricultural origin occur in the source waters and contribute substantially to the genotoxic activity of finished drinking waters. The method used for sample concentration can have an important bearing on study results. In particular, organic acids account for most of the mutagenicity of chlorinated drinking water, and their recovery from water requires a sample acidification step prior to extraction or XAD resin adsorption. Considerable work has been done to determine the identity of the compounds responsible for the mutagenicity of organic concentrates of drinking water. Recently, one class of acidic compounds, the chlorinated hydroxyfuranones, has been shown to be responsible for a major part of the mutagenic activity. Strategies for drinking water treatment that have been evaluated with respect to reduction of genotoxins in drinking water include granular activated carbon (GAC) filtration, chemical destruction, and the use of alternative means of treatment (i.e., ozone, chlorine dioxide, and monochloramine). GAC treatment has been found to be effective for removal of mutagens from drinking water even after the GAC is beyond its normal use for organic carbon removal. All disinfectant

  9. Fate of steroid hormones and endocrine activities in swine manure disposal and treatment facilities.

    PubMed

    Combalbert, Sarah; Bellet, Virginie; Dabert, Patrick; Bernet, Nicolas; Balaguer, Patrick; Hernandez-Raquet, Guillermina

    2012-03-01

    Manure may contain high concern endocrine-disrupting compounds (EDCs) such as steroid hormones, naturally produced by pigs, which are present at μgL(-1) levels. Manure may also contain other EDCs such as nonylphenols (NP), polycyclic aromatic hydrocarbons (PAHs) and dioxins. Thus, once manure is applied to the land as soil fertilizer these compounds may reach aquifers and consequently living organisms, inducing abnormal endocrine responses. In France, manure is generally stored in anaerobic tanks prior spreading on land; when nitrogen removal is requested, manure is treated by aerobic processes before spreading. However, little is known about the fate of hormones and multiple endocrine-disrupting activities in such manure disposal and treatment systems. Here, we determined the fate of hormones and diverse endocrine activities during manure storage and treatment by combining chemical analysis and in vitro quantification of estrogen (ER), aryl hydrocarbon (AhR), androgen (AR), pregnane-X (PXR) and peroxysome proliferator-activated γ (PPARγ) receptor-mediated activities. Our results show that manure contains large quantities of hormones and activates ER and AhR, two of the nuclear receptors studied. Most of these endocrine activities were found in the solid fraction of manure and appeared to be induced mainly by hormones and other unidentified pollutants. Hormones, ER and AhR activities found in manure were poorly removed during manure storage but were efficiently removed by aerobic treatment of manure.

  10. Halloysite clay nanotubes for controlled delivery of chemically active agents

    NASA Astrophysics Data System (ADS)

    Abdullayev, Elshard

    In this work we explored the capabilities of halloysite nanotubes as capsules for encapsulation and controlled delivery of the chemically and biologically active substances. Halloysite is a two-layered aluminosilicate which has a predominantly hollow tubular structure in the submicron range and is chemically similar to kaolinite [1, 2]. In the first section of this work, we analyzed the structure of the halloysite nanotubes as well as its capability to encapsulate and deliver biologically and chemically active agents, similarities and differences between release characteristics of different agents and how these differences relate with their chemical structure. Models were used to describe the release characteristics of the active agents. Study of the interaction between loaded agents and halloysite nanotubes provides better understanding of the release characteristics of the loaded agents and how halloysite can be implemented for technological and medical applications. The second part of the work deals with self-healing coatings produced on the basis of halloysite nanotubes loaded with corrosion inhibitors. Self-healing coatings are one of the effective methods to protect metals from corrosion and deterioration. The difference between self-healing coatings and the usual coatings is the ability of the first to recover after the formation of the damages due to external or internal stresses. High efficiency of the self- healing coatings produced by halloysite nanotubes were demonstrated on 110 Copper alloys and 2024 aluminum alloys. Controlled delivery of the corrosion inhibitors with additional encapsulation of the halloysite nanotubes by synthesizing stoppers at tube endings was also demonstrated. Additional encapsulation of the halloysite nanotubes may be necessary when slow release of the loaded agents is required or rapid convection of the liquid in the surrounding environment takes place (since this may cause rapid release of the loaded agents without additional

  11. Active membrane having uniform physico-chemically functionalized ion channels

    DOEpatents

    Gerald, II, Rex E; Ruscic, Katarina J; Sears, Devin N; Smith, Luis J; Klingler, Robert J; Rathke, Jerome W

    2012-09-24

    The present invention relates to a physicochemically-active porous membrane for electrochemical cells that purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. One dimension of the pore surface has a macroscopic length (1 nm-1000 .mu.m) and is directed parallel to the direction of an electric field, which is produced between the cathode and the anode electrodes of an electrochemical cell. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

  12. Chemical composition and biological activity of Salvia verbenaca essential oil.

    PubMed

    Canzoneri, Marisa; Bruno, Maurizio; Rosselli, Sergio; Russo, Alessandra; Cardile, Venera; Formisano, Carmen; Rigano, Daniela; Senatore, Felice

    2011-07-01

    Salvia verbenaca L. (syn. S. minore) is a perennial herb known in the traditional medicine of Sicily as "spaccapetri" and is used to resolve cases of kidney stones, chewing the fresh leaves or in decoction. The chemical composition of the essential oil obtained from aerial parts of S. verbenaca collected in Piano Battaglia (Sicily) on July 2009, was analyzed by GC and GC-MS. The oil was strongly characterized by fatty acids (39.5%) and carbonylic compounds (21.2%), with hexadecanoic acid (23.1%), (Z)-9-octadecenoic acid (11.1%) and benzaldehyde (7.3%) as the main constituents. The in vitro activity of the essential oil against some microorganisms in comparison with chloramphenicol by the broth dilution method was determined. The oil exhibited a good activity as inhibitor of growth of Gram + bacteria.

  13. Convective self-propulsion of chemically active particles

    NASA Astrophysics Data System (ADS)

    Shklyaev, Oleg; Shum, Henry; Balazs, Anna

    2016-11-01

    A mechanism of particle self-propulsion activated by transduction of chemical energy into convective motion of fluid that drags microscale particles is proposed. The convection is generated by an active spherical particle located on the bottom of a microchannel and coated with a catalyst that decomposes reagent dissolved in the solution into less dense products and gives rise to a buoyancy force. The symmetry of the flow generated around the active particle can be broken if a passive spherical particle, which does not produce the flow, is present in the vicinity of the first one. The generated flow drags the passive particle toward the active one along the bottom wall until they form a dimer. The resulting asymmetric fluid flow, which is generated by only one of the particles, imposes a different drag on the different sides on the dimer. The net force causes the dimer to translate along the bottom wall. By varying numbers of active and passive particles, as well as their positions within a group, one can control the structure of the generated convective flow and, therefore, design clusters with different mobile properties. The proposed mechanism can be harnessed to transport cargo in microchannels.

  14. Aryl hydrocarbon receptor activity modulates prolactin expression in the pituitary

    PubMed Central

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T.

    2012-01-01

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotroph and lactotroph adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somato-lactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggests environmental dioxins can exert endocrine disrupting effects at the pituitary. PMID:22975028

  15. Influences of chemical activators on incinerator bottom ash

    SciTech Connect

    Qiao, X.C. Cheeseman, C.R.; Poon, C.S.

    2009-02-15

    This research has applied different chemical activators to mechanically and thermally treated fine fraction (<14 mm) of incinerator bottom ash (IBA), in order to investigate the influences of chemical activators on this new pozzolanic material. IBA has been milled and thermally treated at 800 deg. C (TIBA). The TIBA produced was blended with Ca(OH){sub 2} and evaluated for setting time, reactivity and compressive strength after the addition of 0.0565 mole of Na{sub 2}SO{sub 4}, K{sub 2}SO{sub 4}, Na{sub 2}CO{sub 3}, K{sub 2}CO{sub 3}, NaOH, KOH and CaCl{sub 2} into 100 g of binder (TIBA+Ca(OH){sub 2}). The microstructures of activated IBA and hydrated samples have been characterized by X-ray diffraction (XRD) and thermogravimetry (TG) analysis. Thermal treatment is found to produce gehlenite (Ca{sub 2}Al{sub 2}SiO{sub 7}), wollastonite (CaSiO{sub 3}) and mayenite (Ca{sub 12}Al{sub 14}O{sub 33}) phases. The thermally treated IBA samples are significantly more reactive than the milled IBA. The addition of Na{sub 2}CO{sub 3} can increase the compressive strength and calcium hydroxide consumption at 28-day curing ages. However, the addition of Na{sub 2}SO{sub 4}, K{sub 2}SO{sub 4}, K{sub 2}CO{sub 3}, NaOH and KOH reduces the strength and hydration reaction. Moreover, these chemicals produce more porous samples due to increased generation of hydrogen gas. The addition of CaCl{sub 2} has a negative effect on the hydration of TIBA samples. Calcium aluminium oxide carbonate sulphide hydrate (Ca{sub 4}Al{sub 2}O{sub 6}(CO{sub 3}){sub 0.67}(SO{sub 3}){sub 0.33}(H{sub 2}O){sub 11}) is the main hydration product in the samples with activated IBA, except for the sample containing CaCl{sub 2}.

  16. Biological activities and chemical composition of lichens from Serbia

    PubMed Central

    Kosanic, Marijana; Rankovic, Branislav; Stanojkovic, Tatjana; Vasiljevic, Perica; Manojlovic, Nedeljko

    2014-01-01

    The aim of this study is to investigate chemical composition of acetone extracts of the lichens Parmelia arseneana and Acarospora fuscata and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and gyrophoric acid isolated from A. fuscata. The HPLC-UV method was used for the identification of secondary metabolites. Stictic acid, norstictic acid, gyrophoric acid, usnic acid, atranorin and chloroatranorin were identified in the A. fuscata. In P. arseneana, we detected stictic acid, norstictic acid, usnic acid and atranorin, while gyrophoric acid was not identified. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic compounds in extracts. As a result of the study, gyrophoric acid was found to have the largest DPPH radical scavenging activity with an IC50 value of 105.75 µg/ml. Moreover, the tested samples had an effective superoxide anion radical scavenging and reducing power. The total content of phenol in extracts was determined as pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was also gyrophoric acid, with minimum inhibitory concentration values ranging from 0.019 to 1.25 mg/ml. Anticancer activity was tested against LS174 (human colon carcinoma cell line), A549 (human lung carcinoma cell line), Fem-x (malignant melanoma cell line), and a chronic myelogeneous leukaemia K562 cell line using the MTT method. Extract of P. arseneana expressed the strongest anticancer activity against all cell lines with IC50 values ranging from 11.61 to 47.06 µg/ml. PMID:26417336

  17. Speciation and chemical activities in superheated sodium borate solutions

    SciTech Connect

    Weres, O. )

    1993-06-01

    The system H[sub 2]O-B[sub 2]O[sub 3]-Na[sub 2]O has been studied experimentally at 277[degrees] and 317[degrees]C. The activities of water and boric acid have been determined at mole ratios Na/B from 0 to 1.5, and total dissolved solids 3 to 80 weight percent. The activity of boric acid has been fitted to within experimental error using a speciation model with eight complex species. This model is consistent with the model previously published by Mesmer et al. The electrolyte properties of the liquid are modelled using the Pitzer-Simonson Model of very concentrated electrolyte solutions. The calculated values of water activity agree with experiment, and the activity of NaOH and pOH have also been calculated. These data will allow prediction of the composition and chemical behavior of sodium borate liquids that may accumulate in the superheated crevices within a steam generator. A modified form of the model is provided for use with MULTEQ. The potassium borate system also was briefly studied at 317[degrees]C, and is adequately described by a model with five complex species. The potassium borate liquid is more alkaline at K/B = 1 than a sodium borate liquid at the same mole ratio, but pOH in the two systems is the same at lower mole ratios.

  18. Activation of the aryl hydrocarbon receptor pathway enhances cancer cell invasion by upregulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer.

    PubMed

    Ishida, Masaru; Mikami, Shuji; Kikuchi, Eiji; Kosaka, Takeo; Miyajima, Akira; Nakagawa, Ken; Mukai, Makio; Okada, Yasunori; Oya, Mototsugu

    2010-02-01

    Aryl hydrocarbon receptor (AhR) and the activation of the AhR pathway are involved in xenobiotic-induced toxicity and carcinogenesis. Although xenobiotics, such as cigarette smoke, contribute to the development of urothelial carcinoma (UC), the relationship between AhR and UC is unclear. In the present study, we investigated AhR expression in 209 patients with upper urinary tract UC. The nuclear expression of AhR was significantly associated with histological grade, pathological T stage, lymphovascular invasion and lymph node involvement. A multivariate Cox analysis revealed that nuclear AhR expression was a significant and independent predictor for disease-specific survival (hazard ratio = 2.469, P = 0.013). To determine whether the AhR pathway can be activated in the T24 UC cell line, we examined the expression of cytochrome P450 (CYP) 1A1 and CYP1B1, which are target genes of the AhR pathway, following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR. TCDD treatment upregulated the expression levels of AhR, CYP1A1 and CYP1B1. TCDD enhanced T24 cell invasion associated with the upregulation of matrix metalloproteinase (MMP)-1 and MMP-9. Furthermore, targeting AhR messenger RNA (mRNA) expression in T24 cells with small interfering RNA (siRNA) downregulated the mRNA expression of AhR, CYP1A1, CYP1B1, MMP-1, MMP-2 and MMP-9; furthermore, the cells transfected with siRNA for AhR showed decreased invasion activity in comparison with the cells transfected with a non-targeting siRNA. Our results therefore suggest that AhR plays a role in the invasiveness of UC cells and can serve as a marker for the prognosis of upper urinary tract UC.

  19. Wound Healing Activity and Chemical Standardization of Eugenia pruniformis Cambess

    PubMed Central

    de Albuquerque, Ricardo Diego Duarte Galhardo; Perini, Jamila Alessandra; Machado, Daniel Escorsim; Angeli-Gamba, Thaís; Esteves, Ricardo dos Santos; Santos, Marcelo Guerra; Oliveira, Adriana Passos; Rocha, Leandro

    2016-01-01

    Background: Eugenia pruniformis is an endemic species from Brazil. Eugenia genus has flavonoids as one of the remarkable chemical classes which are related to the improvement of the healing process. Aims: To evaluate of wound healing activity of E. pruniformis leaves and to identify and quantify its main flavonoids compounds. Materials And Methods: Wound excision model in rats was used to verify the hydroethanolic and ethyl acetate extracts potential. The animals were divided in four groups of six and the samples were evaluated until the 15° day of treatment. Hydroxyproline dosage and histological staining with hematoxilin-eosin and Sirius Red were used to observe the tissue organization and quantify the collagen deposition, respectively. Chemical compounds of the ethyl acetate extract were identified by chromatographic techniques and mass spectrometry analysis and total flavonoids content was determined by spectrophotometric method. The antioxidant activity was determined by oxygen radical absorbing capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazylhydrate radical photometric (DPPH) assays. Results: The treated group with the ethyl acetate extract showed collagen deposition increase, higher levels of hidroxyproline, better tissue reorganization and complete remodeling of epidermis. Quercetin, kaempferol and hyperoside were identified as main compounds and flavonoids content value was 43% (w/w). The ORAC value of the ethyl acetate extract was 0.81± 0.05 mmol TE/g whereas the concentration to produce 50% reduction of the DPPH was 7.05± 0.09 μg/mL. Conclusion: The data indicate a wound healing and antioxidant activities of E. pruniformis. This study is the first report of flavonoids and wound healing activity of E. pruniformis. KEY MESSAGES Eugenia pruniformis extract accelerates wound healing in skin rat model, probably due to its involvement with the collagen deposition increase, higher levels of hidroxyproline, dermal remodelling and potent antioxidant activity

  20. Preferential blockade of dioxin-induced activation of the aryl hydrocarbon receptor by Antrodia camphorata.

    PubMed

    Mukai, Mai; Hayakawa, Kunihiro; Okamura, Maro; Tagawa, Yasuhiro; Nakajima, Shotaro; Saito, Yukinori; Takahashi, Shuhei; Yao, Jian; Nishimura, Daisuke; Sugi, Masahito; Matsunaga, Masaji; Kitamura, Masanori

    2009-09-01

    Halogenated and polycyclic aromatic hydrocarbons are widely distributed pollutants in environments. These toxic substances activate the aryl hydrocarbon receptor (AhR) and thereby cause a broad spectrum of pathological changes. Development of AhR inhibitors will be useful for prevention of diseases caused by AhR activation. Using the dioxin responsive element (DRE)-based sensing via secreted alkaline phosphatase (DRESSA), we examined effects of Antrodia camphorata, a mycerial extract, on the activation of AhR by halogenated and polycyclic aromatic hydrocarbons. We found that Antrodia camphorata markedly suppressed activation of AhR triggered by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In contrast, activation of AhR by polycyclic aromatic hydrocarbons (benzo[a]pyrene and 3-methylcholanthrene) was inhibited only modestly by this mycelium. Similarly, Antrodia camphorata only mildly attenuated activation of AhR by cigarette smoke that contains polycyclic aromatic hydrocarbons. Consistent with these results, Northern blot analysis revealed that DRE-driven exogenous and endogenous gene expression triggered by TCDD was abolished by Antrodia camphorata, whereas it did not substantially affect DRE-induced transcription triggered by benzo[a]pyrene, 3-methylcholanthrene or cigarette smoke. We also found that the inhibitory effect of Antrodia camphorata on TCDD-induced AhR activation was ascribed to neither down-regulation of AhR, down-regulation of the AhR nuclear translocator, nor up-regulation of the AhR repressor. These results suggest that Antrodia camphorata preferentially inhibits AhR activation and DRE-dependent gene expression triggered by dioxin.

  1. Allergic responses and aryl hydrocarbon receptor novel pathway of mast cell activation.

    PubMed

    Sibilano, Riccardo; Pucillo, Carlo E; Gri, Giorgia

    2015-01-01

    The activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact.

  2. High activity redox catalysts synthesized by chemical vapor impregnation.

    PubMed

    Forde, Michael M; Kesavan, Lokesh; Bin Saiman, Mohd Izham; He, Qian; Dimitratos, Nikolaos; Lopez-Sanchez, Jose Antonio; Jenkins, Robert L; Taylor, Stuart H; Kiely, Christopher J; Hutchings, Graham J

    2014-01-28

    The use of precious metals in heterogeneous catalysis relies on the preparation of small nanoparticles that are stable under reaction conditions. To date, most conventional routes used to prepare noble metal nanoparticles have drawbacks related to surface contamination, particle agglomeration, and reproducibility restraints. We have prepared titania-supported palladium (Pd) and platinum (Pt) catalysts using a simplified vapor deposition technique termed chemical vapor impregnation (CVI) that can be performed in any standard chemical laboratory. These materials, composed of nanoparticles typically below 3 nm in size, show remarkable activity under mild conditions for oxidation and hydrogenation reactions of industrial importance. We demonstrate the preparation of bimetallic Pd-Pt homogeneous alloy nanoparticles by this new CVI method, which show synergistic effects in toluene oxidation. The versatility of our CVI methodology to be able to tailor the composition and morphology of supported nanoparticles in an easily accessible and scalable manner is further demonstrated by the synthesis of Pdshell-Aucore nanoparticles using CVI deposition of Pd onto preformed Au nanoparticles supported on titania (prepared by sol immobilization) in addition to the presence of monometallic Au and Pd nanoparticles.

  3. TCDD dysregulation of 13 AHR-target genes in rat liver

    SciTech Connect

    Watson, John D.; Prokopec, Stephenie D.; Smith, Ashley B.; Okey, Allan B.; Pohjanvirta, Raimo; Boutros, Paul C.

    2014-02-01

    Despite several decades of research, the complete mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been shown that the AHR is required for all major manifestations of toxicity, the specific downstream changes involved in the development of toxic phenotypes remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in many species and tissues. We profiled their hepatic mRNA abundances in two rat strains with very different sensitivities to TCDD: the TCDD-sensitive Long–Evans (Turku/AB; L–E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated doses ranging from 0 to 3000 μg/kg at 19 h after TCDD exposure and time points ranging from 1.5 to 384 h after exposure to 100 μg/kg TCDD. Twelve of 13 genes responded to TCDD in at least one strain, and seven of these showed statistically significant inter-strain differences in the time course analysis (Aldh3a1, Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr, Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as association with additional transcriptional modulators. Of the 12 genes that responded to TCDD during the dose–response analysis, none had an ED{sub 50} equivalent to that of Cyp1a1, the most sensitive gene in this study, while nine genes responded to doses at least 10–100 fold higher, in at least one strain (Ahrr (L–E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L–E), Inmt (both), Nfe2l2 (L–E), Nqo1 (L–E) and Tiparp (both)). These data shed new light on the association of the AHR target genes with TCDD toxicity, and in particular the seven genes exhibiting strain-specific differences represent strong candidate mediators of Type-II toxicities. - Highlights: • NanoString measured hepatic mRNA molecules

  4. Generator of chemically active low-temperature plasma

    NASA Astrophysics Data System (ADS)

    Tyuftyaev, A. S.; Gadzhiev, M. Kh; Sargsyan, M. A.; Demirov, N. A.; Spector, N. O.

    2016-11-01

    A new generator of high enthalpy (H 0 > 40 kJ/g), chemically active nitrogen and air plasmas was designed and constructed. Main feature of the generator is an expanding channel of an output electrode; the generator belongs to the class of DC plasma torches with thermionic cathode with an efficiency of 80%. The generator ensures the formation of a slightly divergent plasma jet (2α = 12°) with a diameter of D = 10-12 mm, an electric arc maximum power of 20-50 kW, plasma forming gas flow rate 1.0-2.0 g/s, and the average plasma temperature at an outlet of 8000-11000 K.

  5. Thymus vulgaris essential oil: chemical composition and antimicrobial activity.

    PubMed

    Borugă, O; Jianu, C; Mişcă, C; Goleţ, I; Gruia, A T; Horhat, F G

    2014-01-01

    The study was designed to determine the chemical composition and antimicrobial properties of the essential oil of Thymus vulgaris cultivated in Romania. The essential oil was isolated in a yield of 1.25% by steam distillation from the aerial part of the plant and subsequently analyzed by GC-MS. The major components were p-cymene (8.41%), γ-terpinene (30.90%) and thymol (47.59%). Its antimicrobial activity was evaluated on 7 common food-related bacteria and fungus by using the disk diffusion method. The results demonstrate that the Thymus vulgaris essential oil tested possesses strong antimicrobial properties, and may in the future represent a new source of natural antiseptics with applications in the pharmaceutical and food industry.

  6. Enhancement of immunotoxin activity using chemical and biological reagents.

    PubMed Central

    Wu, M.

    1997-01-01

    One of the major discoveries of effective therapeutics is the use of targeted treatment, such as antibody-directed toxins, i.e. immunotoxins; however, this medicine delivery strategy is still at a developmental stage. A number of problems need to be resolved; one is their inefficacy when applied in vivo. Research has stimulated interest in this area through the use of chemical reagents and other moieties to increase the activity of immunotoxins. In this article, reagents that can potentiate the cytotoxicity of immunotoxins are reviewed and the mechanisms that increase activity of immunotoxins are discussed. Lysosomotropic amines, especially ammonium chloride and chloroquine, may raise the pH value of the lysosome in which the conjugates enter. Carboxylic ionophores, e.g. monensin, can influence Golgi vacuolation, which may facilitate the routing of conjugates, augmenting activity. Calcium channel antagonists may increase immunotoxin killing through morphological or other mechanisms that are not yet well understood. Viral particles and surface structure can enhance the cytotoxicity of conjugates, probably through the mechanism of disrupting endosomes. In addition, cytokines, beta-adrenergic blockers, immunosuppressive agents (cyclosporin A) and some antibiotics (daunorubicin) can be used to increase the effect of immunotoxins. PMID:9155057

  7. Antibacterial activity of silver bionanocomposites synthesized by chemical reduction route

    PubMed Central

    2012-01-01

    Background The aim of this study is to investigate the functions of polymers and size of nanoparticles on the antibacterial activity of silver bionanocomposites (Ag BNCs). In this research, silver nanoparticles (Ag NPs) were incorporated into biodegradable polymers that are chitosan, gelatin and both polymers via chemical reduction method in solvent in order to produce Ag BNCs. Silver nitrate and sodium borohydride were employed as a metal precursor and reducing agent respectively. On the other hand, chitosan and gelatin were added as a polymeric matrix and stabilizer. The antibacterial activity of different sizes of silver nanoparticles was investigated against Gram-positive and Gram-negative bacteria by the disk diffusion method using Mueller-Hinton Agar. Results The properties of Ag BNCs were studied as a function of the polymer weight ratio in relation to the use of chitosan and gelatin. The morphology of the Ag BNCs films and the distribution of the Ag NPs were also characterized. The diameters of the Ag NPs were measured and their size is less than 20 nm. The antibacterial trait of silver/chitosan/gelatin bionanocomposites was investigated. The silver ions released from the Ag BNCs and their antibacterial activities were scrutinized. The antibacterial activities of the Ag BNC films were examined against Gram-negative bacteria (E. coli and P. aeruginosa) and Gram-positive (S. aureus and M. luteus) by diffusion method using Muller-Hinton agar. Conclusions The antibacterial activity of Ag NPs with size less than 20 nm was demonstrated and showed positive results against Gram-negative and Gram-positive bacteria. The Ag NPs stabilized well in the polymers matrix. PMID:22967920

  8. Active sampling technique to enhance chemical signature of buried explosives

    NASA Astrophysics Data System (ADS)

    Lovell, John S.; French, Patrick D.

    2004-09-01

    Deminers and dismounted countermine engineers commonly use metal detectors, ground penetrating radar and probes to locate mines. Many modern landmines have a very low metal content, which severely limits the effectiveness of metal detectors. Canines have also been used for landmine detection for decades. Experiments have shown that canines smell the explosives which are known to leak from most types of landmines. The fact that dogs can detect landmines indicates that vapor sensing is a viable approach to landmine detection. Several groups are currently developing systems to detect landmines by "sniffing" for the ultra-trace explosive vapors above the soil. The amount of material that is available to passive vapor sensing systems is limited to no more than the vapor in equilibrium with the explosive related chemicals (ERCs) distributed in the surface soils over and near the landmine. The low equilibrium vapor pressure of TNT in the soil/atmosphere boundary layer and the limited volume of the boundary layer air imply that passive chemical vapor sensing systems require sensitivities in the picogram range, or lower. ADA is working to overcome many of the limitations of passive sampling methods, by the use of an active sampling method that employs a high-powered (1,200+ joules) strobe lamp to create a highly amplified plume of vapor and/or ERC-bearing fine particulates. Initial investigations have demonstrated that this approach can amplify the detectability of TNT by two or three orders of magnitude. This new active sampling technique could be used with any suitable explosive sensor.

  9. Dynamic model for selective metabolic activation in chemical carcinogenesis

    SciTech Connect

    Selkirk, J.K.; MacLeod, M.C.

    1980-01-01

    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  10. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  11. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    SciTech Connect

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  12. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice.

    PubMed

    Long, Xiaoru; Xie, Jun; Zhao, Keting; Li, Wei; Tang, Wei; Chen, Sisi; Zang, Na; Ren, Luo; Deng, Yu; Xie, Xiaohong; Wang, Lijia; Fu, Zhou; Liu, Enmei

    2016-10-01

    RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection.

  13. Chemical activation by mechanochemical mixing, microwave, and ultrasonic irradiation

    EPA Science Inventory

    The use of emerging MW-assisted chemistry techniques in conjunction with benign reaction media is dramatically reducing chemical waste ad reaction times in several organic syntheses and chemical transformations. This editorial comments on the recent developments in mechanochemica...

  14. THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To de...

  15. Chemical Variability and Biological Activities of Eucalyptus spp. Essential Oils.

    PubMed

    Barbosa, Luiz Claudio Almeida; Filomeno, Claudinei Andrade; Teixeira, Robson Ricardo

    2016-12-07

    Many plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in Nature and have been utilized by mankind for different purposes, such as pharmaceuticals, agrochemicals, aromatherapy, and food flavorants. There are more than 3000 EOs reported in the literature, with approximately 300 in commercial use, including the EOs from Eucalyptus species. Most EOs from Eucalyptus species are rich in monoterpenes and many have found applications in pharmaceuticals, agrochemicals, food flavorants, and perfumes. Such applications are related to their diverse biological and organoleptic properties. In this study, we review the latest information concerning the chemical composition and biological activities of EOs from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus, we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricidal, insecticidal and herbicidal activities, hoping that such information will contribute to the development of research in this field. It is also intended that the information described in this study can be useful in the rationalization of the use of Eucalyptus EOs as components for pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

  16. Chemically modified RNA activated matrices enhance bone regeneration.

    PubMed

    Elangovan, Satheesh; Khorsand, Behnoush; Do, Anh-Vu; Hong, Liu; Dewerth, Alexander; Kormann, Michael; Ross, Ryan D; Sumner, D Rick; Allamargot, Chantal; Salem, Aliasger K

    2015-11-28

    There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation.

  17. Removal of toxic chemicals from water with activated carbon

    USGS Publications Warehouse

    Dawson, V.K.; Marking, L.L.; Bills, T.D.

    1976-01-01

    Activated carbon was effective in removing fish toxicants and anesthetics from water solutions. Its capacity to adsorb 3-trifluoromethyl-4-nitrophenol (TFM), antimycin, NoxfishA? (5% rotenone), Dibrorms, juglone, MSa??222, and benzocaine ranged from 0.1 to 64 mg per gram of carbon. The adsorptive capacity (end point considered as a significant discharge) of activated carbon for removal of TFM was determined at column depths of 15, 30, and 60 cm; temperatures of 7, 12, 17, and 22 C; pH's of 6.5, 7.5, 8.5, and 9.5; and flow rates of 50, 78, 100, 200, and 940 ml/min. Adsorptive capacity increased when the contact time was increased by reducing the flow rate or increasing the column depth. The adsorptive capacity was not significantly influenced by temperature but was substantially higher at pH 6.5 than at the other pH's tested. A practical and efficient filter for purifying chemically treated water was developed.

  18. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  19. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  20. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  1. Do Training Programs Work? An Assessment of Pharmacists Activities in the Field of Chemical Dependency.

    ERIC Educational Resources Information Center

    Brooks, Valerie G.; Brock, Tina Penick; Ahn, Jungeun

    2001-01-01

    Seeks to determine if pharmacists who attended a chemical dependency training program were performing more chemical dependency related activities. Results reveal that participants were more likely to perform the following activities: lecture to community groups about chemical dependency; participate in a pharmacists' recovery program; provide…

  2. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  3. Chemical Composition and Antioxidant Activities of Broussonetia papyrifera Fruits

    PubMed Central

    Sun, Jie; Liu, Shao-fang; Zhang, Chu-shu; Yu, Li-na; Bi, Jie; Zhu, Feng; Yang, Qing-li

    2012-01-01

    Fruits of Broussonetia papyrifera from South China were analyzed for their total chemical composition, and antioxidant activities in ethanol and aqueous extracts. In the fruit of this plant, the crude protein, crude fat and carbohydrates was 7.08%, 3.72% and 64.73% of dry weight, respectively. The crude protein, crude fat and carbohydrates were 15.71%, 20.51% and 36.09% of dry weight, respectively. Fatty acid and amino acid composition of the fruit were analyzed. Unsaturated fatty acid concentration was 70.6% of the total fatty acids. The percentage of the essential amino acids (EAAs) was 40.60% of the total amino acids. Furthermore, B. papyrifera fruit are rich in many mineral elements and vitamins. Total phenolic content was assessed using the Folin-Ciocalteau assay, whereas antioxidant activities were assessed by measuring the ability of the two extracts to scavenge DPPH radicals, inhibit peroxidation, and chelate ferric ions. Their reducing power was also assessed. Results indicated that the aqueous extract of B. papyrifera was a more potent reducing agent and radical-scavenger than the ethanol extract. GC–MS analysis of the ethanol extract showed the presence of some acid-containing compounds. The changes in total phenolic content and antioxidant capacity in B. papyrifera from four different regions grown under normal conditions were assessed. The antioxidant activity of different extracts was positively associated with their total phenolic content. These results suggest that the fruit of B. papyrifera could be used in dietary supplement preparations, or as a food additive, for nutritional gain, or to prevent oxidation in food products. PMID:22389678

  4. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  5. Chemically activated carbon from lignocellulosic wastes for heavy metal wastewater remediation: Effect of activation conditions.

    PubMed

    Nayak, Arunima; Bhushan, Brij; Gupta, Vartika; Sharma, P

    2017-05-01

    Chemical activation is known to induce specific surface features of porosity and functionality which play a definite role in enhancing the adsorptive potential of the developed activated carbons. Different conditions of temperature, time, reagent type and impregnation ratio were applied on sawdust precursor and their effect on the physical, surface chemical features and finally on the adsorption potential of the developed activated carbons were analysed. Under activation conditions of 600°C, 1hr, 1:0.5 ratio, ZnCl2 impregnated carbon (CASD_ZnCl2) resulted in microporosity while KOH impregnation (CASD_KOH) yielded a carbon having a wider pore size distribution. The surface chemistry revealed similar functionalities. At same pH, temperature and adsorbate concentrations, CASD_KOH demonstrated better adsorption potential (1.06mmoles/g for Cd(2+) and 1.61mmoles/g for Ni(2+)) in comparison to CASD_ZnCl2 (0.23mmoles/g and 0.33mmoles/g for Cd(2+) and Ni(2+) respectively). Other features were a short equilibrium time of 60mins and an adsorbent dose of 0.2g/L for the CASD_KOH in comparison to CASD_ZnCl2 (equilibrium time of 150min and dosage of 0.5g/L). The nature of interactions was physical for both adsorbents and pore diffusion mechanisms were operative. The results reveal the potentiality of chemical activation so as to achieve the best physico-chemical properties suited for energy efficient, economical and eco-friendly water treatment.

  6. Disruption of CLOCK-BMAL1 Transcriptional Activity Is Responsible for Aryl Hydrocarbon Receptor–Mediated Regulation of Period1 Gene

    PubMed Central

    Xu, Can-Xin; Krager, Stacey L.; Liao, Duan-Fang; Tischkau, Shelley A.

    2010-01-01

    The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)–dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and β-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants. PMID:20106950

  7. Discussion of the Separation of Chemical and Relaxational Kinetics of Chemically Activated Intermediates in Master Equation Simulations.

    PubMed

    Döntgen, Malte; Leonhard, Kai

    2017-03-02

    Chemical activation of intermediates, such as hydrogen abstraction products, is emerging as a basis for a fully new reaction type: hot β-scission. While for thermally equilibrated intermediates chemical kinetics are typically orders of magnitude slower than relaxational kinetics, chemically activated intermediates raise the issue of inseparable chemical and relaxational kinetics. Here, this separation problem is discussed in the framework of master equation simulations, proposing three cases often encountered in chemistry: insignificant chemical activation, predominant chemical activation, and the transition between these two limits. These three cases are illustrated via three example systems: methoxy (CH3Ȯ), diazenyl (ṄNH), and methyl formate radicals (CH3OĊO). For diazenyl, it is found that hot β-scission fully replaces the sequence of hydrogen abstraction and β-scission of thermally equilibrated diazenyl. Building on the example systems, a rule of thumb is proposed that can be used to intuitively judge the significance of hot β-scission: if the reverse hydrogen abstraction barrier height is comparable to or larger than the β-scission barrier height, hot β-scission should be considered in more detail.

  8. Two-phase flow in a chemically active porous medium

    SciTech Connect

    Darmon, Alexandre Dauchot, Olivier; Benzaquen, Michael; Salez, Thomas

    2014-12-28

    We study the problem of the transformation of a given reactant species into an immiscible product species, as they flow through a chemically active porous medium. We derive the equation governing the evolution of the volume fraction of the species, in a one-dimensional macroscopic description, identify the relevant dimensionless numbers, and provide simple models for capillary pressure and relative permeabilities, which are quantities of crucial importance when tackling multiphase flows in porous media. We set the domain of validity of our models and discuss the importance of viscous coupling terms in the extended Darcy’s law. We investigate numerically the steady regime and demonstrate that the spatial transformation rate of the species along the reactor is non-monotonous, as testified by the existence of an inflection point in the volume fraction profiles. We obtain the scaling of the location of this inflection point with the dimensionless lengths of the problem. Eventually, we provide key elements for optimization of the reactor.

  9. Thymus mastichina: chemical constituents and their anti-cancer activity.

    PubMed

    Gordo, Joana; Máximo, Patrícia; Cabrita, Eurico; Lourenço, Ana; Oliva, Abel; Almeida, Joana; Filipe, Mariana; Cruz, Pedro; Barcia, Rita; Santos, Miguel; Cruz, Helder

    2012-11-01

    The cytotoxicity-guided study of the dichloromethane and ethanol extracts of Thymus mastichina L. using the HCT colon cancer cell line allowed the identification of nine compounds, sakuranetin (1), sterubin (2), oleanolic acid (3), ursolic acid (4), lutein (5), beta-sitosterol (6), rosmarinic acid (7), 6-hydroxyluteolin-7-O-beta-glucopyranoside (8), and 6-hydroxyapigenin-7-O-beta-glucopyranoside (9). All compounds were tested for their cytotoxicity against the HCT colon cancer cell line. Compound 4 showed cytotoxicity with GI50 value of 6.8 microg/mL. A fraction composed of a mixture (1:1) of triterpenoid acids 3 and 4 displayed improved cytotoxicity with a GI50 of 2.8 microg/mL suggesting a synergistic behavior. This is the first report on the chemical constituents of Thymus mastichina L. based on structural assignments by spectroscopic analysis. The presence of these constituents identified by colon cancer cytotoxicity-guided activity indicates that extracts of T. mastichina L. may have a protective effect against colon cancers.

  10. Adsorption of copper cyanide on chemically active adsorbents

    SciTech Connect

    Lee, J.S.; Deorkar, N.V.; Tavlarides, L.L.

    1998-07-01

    An inorganic chemically active adsorbent (ICAA), SG(1)-TEPA (tetraethylenepentaamine)-propyl, is developed for removal, recovery, and recycling of copper cyanide from industrial waste streams. Equilibrium studies are executed to determine and model adsorption of the copper cyanide complex from aqueous solutions in a batch and packed column. It appears that adsorption is dependent on anionic copper cyanide species and the basicity of the ligand. Aqueous-phase equilibrium modeling shows that monovalent (Cu(CN){sub 2}{sup {minus}}), divalent (Cu(CN){sub 3}{sup 2{minus}}), and trivalent (Cu(CN){sub 4}{sup 3{minus}}) species of copper cyanide exist in the solution, depending on the pH and the concentration of total cyanide ions. Batch adsorption data are modeled using a modified multicomponent Langmuir isotherm which includes aqueous-phase speciation and basicity of the SG(1)-TEPA-propyl. This developed model is applied with a mass balance equation to describe the adsorption of copper cyanide complexes in a packed column.

  11. Chemical and thermal modulation of molecular motor activities

    NASA Astrophysics Data System (ADS)

    Hong, Weili

    Molecular motors of kinesin and dynein families are responsible for various intracellular activities, from long distance movement of organelles, vesicles, protein complexes, and mRNAs to powering mitotic processes. They can take nanometer steps using chemical energy from the hydrolysis of ATP (adenosine triphosphate), and their dysfunction is involved in many neurodegenerative diseases that require long distance transport of cargos. Here I report on the study of the properties of molecular motors at a single-molecule level using optical trappings. I first studied the inhibition properties of kinesin motors by marine natural compound adociasulfates. I showed that adociasulfates compete with microtubules for binding to kinesins and thus inhibit kinesins' activity. Although adociasulfates are a strong inhibitor for all kinesin members, they show a much higher inhibition effect for conventional kinesins than for mitotic kinesins. Thus adociasulfates can be used to specifically inhibit conventional kinesins. By comparing the inhibition of kinesins by two structurally similar adociasulfates, one can see that the negatively charged sulfate residue of adociasulfates can be replaced by other negative residues and thus make it possible for adociasulfate-derived compounds to be more cell permeable. Kinesins and dyneins move cargos towards opposite directions along a microtubule. Cargos with both kinesins and dyneins attached often move bidirectionally due to undergoing a tug-of-war between the oppositely moving kinesin and dynein motors. Here I studied the effect of temperature on microtubule-based kinesin and dynein motor transport. While kinesins' and dyneins' velocities are closely matched above 15 °C, below this temperature the dyneins' velocity decreases much faster than the kinesins'. The kinesins' and dyneins' forces do not measurably change with temperature. The results suggest that temperature has significant effects on bidirectional transport and can be used to

  12. Effects of the environmental contaminants DEHP and TCDD on estradiol synthesis and aryl hydrocarbon receptor and peroxisome proliferator-activated receptor signalling in the human granulosa cell line KGN.

    PubMed

    Ernst, Jana; Jann, Johann-Christoph; Biemann, Ronald; Koch, Holger M; Fischer, Bernd

    2014-09-01

    Environmental contaminants binding to transcription factors, such as the aryl hydrocarbon receptor (AhR) and the alpha and gamma peroxisome proliferator-activated receptors (PPARs), contribute to adverse effects on the reproductive system. Expressing both the AhR and PPARs, the human granulosa cell line KGN offers the opportunity to investigate the regulatory mechanisms involved in receptor crosstalk, independent of overriding hormonal control. The aim of the present study was to investigate the impact of two environmental contaminants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an AhR ligand) and di-(2-ethylhexyl) phthalate (DEHP, a PPAR ligand), on gonadotrophin sensitivity and estrogen synthesis in KGN cells. Accumulation of the DEHP metabolite mono-(2-ethylhexyl) phthalate (MEHP) in DEHP-exposed cells was measured by high-performance liquid chromatography mass spectrometry, thereby demonstrating DEHP metabolism to MEHP by KGN cells. By employing TCDD ( an AhR agonist), rosiglitazone (a PPARgamma agonist) or bezafibrate (a PPARalpha agonist), the presence of a functional AhR and PPAR cascade was confirmed in KGN cells. Cytotoxicity testing revealed no effect on KGN cell proliferation for the concentrations of TCDD and DEHP used in the current study. FSH-stimulated cells were exposed to TCDD, DEHP or a mix of both and estradiol synthesis was measured by enzyme-linked immunosorbent assay and gene expression by quantitative RT-PCR. Exposure decreased estradiol synthesis (TCDD, DEHP, mix) and reduced the mRNA expression of CYP19 aromatase (DEHP, mix) and FSHR (DEHP). DEHP induced the expression of the alpha and gamma PPARs and AhR, an effect which was inhibited by selective PPAR antagonists. Studies in the human granulosa cell line KGN show that the action of endocrine-disrupting chemicals may be due to a direct activation of AhR, for example by TCDD, and by a transactivation via PPARs, for example by DEHP, inducing subsequent transcriptional changes with a broad

  13. Heat-activated Plasmonic Chemical Sensors for Harsh Environments

    SciTech Connect

    Carpenter, Michael; Oh, Sang-Hyun

    2015-12-01

    A passive plasmonics based chemical sensing system to be used in harsh operating environments was investigated and developed within this program. The initial proposed technology was based on combining technologies developed at the SUNY Polytechnic Institute Colleges of Nanoscale Science and Engineering (CNSE) and at the University of Minnesota (UM). Specifically, a passive wireless technique developed at UM was to utilize a heat-activated plasmonic design to passively harvest the thermal energy from within a combustion emission stream and convert this into a narrowly focused light source. This plasmonic device was based on a bullseye design patterned into a gold film using focused ion beam methods (FIB). Critical to the design was the use of thermal stabilizing under and overlayers surrounding the gold film. These stabilizing layers were based on both atomic layer deposited films as well as metal laminate layers developed by United Technologies Aerospace Systems (UTAS). While the bullseye design was never able to be thermally stabilized for operating temperatures of 500oC or higher, an alternative energy harvesting design was developed by CNSE within this program. With this new development, plasmonic sensing results are presented where thermal energy is harvested using lithographically patterned Au nanorods, replacing the need for an external incident light source. Gas sensing results using the harvested thermal energy are in good agreement with sensing experiments, which used an external incident light source. Principal Component Analysis (PCA) was used to reduce the wavelength parameter space from 665 variables down to 4 variables with similar levels of demonstrated selectivity. The method was further improved by patterning rods which harvested energy in the near infrared, which led to a factor of 10 decrease in data acquisition times as well as demonstrated selectivity with a reduced wavelength data set. The combination of a plasmonic-based energy harvesting

  14. The Influence of Chemical Chaperones on Enzymatic Activity under Thermal and Chemical Stresses: Common Features and Variation among Diverse Chemical Families

    PubMed Central

    Feibish, Nir; Sharon, Noa; Schnaider, Lee; Shmul, Guy; Amir, Yaniv; Buzhansky, Ludmila; Gazit, Ehud

    2014-01-01

    Molecular and chemical chaperones are key components of the two main mechanisms that ensure structural stability and activity under environmental stresses. Yet, chemical chaperones are often regarded only as osmolytes and their role beyond osmotic regulation is not fully understood. Here, we systematically studied a large group of chemical chaperones, representatives of diverse chemical families, for their protective influence under either thermal or chemical stresses. Consistent with previous studies, we observed that in spite of the structural similarity between sugars and sugar alcohols, they have an apparent difference in their protective potential. Our results support the notion that the protective activity is mediated by the solvent and the presence of water is essential. In the current work we revealed that i) polyols and sugars have a completely different profile of protective activity toward trifluoroethanol and thermal stress; ii) minor changes in solvent composition that do not affect enzyme activity, yet have a great effect on the ability of osmolytes to act as protectants and iii) increasing the number of active groups of carbohydrates makes them better protectants while increasing the number of active groups of methylamines does not, as revealed by attempts to synthesize de novo designed methylamines with multiple functional groups. PMID:24520396

  15. The influence of chemical chaperones on enzymatic activity under thermal and chemical stresses: common features and variation among diverse chemical families.

    PubMed

    Levy-Sakin, Michal; Berger, Or; Feibish, Nir; Sharon, Noa; Schnaider, Lee; Shmul, Guy; Amir, Yaniv; Buzhansky, Ludmila; Gazit, Ehud

    2014-01-01

    Molecular and chemical chaperones are key components of the two main mechanisms that ensure structural stability and activity under environmental stresses. Yet, chemical chaperones are often regarded only as osmolytes and their role beyond osmotic regulation is not fully understood. Here, we systematically studied a large group of chemical chaperones, representatives of diverse chemical families, for their protective influence under either thermal or chemical stresses. Consistent with previous studies, we observed that in spite of the structural similarity between sugars and sugar alcohols, they have an apparent difference in their protective potential. Our results support the notion that the protective activity is mediated by the solvent and the presence of water is essential. In the current work we revealed that i) polyols and sugars have a completely different profile of protective activity toward trifluoroethanol and thermal stress; ii) minor changes in solvent composition that do not affect enzyme activity, yet have a great effect on the ability of osmolytes to act as protectants and iii) increasing the number of active groups of carbohydrates makes them better protectants while increasing the number of active groups of methylamines does not, as revealed by attempts to synthesize de novo designed methylamines with multiple functional groups.

  16. Phthalides: Distribution in Nature, Chemical Reactivity, Synthesis, and Biological Activity.

    PubMed

    León, Alejandra; Del-Ángel, Mayela; Ávila, José Luis; Delgado, Guillermo

    2017-01-01

    oxidation, reduction, addition, elimination, and cycloaddition reactions, and treatments with Lewis acids of (Z)-ligustilide have afforded linear dimers. Some intramolecular condensations and differentiated cyclizations of the dimeric phthalides have been carried out, providing evidences for the particular chemical reactivity of these compounds.Several structural modifications of phthalides have been carried out subjecting them to microbial transformations by different species of bacteria, fungi and algae, and these included resolutions of racemic mixtures and oxidations, among others.The [π4s + π2s] and [π2s + π2s] cycloadditions of (Z)-ligustilide for the synthesis of dimeric phthalides have been reported, and different approaches involving cyclizations, Alder-Rickert reactions, Sharpless asymmetric hydroxylations, or Grignard additions have been used for the synthesis of monomeric phthalides. The use of phthalides as building blocks for divergent oriented synthesis has been proven.Many of the naturally occurring phthalides display different biological activities including antibacterial, antifungal, insecticidal, cytotoxic, and anti-inflammatory effects, among many others, with a considerable recent research on the topic. In the case of compounds isolated from the Apiaceae, the bioactivities correlate with the traditional medicinal uses of the natural sources. Some monomeric phthalides have shown their ability to attenuate certain neurological diseases, including stroke, Alzheimer's and Parkinson's diseases.The present contribution covers the distribution of phthalides in nature and the findings in the structural diversity, chemical reactivity, biotransformations, syntheses, and bioactivity of natural and semisynthetic phthalides.

  17. Synergistic activation of estrogen receptor with combinations of environmental chemicals

    SciTech Connect

    Arnold, S.F.; Klotz, D.M.; Collins, B.M.

    1996-06-07

    Certain chemicals in the environment are estrogenic. The low potencies of the compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen potencies of combination of such chemicals were screened in a simple yeast estrogen systems (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 100 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses. 32 refs., 3 figs., 3 tabs.

  18. Transactivation activity of human, zebrafish, and rainbow trout aryl hydrocarbon receptors expressed in COS-7 cells: greater insight into species differences in toxic potency of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners.

    PubMed

    Abnet, C C; Tanguay, R L; Heideman, W; Peterson, R E

    1999-08-15

    Transactivation assays were used to compare the potency and efficacy of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners in activating aryl hydrocarbon receptors (AhRs) from rainbow trout (rtAhR2alpha and rtAhR2beta), zebrafish (zfAhR2), and human (huAhR), respectively. All AhRs were expressed with their species-specific AhR nuclear translocator (ARNT) in COS-7 cells. Transactivation activity was determined for two PCDD, two PCDF, and seven PCB congeners with each of the four AhR/ARNT pairs using prt1Aluc, a luciferase reporter driven by two dioxin-responsive enhancer elements (DREs) from the rainbow trout cyp1A gene. Maximal-fold induction, EC50, and relative potency values were calculated for congeners that exhibited dose-related activity in the assay. Of the four AhR/ARNT pairs tested with PCDD, PCDF, and non-ortho PCB congeners, three exhibited high activity (rainbow trout AhR2alpha, zebrafish AhR2, and human AhR), while rainbow trout AhR2beta had very weak or no activity. Comparisons between these AhRs showed that while mono-ortho PCBs were able to activate the human AhR, they were generally ineffective in activating rainbow trout and zebrafish AhR2s. This supports the hypothesis that structural differences between mammalian and fish AhRs may account for differences in relative potencies of the mono-ortho PCBs between mammals and fish. Another important finding was a significant difference in transactivation activity between the two rainbow trout AhR2 isoforms despite the fact that they are 95% identical at the amino acid level. For all PCDD, PCDF, and PCB agonists tested, rainbow trout AhR2alpha was significantly more active than AhR2beta. However, rainbow trout AhR2beta is active as a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-activated transcription factor, with enhancer elements from the mouse cyp1A gene. This suggests that AhR2beta may have evolved to serve a different physiological function than AhR2alpha in

  19. Advanced deposition model for thermal activated chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Cai, Dang

    Thermal Activated Chemical Vapor Deposition (TACVD) is defined as the formation of a stable solid product on a heated substrate surface from chemical reactions and/or dissociation of gaseous reactants in an activated environment. It has become an essential process for producing solid film, bulk material, coating, fibers, powders and monolithic components. Global market of CVD products has reached multi billions dollars for each year. In the recent years CVD process has been extensively used to manufacture semiconductors and other electronic components such as polysilicon, AlN and GaN. Extensive research effort has been directed to improve deposition quality and throughput. To obtain fast and high quality deposition, operational conditions such as temperature, pressure, fluid velocity and species concentration and geometry conditions such as source-substrate distance need to be well controlled in a CVD system. This thesis will focus on design of CVD processes through understanding the transport and reaction phenomena in the growth reactor. Since the in situ monitor is almost impossible for CVD reactor, many industrial resources have been expended to determine the optimum design by semi-empirical methods and trial-and-error procedures. This approach has allowed the achievement of improvements in the deposition sequence, but begins to show its limitations, as this method cannot always fulfill the more and more stringent specifications of the industry. To resolve this problem, numerical simulation is widely used in studying the growth techniques. The difficulty of numerical simulation of TACVD crystal growth process lies in the simulation of gas phase and surface reactions, especially the latter one, due to the fact that very limited kinetic information is available in the open literature. In this thesis, an advanced deposition model was developed to study the multi-component fluid flow, homogeneous gas phase reactions inside the reactor chamber, heterogeneous surface

  20. PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model

    PubMed Central

    Larsen, Michele Campaigne; N'jai, Alhaji; Czuprynski, Charles J.

    2016-01-01

    7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM) leading to mature cell losses as replenishment fails. These losses are mediated by Cyp1b1, independent of the AhR, despite induction of Cyp1b1. BM mesenchymal progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is minimally induced. PreB colony forming unit activity (PreB CFU) is lost within 24 hours in isolated BM cells (BMC) unless cocultured with cells derived from primary MPC (BMS2 line). The mouse embryonic OP9 line, which provides more efficient coculture support, shares similar induction-resistant Cyp1b1 characteristics. This OP9 support is suppressed by DMBA, which is then prevented by Cyp1b1 inhibitors. OP9-enriched medium partially sustains CFU activities but loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1. PreB CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA. BMC gene expression profiles identified cytokines and developmental factors that are substantially changed in Cyp1b1-ko mice. DMBA had few effects in WT mice but systematically modified many clustered responses in Cyp1b1-ko mice. Typical BMC AhR-responsive genes were insensitive to Cyp1b1 deletion. TCDD replicated Cyp1b1 interventions, suggesting alternative AhR mediation. Cyp1b1 also diminishes oxidative stress, a key cause of stem cell instability. PMID:27891153

  1. Combined Chemical Activation and Fenton Degradation to Convert Waste Polyethylene into High-Value Fine Chemicals.

    PubMed

    Chow, Cheuk-Fai; Wong, Wing-Leung; Ho, Keith Yat-Fung; Chan, Chung-Sum; Gong, Cheng-Bin

    2016-07-04

    Plastic waste is a valuable organic resource. However, proper technologies to recover usable materials from plastic are still very rare. Although the conversion/cracking/degradation of certain plastics into chemicals has drawn much attention, effective and selective cracking of the major waste plastic polyethylene is extremely difficult, with degradation of C-C/C-H bonds identified as the bottleneck. Pyrolysis, for example, is a nonselective degradation method used to crack plastics, but it requires a very high energy input. To solve the current plastic pollution crisis, more effective technologies are needed for converting plastic waste into useful substances that can be fed into the energy cycle or used to produce fine chemicals for industry. In this study, we demonstrate a new and effective chemical approach by using the Fenton reaction to convert polyethylene plastic waste into carboxylic acids under ambient conditions. Understanding the fundamentals of this new chemical process provides a possible protocol to solve global plastic-waste problems.

  2. Activation of aryl hydrocarbon receptor promotes invasion of clear cell renal cell carcinoma and is associated with poor prognosis and cigarette smoke.

    PubMed

    Ishida, Masaru; Mikami, Shuji; Shinojima, Toshiaki; Kosaka, Takeo; Mizuno, Ryuichi; Kikuchi, Eiji; Miyajima, Akira; Okada, Yasunori; Oya, Mototsugu

    2015-07-15

    Although exposure to environmental pollutants is one of the risk factors for renal cell carcinoma (RCC), its relationship with carcinogenesis and the progression of RCC remains unknown. The present study was designed to elucidate the role of the aryl hydrocarbon receptor (AhR), a major mediator of carcinogenesis caused by environmental pollutants, in the progression of RCC. The expression of AhR was investigated in 120 patients with RCC using immunohistochemistry, and its relationship with clinicopathological parameters and prognoses was statistically analyzed. RCC cell lines were exposed to indirubin or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), AhR ligands, to activate the AhR pathway, or were transfected with small interfering RNA (siRNA) for AhR. The expression of the AhR target genes CYP1A1 and CYP1B1, matrix metalloproteinases (MMPs), and invasion through Matrigel(TM) were then examined. AhR was predominantly expressed in the nuclei of high-grade clear cell RCC (ccRCC) and tumor-infiltrating lymphocytes (TILs), and its expression levels in cancer cells and TILs correlated with the pathological tumor stage and histological grade. A multivariate Cox analysis revealed that the strong expression of AhR in cancer cells was a significant and independent predictor of disease-specific survival. AhR ligands up-regulated the expression of AhR and CYPs and promoted invasion by up-regulating MMPs. Furthermore, siRNA for AhR down-regulated CYPs, and inhibited cancer cell invasion together with the down-regulation of MMPs. These results suggest that AhR regulates the invasion of ccRCC and may be involved in tumor immunity. Therefore, inhibiting the activation of AhR may represent a potentially attractive therapeutic target for ccRCC patients.

  3. Active targeting in a random porous medium by chemical swarm robots with secondary chemical signaling

    NASA Astrophysics Data System (ADS)

    Grančič, Peter; Štěpánek, František

    2011-08-01

    The multibody dynamics of a system of chemical swarm robots in a porous environment is investigated. The chemical swarm robots are modeled as Brownian particles capable of delivering an encapsulated chemical payload toward a given target location and releasing it in response to an external stimulus. The presence of chemical signals (chemo-attractant) in the system plays a crucial role in coordinating the collective movement of the particles via chemotaxis. For a number of applications, such as distributed chemical processing and targeted drug delivery, the understanding of factors that govern the collective behavior of the particles, especially their ability to localize a given target, is of immense importance. A hybrid modeling methodology based on the combination of the Brownian dynamics method and diffusion problem coupled through the chemotaxis phenomena is used to analyze the impact of a varying signaling threshold and the strength of chemotaxis on the ability of the chemical robots to fulfill their target localization mission. The results demonstrate that the selected performance criteria (the localization half time and the success rate) can be improved when an appropriate signaling process is chosen. Furthermore, for an optimum target localization strategy, the topological complexity of the porous environment needs to be reflected.

  4. Improved calibration of IMU biases in analytic coarse alignment for AHRS

    NASA Astrophysics Data System (ADS)

    Lu, Jiazhen; Lei, Chaohua; Li, Baoguo; Wen, Ting

    2016-07-01

    An improved method for the inertial measurement unit (IMU) calibration of coarse alignment for the low-accuracy attitude heading reference system (AHRS) is proposed in this paper. The sensitivities of the Euler angles with respect to the inertial sensor biases are studied based on the analytic coarse alignment principle, and the errors of earth rotation rate and local gravity in the body frame caused by initial attitude error are analyzed. Then, an improved analytic coarse alignment algorithm with accelerometer and gyro bias calibration in an arbitrary three-position is proposed. Simulation and experiment results show that the novel method can calibrate accelerometer and gyro biases, reduce Euler angle attitude error, and improve navigation precision in practical applications. Moreover, this method can be applied to other low-accuracy inertial navigation systems.

  5. The design and performance of a 200 A-hr lithium-metal sulfide cell

    NASA Astrophysics Data System (ADS)

    Askew, B. A.; Dand, P. V.

    The near-term performance goals of 90-100 W-hr/kg specific energy (C/4 rate) and 90-100 W/kg peak specific power are achieved in five-plate 200 A-hr cells using a boron nitride felt separator and wire screen or photoetched electrode constraint systems. Specific energy values greater than 100 W-hr/kg are attained at lower rates (C/6) in cells of similar design using a magnesia powder separator. A marked dependence of temperature on cell capacity is found in cells using lithium chloride-potassium chloride electrolyte over the temperature range 445-470 C. It is thought that an alternative electrolyte composition may be necessary to reduce this effect in the battery.

  6. Access Path to the Ligand Binding Pocket May Play a Role in Xenobiotics Selection by AhR

    PubMed Central

    Szöllősi, Dániel; Erdei, Áron; Gyimesi, Gergely; Magyar, Csaba; Hegedűs, Tamás

    2016-01-01

    Understanding of multidrug binding at the atomic level would facilitate drug design and strategies to modulate drug metabolism, including drug transport, oxidation, and conjugation. Therefore we explored the mechanism of promiscuous binding of small molecules by studying the ligand binding domain, the PAS-B domain of the aryl hydrocarbon receptor (AhR). Because of the low sequence identities of PAS domains to be used for homology modeling, structural features of the widely employed HIF-2α and a more recent suitable template, CLOCK were compared. These structures were used to build AhR PAS-B homology models. We performed molecular dynamics simulations to characterize dynamic properties of the PAS-B domain and the generated conformational ensembles were employed in in silico docking. In order to understand structural and ligand binding features we compared the stability and dynamics of the promiscuous AhR PAS-B to other PAS domains exhibiting specific interactions or no ligand binding function. Our exhaustive in silico binding studies, in which we dock a wide spectrum of ligand molecules to the conformational ensembles, suggest that ligand specificity and selection may be determined not only by the PAS-B domain itself, but also by other parts of AhR and its protein interacting partners. We propose that ligand binding pocket and access channels leading to the pocket play equally important roles in discrimination of endogenous molecules and xenobiotics. PMID:26727491

  7. Musashi-2 Attenuates AHR Signaling to Expand Human Hematopoietic Stem Cells

    PubMed Central

    Rentas, Stefan; Voisin, Veronique; Wilhelm, Brian T; Bader, Gary D; Yeo, Gene W; Hope, Kristin J

    2016-01-01

    Umbilical cord blood (CB)-derived hematopoietic stem cells (HSCs) are essential in many life saving regenerative therapies, but their low number in CB units has significantly restricted their clinical use despite the advantages they provide during transplantation1. Select small molecules that enhance hematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified2,3, however, in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular pathways that underpin the unique human HSC self-renewal program will facilitate the development of targeted strategies that expand these critical cell types for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs4,5, the post-transcriptional mechanisms guiding HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein (RBP) Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we determined that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signaling through post-transcriptional downregulation of canonical AHR pathway components in CB HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and give evidence that manipulating such networks ex vivo can provide a novel means to enhance the regenerative potential of human HSCs. PMID:27121842

  8. Aryl hydrocarbon receptor activation inhibits in vitro differentiation of human monocytes and Langerhans dendritic cells.

    PubMed

    Platzer, Barbara; Richter, Susanne; Kneidinger, Doris; Waltenberger, Darina; Woisetschläger, Maximilian; Strobl, Herbert

    2009-07-01

    The transcription factor aryl hydrocarbon receptor (AhR) represents a promising therapeutic target in allergy and autoimmunity. AhR signaling induced by the newly described ligand VAF347 inhibits allergic lung inflammation as well as suppresses pancreatic islet allograft rejection. These effects are likely mediated via alterations in dendritic cell (DC) function. Moreover, VAF347 induces tolerogenic DCs. Langerhans cells (LCs) are immediate targets of exogenous AhR ligands at epithelial surfaces; how they respond to AhR ligands remained undefined. We studied AhR expression and function in human LCs and myelopoietic cell subsets using a lineage differentiation and gene transduction model of human CD34(+) hematopoietic progenitors. We found that AhR is highly regulated during myeloid subset differentiation. LCs expressed highest AhR levels followed by monocytes. Conversely, neutrophil granulocytes lacked AhR expression. AhR ligands including VAF347 arrested the differentiation of monocytes and LCs at an early precursor cell stage, whereas progenitor cell expansion or granulopoiesis remained unimpaired. AhR expression was coregulated with the transcription factor PU.1 during myeloid subset differentiation. VAF347 inhibited PU.1 induction during initial monocytic differentiation, and ectopic PU.1 restored monocyte and LC generation in the presence of this compound. AhR ligands failed to interfere with cytokine receptor signaling during LC differentiation and failed to impair LC activation/maturation. VAF347-mediated antiproliferative effect on precursors undergoing LC lineage differentiation occurred in a clinically applicable serum-free culture model and was not accompanied by apoptosis induction. In conclusion, AhR agonist signaling interferes with transcriptional processes leading to monocyte/DC lineage commitment of human myeloid progenitor cells.

  9. Endocrine disrupting chemicals targeting estrogen receptor signaling: Identification and mechanisms of action

    PubMed Central

    Shanle, Erin K.; Xu, Wei

    2011-01-01

    Many endocrine disrupting chemicals (EDCs) adversely impact estrogen signaling by interacting with two estrogen receptors (ERs): ERα and ERβ. Though the receptors have similar ligand binding and DNA binding domains, ERα and ERβ have some unique properties in terms of ligand selectivity and target gene regulation. EDCs that target ER signaling can modify genomic and non-genomic ER activity through direct interactions with ERs, indirectly through transcription factors like the aryl hydrocarbon receptor (AhR), or through modulation of metabolic enzymes that are critical for normal estrogen synthesis and metabolism. Many EDCs act through multiple mechanisms as exemplified by chemicals that bind both AhR and ER, such as 3-methylcholanthrene. Other EDCs that target ER signaling include phytoestrogens, bisphenolics, and organochlorine pesticides and many alter normal ER signaling through multiple mechanisms. EDCs can also display tissue-selective ER agonist and antagonist activities similar to selective estrogen receptor modulators (SERMs) designed for pharmaceutical use. Thus, biological effects of EDCs need to be carefully interpreted because EDCs can act through complex tissue-selective modulation of ERs and other signaling pathways in vivo. Current requirements by the U.S. Environmental Protection Agency require some in vitro and cell-based assays to identify EDCs that target ER signaling through direct and metabolic mechanisms. Additional assays may be useful screens for identifying EDCs that act through alternative mechanisms prior to further in vivo study. PMID:21053929

  10. Chemical properties and toxicity of soils contaminated by mining activity.

    PubMed

    Agnieszka, Baran; Tomasz, Czech; Jerzy, Wieczorek

    2014-09-01

    This research is aimed at assessing the total content and soluble forms of metals (zinc, lead and cadmium) and toxicity of soils subjected to strong human pressure associated with mining of zinc and lead ores. The research area lay in the neighbourhood of the Bolesław Mine and Metallurgical Plant in Bukowno (Poland). The study obtained total cadmium concentration between 0.29 and 51.91 mg, zinc between 7.90 and 3,614 mg, and that of lead between 28.4 and 6844 mg kg(-1) of soil d.m. The solubility of the heavy metals in 1 mol dm(-3) NH4NO3 was 1-49% for zinc, 5-45% for cadmium, and <1-10% for lead. In 1 mol HCl dm(-3), the solubility of the studied metals was much higher and obtained values depending on the collection site, from 45 to 92% for zinc, from 74 to 99%, and from 79 to 99% for lead. The lower solubility of the heavy metals in 1 mol dm(-3) NH4NO3 than 1 mol HCl dm(-3) is connected with that, the ammonium nitrate has low extraction power, and it is used in determining the bioavailable (active) form of heavy metals. Toxicity assessment of the soil samples was performed using two tests, Phytotoxkit and Microtox(®). Germination index values were between 22 and 75% for Sinapis alba, between 28 and 100% for Lepidium sativum, and between 10 and 28% for Sorghum saccharatum. Depending on the studied soil sample, Vibrio fischeri luminescence inhibition was 20-96%. The sensitivity of the test organisms formed the following series: S. saccharatum > S. alba = V. fischeri > L. sativum. Significant positive correlations (p ≤ 0.05) of the total and soluble contents of the metals with luminescence inhibition in V. fischeri and root growth inhibition in S. saccharatum were found. The general trend observed was an increase in metal toxicity measured by the biotest with increasing available metal contents in soils. All the soil samples were classified into toxicity class III, which means that they are toxic and present severe danger. Biotest are a good complement to

  11. AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels

    SciTech Connect

    Barrett, R.J.; Appell, K.C.; Kilpatrick, B.F.; Proakis, A.G.; Nolan, J.C.; Walsh, D.A. )

    1991-01-01

    In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) (3H)ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) (3H)nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing.

  12. Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment.

    PubMed

    Fujisawa, Yasuko; Li, Wen; Wu, Dalei; Wong, Patrick; Vogel, Christoph; Dong, Bin; Kung, Hsing-Jien; Matsumura, Fumio

    2011-10-01

    It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in certain types of breast tumors. However, so far no concrete evidence has been provided yet as to why and how the overexpressed AHR in those cancer cells is functionally activated without exogenous ligands. Here we show that the AHR was functionally activated when estrogen receptor-negative, AHR overexpressing MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation. Artificial over-expression of ETK in P20E cells through transfection with wild-type ETK plasmid (ETK-wt) caused up-regulation of cytochrome P4501a1 (CYP1A1; a marker of functional activation of AHR). Furthermore, ablation of ETK expression by a specific antisense oligonucleotide or AG879, a specific inhibitor of ETK kinase suppressed activation of AHR induced by omeprazole, a strong ligand-independent activator of AHR. Activation of ETK in those cells conferred them resistance to UVB- as well as doxorubicin-induced apoptosis, both of which were reversed by ETK-KQ. Together, these findings support our conclusion that ETK is the tyrosine kinase responsible for the functional activation of the AHR in these mammary epithelial cells.

  13. The screening of chemicals for juvenoid-related endocrine activity using the water flea Daphnia magna.

    PubMed

    Wang, Helen Ying; Olmstead, Allen W; Li, Hong; Leblanc, Gerald A

    2005-09-10

    U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.

  14. LIMITED-USE CHEMICAL PROTECTIVE CLOTHING FOR EPA SUPERFUND ACTIVITIES

    EPA Science Inventory

    Because contractor field personnel complained about the poor durability and fit of limited-use chemical protective clothing (CPC) most commonly used at hazardous waste site operations, the U.S. Environmental Protection Agency (EPA) initiated a study to • characterize use of CPC...

  15. Adsorption studies of methylene blue and phenol onto vetiver roots activated carbon prepared by chemical activation.

    PubMed

    Altenor, Sandro; Carene, Betty; Emmanuel, Evens; Lambert, Jacques; Ehrhardt, Jean-Jacques; Gaspard, Sarra

    2009-06-15

    Vetiver roots have been utilized for the preparation of activated carbon (AC) by chemical activation with different impregnation ratios of phosphoric acid, X(P) (gH(3)PO(4)/g precursor): 0.5:1; 1:1 and 1.5:1. Textural characterization, determined by nitrogen adsorption at 77K shows that mixed microporous and mesoporous structures activated carbons (ACs) with high surface area (>1000 m(2)/g) and high pore volume (up to 1.19 cm(3)/g) can be obtained. The surface chemical properties of these ACs were investigated by X-ray photoelectron spectroscopy (XPS) and Boehm titration. Their textural and chemical characteristics were compared to those of an AC sample obtained by steam activation of vetiver roots. Classical molecules used for characterizing liquid phase adsorption, phenol and methylene blue (MB), were used. Adsorption kinetics of MB and phenol have been studied using commonly used kinetic models, i.e., the pseudo-first-order model, the pseudo-second-order model, the intraparticle diffusion model and as well the fractal, BWS (Brouers, Weron and Sotolongo) kinetic equation. The correlation coefficients (R(2)) and the normalized standard deviation Deltaq (%) were determined showing globally, that the recently derived fractal kinetic equation could best describe the adsorption kinetics for the adsorbates tested here, indicating a complex adsorption mechanism. The experimental adsorption isotherms of these molecules on the activated carbon were as well analysed using four isotherms: the classical Freundlich, Langmuir, Redlich-Peterson equations, but as well the newly published deformed Weibull Brouers-Sotolongo isotherm. The results obtained from the application of the equations show that the best fits were achieved with the Brouers-Sotolongo equation and with the Redlich-Peterson equation. Influence of surface functional groups towards MB adsorption is as well studied using various ACs prepared from vetiver roots and sugar cane bagasse. Opposite effects governing MB

  16. The combined effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and the phytoestrogen genistein on steroid hormone secretion, AhR and ERβ expression and the incidence of apoptosis in granulosa cells of medium porcine follicles

    PubMed Central

    PIASECKA-SRADER, Joanna; SADOWSKA, Agnieszka; NYNCA, Anna; ORLOWSKA, Karina; JABLONSKA, Monika; JABLONSKA, Olga; PETROFF, Brian K.; CIERESZKO, Renata E.

    2015-01-01

    Low doses of endocrine disrupting chemicals (EDCs) used in combination may act in a manner different from that of individual compounds. The objective of the study was to examine in vitro effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 100 pM) and genistein (500 nM) on: 1) progesterone (P4) and estradiol (E2) secretion (48 h); 2) dynamic changes in aryl hydrocarbon receptor (AhR) mRNA and protein expression (1, 3, 6, 24 and 48 h); 3) dynamic changes in estrogen receptor β (ERβ) mRNA and protein expression (1, 3, 6, 24 and 48 h); and 4) induction of apoptosis in porcine granulosa cells derived from medium follicles (3, 6 and 24 h). TCDD had no effect on P4 or E2 production, but potentiated the inhibitory effect of genistein on P4 production. In contrast to the individual treatments which did not produce any effects, TCDD and genistein administered together decreased ERβ and AhR protein expression in granulosa cells. Moreover, the inhibitory effect of TCDD on AhR mRNA expression was abolished by genistein. The treatments did not induce apoptosis in the cells. In summary, combined effects of low concentrations of TCDD and genistein on follicular function of pigs differed from that of individual compounds. The results presented in the current paper clearly indicate that effects exerted by low doses of EDCs applied in combination must be taken into consideration when studying potential risk effects of EDCs on biological processes. PMID:26568065

  17. Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis

    SciTech Connect

    Reynolds, S.H.; Stowers, S.J.; Patterson, R.M.; Maronpot, R.R.; Anderson, M.W.

    1988-06-01

    The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

  18. Chemical modification of capuramycins to enhance antibacterial activity

    PubMed Central

    Bogatcheva, Elena; Dubuisson, Tia; Protopopova, Marina; Einck, Leo; Nacy, Carol A.; Reddy, Venkata M.

    2011-01-01

    Objectives To extend capuramycin spectrum of activity beyond mycobacteria and improve intracellular drug activity. Methods Three capuramycin analogues (SQ997, SQ922 and SQ641) were conjugated with different natural and unnatural amino acids or decanoic acid (DEC) through an ester bond at one or more available hydroxyl groups. In vitro activity of the modified compounds was determined against Mycobacterium spp. and representative Gram-positive and Gram-negative bacteria. Intracellular activity was evaluated in J774A.1 mouse macrophages infected with Mycobacterium tuberculosis (H37Rv). Results Acylation of SQ997 and SQ641 with amino undecanoic acid (AUA) improved in vitro activity against most of the bacteria tested. Conjugation of SQ922 with DEC, but not AUA, improved its activity against Gram-positive bacteria. In the presence of efflux pump inhibitor phenylalanine arginine β-naphthyl amide, MICs of SQ997-AUA, SQ641-AUA and SQ922-DEC compounds improved even further against drug-susceptible and drug-resistant Staphylococcus aureus. In Gram-negative bacteria, EDTA-mediated permeabilization caused 4- to 16-fold enhancement of the activity of AUA-conjugated SQ997, SQ922 and SQ641. Conjugation of all three capuramycin analogues with AUA improved intracellular killing of H37Rv in murine macrophages. Conclusions Conjugation of capuramycin analogues with AUA or DEC enhanced in vitro activity, extended the spectrum of activity in Gram-positive bacteria and increased intracellular activity against H37Rv. PMID:21186194

  19. Activation of the aryl hydrocarbon receptor induces hepatic steatosis via the upregulation of fatty acid transport.

    PubMed

    Kawano, Yuki; Nishiumi, Shin; Tanaka, Shinwa; Nobutani, Kentaro; Miki, Akira; Yano, Yoshihiko; Seo, Yasushi; Kutsumi, Hiromu; Ashida, Hitoshi; Azuma, Takeshi; Yoshida, Masaru

    2010-12-15

    The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix/Per-ARNT-Sim domain transcription factor, which is activated by various xenobiotic ligands. AHR is known to be abundant in liver tissue and to be associated with hepatic steatosis. However, it has not yet been elucidated how the activation of AHR promotes hepatic steatosis. The aim of this study is to clarify the role of AHR in hepatic steatosis. The intraperitoneal injection of 3-methylcholanthrene (3MC), a potent AHR ligand, into C57BL/6J mice significantly increased the levels of triglycerides and six long-chain monounsaturated fatty acids in the livers of mice, resulting in hepatic microvesicular steatosis. 3MC significantly enhanced the expression level of fatty acid translocase (FAT), a factor regulating the uptake of long-chain fatty acids into hepatocytes, in the liver. In an in vitro experiment using human hepatoma HepG2 cells, 3MC increased the expression level of FAT, and the downregulation of AHR by AHR siRNA led to the suppression of 3MC-induced FAT expression. In addition, the mRNA level of peroxisome proliferator-activated receptor (PPAR) α, an upstream factor of FAT, was increased in the livers of 3MC-treated mice. Taking together, AHR activation induces hepatic microvesicular steatosis by increasing the expression level of FAT.

  20. Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

    SciTech Connect

    Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T.

    2012-11-15

    Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.

  1. Chemical transformations on botryane skeleton. Effect on the cytotoxic activity.

    PubMed

    Reino, José L; Durán-Patrón, Rosa; Segura, Inmaculada; Hernández-Galán, Rosario; Riese, Hans H; Collado, Isidro G

    2003-03-01

    Eighteen compounds with a botryane skeleton have been obtained through chemical transformations of various toxins from the fungus Botrytis cinerea. During the course of these transformations, the C-10 carbon of the botryane skeleton was found to exhibit an interesting high regioselectivity to oxidizing and reducing agents. In addition, the cytotoxicity of 27 botryane derivatives was determined in vitro against Hs578T, MDA-MB-231, HT-1080, U87-MG, IMR-90, and HUVEC cell lines. The results of this study confirm that the cytotoxicity of botrydial (1) and its derivatives is related to the presence of a 1,5-dialdehyde functionality.

  2. Functional Imaging of Chemically Active Surfaces with Optical Reporter Microbeads

    PubMed Central

    Ahuja, Punkaj; Nair, Sumitha; Narayan, Sreenath; Gratzl, Miklós

    2015-01-01

    We have developed a novel approach to allow for continuous imaging of concentration fields that evolve at surfaces due to release, uptake, and mass transport of molecules, without significant interference of the concentration fields by the chemical imaging itself. The technique utilizes optical “reporter” microbeads immobilized in a thin layer of transparent and inert hydrogel on top of the surface. The hydrogel has minimal density and therefore diffusion in and across it is like in water. Imaging the immobilized microbeads over time provides quantitative concentration measurements at each location where an optical reporter resides. Using image analysis in post-processing these spatially discrete measurements can be transformed into contiguous maps of the dynamic concentration field across the entire surface. If the microbeads are small enough relative to the dimensions of the region of interest and sparsely applied then chemical imaging will not noticeably affect the evolution of concentration fields. In this work colorimetric optode microbeads a few micrometers in diameter were used to image surface concentration distributions on the millimeter scale. PMID:26332766

  3. Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.

    PubMed

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Beitel, Shawn C; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2015-04-07

    Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.

  4. Active Metamaterial Based Terahertz Polarimeter for Spectroscopic Detection of Chemical and Biological Hazards

    DTIC Science & Technology

    2014-04-01

    Active Metamaterial Based Terahertz Polarimeter for Spectroscopic Detection of Chemical and Biological Hazards by Grace D. Metcalfe ...for Spectroscopic Detection of Chemical and Biological Hazards Grace D. Metcalfe and Michael Wraback Sensors and Electron Devices Directorate, ARL...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Grace D. Metcalfe , Michael Wraback, Richard D. Averitt, and Xin Zhang 5d. PROJECT NUMBER

  5. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Restrictions on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL...

  6. HIGH-DIMENSIONAL PROFILING OF TRANSCRIPTION FACTOR ACTIVITY DIFFERENTIATES TOXCAST CHEMICAL GROUPS

    EPA Science Inventory

    The ToxCast™ project at the U.S. EPA uses a diverse battery of high throughput screening assays and informatics models to rapidly characterize the activity of chemicals. A central goal of the project is to provide empirical evidence to aid in the prioritization of chemicals for a...

  7. Phenylthiourea as a weak activator of aryl hydrocarbon receptor inhibiting 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 transcription in zebrafish embryo.

    PubMed

    Wang, Wen-Der; Wang, Yin; Wen, Hui-Ju; Buhler, Donald R; Hu, Chin-Hwa

    2004-07-01

    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that can be activated by a diverse synthetic and naturally-occurring chemicals, such as the halogenated aromatic hydrocarbons (HAHs) and the non-halogenated polycyclic aromatic hydrocarbons (PAHs). The liganded AHR modulates the genetic activity of a variety of xenobiotic-responsive genes, including cytochrome P4501A1 (CYP1A1). The tyrosinase inhibitor 1-phenyl-2-thiourea (PTU) is widely used in zebrafish research to suppress pigmentation in developing embryos/fry. Here we showed that 0.2 mM PTU induced a basal level of CYP1A1 transcription in zebrafish embryonic integument as early as 24 h postfertilization (hpf) stage. Subsequently, PTU induced CYP1A1 transcription in blood vessels at 36 hpf. During larval stage, the liver and all pharyngeal arch vessels of PTU-treated embryos exhibited CYP1A1 transcription as well. Comparing to TCDD, PTU induces CYP1A1 transcription with much lower efficacy in zebrafish embryos. Coincubating the embryos with PTU and TCDD led to repressing TCDD-induced CYP1A1 transcription. Mechanistic studies indicated that both of PTU- and TCDD-mediated CYP1A1 transcriptions are modulated by the same AHR-ARNT signaling pathway.

  8. Hydrogeology, chemical and microbial activity measurement through deep permafrost

    SciTech Connect

    Stotler, R.L.; Frape, S.K.; Freifeld, B.M.; Holden, B.; Onstott, T.C.; Ruskeeniemi, T.; Chan, E.

    2010-04-01

    Little is known about hydrogeochemical conditions beneath thick permafrost, particularly in fractured crystalline rock, due to difficulty in accessing this environment. The purpose of this investigation was to develop methods to obtain physical, chemical, and microbial information about the subpermafrost environment from a surface-drilled borehole. Using a U-tube, gas and water samples were collected, along with temperature, pressure, and hydraulic conductivity measurements, 420 m below ground surface, within a 535 m long, angled borehole at High Lake, Nunavut, Canada, in an area with 460-m-thick permafrost. Piezometric head was well above the base of the permafrost, near land surface. Initial water samples were contaminated with drill fluid, with later samples <40% drill fluid. The salinity of the non-drill fluid component was <20,000 mg/L, had a Ca/Na ratio above 1, with {delta}{sup 18}O values {approx}5{per_thousand} lower than the local surface water. The fluid isotopic composition was affected by the permafrost-formation process. Nonbacteriogenic CH{sub 4} was present and the sample location was within methane hydrate stability field. Sampling lines froze before uncontaminated samples from the subpermafrost environment could be obtained, yet the available time to obtain water samples was extended compared to previous studies. Temperature measurements collected from a distributed temperature sensor indicated that this issue can be overcome easily in the future. The lack of methanogenic CH{sub 4} is consistent with the high sulfate concentrations observed in cores. The combined surface-drilled borehole/U-tube approach can provide a large amount of physical, chemical, and microbial data from the subpermafrost environment with few, controllable, sources of contamination.

  9. Hydrogeology, chemical and microbial activity measurement through deep permafrost.

    PubMed

    Stotler, Randy L; Frape, Shaun K; Freifeld, Barry M; Holden, Brian; Onstott, Tullis C; Ruskeeniemi, Timo; Chan, Eric

    2011-01-01

    Little is known about hydrogeochemical conditions beneath thick permafrost, particularly in fractured crystalline rock, due to difficulty in accessing this environment. The purpose of this investigation was to develop methods to obtain physical, chemical, and microbial information about the subpermafrost environment from a surface-drilled borehole. Using a U-tube, gas and water samples were collected, along with temperature, pressure, and hydraulic conductivity measurements, 420 m below ground surface, within a 535 m long, angled borehole at High Lake, Nunavut, Canada, in an area with 460-m-thick permafrost. Piezometric head was well above the base of the permafrost, near land surface. Initial water samples were contaminated with drill fluid, with later samples <40% drill fluid. The salinity of the non-drill fluid component was <20,000 mg/L, had a Ca/Na ratio above 1, with δ(18) O values ∼5‰ lower than the local surface water. The fluid isotopic composition was affected by the permafrost-formation process. Nonbacteriogenic CH(4) was present and the sample location was within methane hydrate stability field. Sampling lines froze before uncontaminated samples from the subpermafrost environment could be obtained, yet the available time to obtain water samples was extended compared to previous studies. Temperature measurements collected from a distributed temperature sensor indicated that this issue can be overcome easily in the future. The lack of methanogenic CH(4) is consistent with the high sulfate concentrations observed in cores. The combined surface-drilled borehole/U-tube approach can provide a large amount of physical, chemical, and microbial data from the subpermafrost environment with few, controllable, sources of contamination.

  10. Hydrogeology, Chemical and Microbial Activity Measurement Through Deep Permafrost

    USGS Publications Warehouse

    Stotler, R.L.; Frape, S.K.; Freifeld, B.M.; Holden, B.; Onstott, T.C.; Ruskeeniemi, T.; Chan, E.

    2011-01-01

    Little is known about hydrogeochemical conditions beneath thick permafrost, particularly in fractured crystalline rock, due to difficulty in accessing this environment. The purpose of this investigation was to develop methods to obtain physical, chemical, and microbial information about the subpermafrost environment from a surface-drilled borehole. Using a U-tube, gas and water samples were collected, along with temperature, pressure, and hydraulic conductivity measurements, 420 m below ground surface, within a 535 m long, angled borehole at High Lake, Nunavut, Canada, in an area with 460-m-thick permafrost. Piezometric head was well above the base of the permafrost, near land surface. Initial water samples were contaminated with drill fluid, with later samples <40% drill fluid. The salinity of the non-drill fluid component was <20,000 mg/L, had a Ca/Na ratio above 1, with ??18O values ???5??? lower than the local surface water. The fluid isotopic composition was affected by the permafrost-formation process. Nonbacteriogenic CH4 was present and the sample location was within methane hydrate stability field. Sampling lines froze before uncontaminated samples from the subpermafrost environment could be obtained, yet the available time to obtain water samples was extended compared to previous studies. Temperature measurements collected from a distributed temperature sensor indicated that this issue can be overcome easily in the future. The lack of methanogenic CH4 is consistent with the high sulfate concentrations observed in cores. The combined surface-drilled borehole/U-tube approach can provide a large amount of physical, chemical, and microbial data from the subpermafrost environment with few, controllable, sources of contamination. ?? 2010 The Author(s). Journal compilation ?? 2010 National Ground Water Association.

  11. Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals.

    PubMed

    Thomas, Paul; Dawick, James; Lampi, Mark; Lemaire, Philippe; Presow, Shaun; van Egmond, Roger; Arnot, Jon A; Mackay, Donald; Mayer, Philipp; Galay Burgos, Malyka

    2015-10-20

    Toxicological research in the 1930s gave the first indications of the link between narcotic toxicity and the chemical activity of organic chemicals. More recently, chemical activity has been proposed as a novel exposure parameter that describes the fraction of saturation and that quantifies the potential for partitioning and diffusive uptake. In the present study, more than 2000 acute and chronic algal, aquatic invertebrates and fish toxicity data, as well as water solubility and melting point values, were collected from a series of sources. The data were critically reviewed and grouped by mode of action (MoA). We considered 660 toxicity data to be of acceptable quality. The 328 data which applied to the 72 substances identified as MoA 1 were then evaluated within the activity-toxicity framework: EC50 and LC50 values for all three taxa correlated generally well with (subcooled) liquid solubilities. Acute toxicity was typically exerted within the chemical activity range of 0.01-0.1, whereas chronic toxicity was exerted in the range of 0.001-0.01. These results confirm that chemical activity has the potential to contribute to the determination, interpretation and prediction of toxicity to aquatic organisms. It also has the potential to enhance regulation of organic chemicals by linking results from laboratory tests, monitoring and modeling programs. The framework can provide an additional line of evidence for assessing aquatic toxicity, for improving the design of toxicity tests, reducing animal usage and addressing chemical mixtures.

  12. Quantum Chemical Studies on Stability and Chemical Activities in Calcium Ion Bound Calmodulin Loops.

    PubMed

    Sikdar, Samapan; Ghosh, Mahua; De Raychaudhury, Molly; Chakrabarti, J

    2015-11-19

    Quantum chemical (QC) calculations for macromolecules require truncation of the molecule, highlighting the portion of interest due to heavy computation cost. As a result, an estimation of the effects of truncation is important to interpret the energy spectrum of such calculations. We perform density functional theory based QC calculations on calcium ion bound EF-hand loops of Calmodulin isolated from the crystal structure in an implicit solvent. We find that the terminal contributions of neutral capping are negligible across the entire ground-state energy spectrum. The coordination energy range and the nature of hybridization of the coordination state molecular orbitals remain qualitatively similar across these loops. While the HOMO and LUMO of loops in the N-terminal domain are dominated by the acidic aspartates, and the polar/hydrophobic residues, respectively, these levels of the C-terminal domain loops show strong localized electron density on the phenyl rings of the tyrosines. The Fukui index calculation identifies the hydroxyl oxygen in the phenyl ring of Y99 as a potent nucleophile. Our analysis indicates a general way of interpreting the electronic energy spectra to understand stability and functions of large biomolecules where the truncation of the molecule and, hence, the terminal capping effects are inevitable.

  13. Chemical Constituents Antioxidant and Anticholinesterasic Activity of Tabernaemontana catharinensis

    PubMed Central

    Moura, Sidnei; Echeverrigaray, Sergio

    2013-01-01

    The present work aimed to analyze the alkaloid content of the ethanolic extract of Tabernaemontana catharinensis (Apocynaceae family) and its fractions as well as to evaluate their antioxidant and anticholinesterasic activities. The analyses of the ethanolic extract of T. catharinensis by mass spectrometry allowed identifying the presence of the alkaloids 16-epi-affinine, coronaridine-hydroxyindolenine, voachalotine, voacristine-hydroxyindolenine, and 12-methoxy-n-methyl-voachalotine, as well as an alkaloid with m/z 385.21 whose spectrum suggests a derivative of voacristine or voacangine. The extract and its alkaloid rich fractions showed antioxidant activity, especially those that contain the alkaloid m/z 385.21 or 16-epi-affinine with DPPH scavenging activity (IC50) between 37.18 and 74.69 μg/mL. Moreover, the extract and its fractions exhibited anticholinesterasic activity, particularly the fractions characterized by the presence of 12-methoxy-n-methyl-voachalotine, with IC50 = 2.1 to 2.5 μg/mL. Fractions with 16-epi-affinine combined good antioxidant (IC50 = 65.59 to 74.69 μg/mL) and anticholinesterasic (IC50 = 7.7 to 8.3 μg/mL) activities, representing an option for further studies aimed at treating neurodegenerative diseases. PMID:23983637

  14. Foeniculum vulgare essential oils: chemical composition, antioxidant and antimicrobial activities.

    PubMed

    Miguel, Maria Graça; Cruz, Cláudia; Faleiro, Leonor; Simões, Mariana T F; Figueiredo, Ana Cristina; Barroso, José G; Pedro, Luis G

    2010-02-01

    The essential oils from Foeniculum vulgare commercial aerial parts and fruits were isolated by hydrodistillation, with different distillation times (30 min, 1 h, 2 h and 3 h), and analyzed by GC and GC-MS. The antioxidant ability was estimated using four distinct methods. Antibacterial activity was determined by the agar diffusion method. Remarkable differences, and worrying from the quality and safety point of view, were detected in the essential oils. trans-Anethole (31-36%), alpha-pinene (14-20%) and limonene (11-13%) were the main components of the essentials oil isolated from F. vulgare dried aerial parts, whereas methyl chavicol (= estragole) (79-88%) was dominant in the fruit oils. With the DPPH method the plant oils showed better antioxidant activity than the fruits oils. With the TBARS method and at higher concentrations, fennel essential oils showed a pro-oxidant activity. None of the oils showed a hydroxyl radical scavenging capacity > 50%, but they showed an ability to inhibit 5-lipoxygenase. The essential oils showed a very low antimicrobial activity. In general, the essential oils isolated during 2 h were as effective, from the biological activity point of view, as those isolated during 3 h.

  15. Push for new materials, chemicals from biomass sparks active R and D

    SciTech Connect

    Borman, S. )

    1990-09-01

    This paper discusses how a resurgence of interest in the production of new materials, chemicals, and fuels from biomass resources such as wood, cellulose, lignin, starch, and chitin is sparking active R and D efforts in these areas. Biobased materials and chemicals currently under development include composites of conventional plastics with lignocellulosics (chemicals from wood and other plant sources); lignocellulosic nonwoven mates that can be pressed into rigid shapes to form doors, walls, and even auto body parts; phenolic chemicals produced from wood waste and bark; membranes made from chitosan (a substance derived from crustacean shells); and biodegradable plastics containing starch.

  16. Chemical Bond Activation Observed with an X-ray Laser.

    PubMed

    Beye, Martin; Öberg, Henrik; Xin, Hongliang; Dakovski, Georgi L; Dell'Angela, Martina; Föhlisch, Alexander; Gladh, Jörgen; Hantschmann, Markus; Hieke, Florian; Kaya, Sarp; Kühn, Danilo; LaRue, Jerry; Mercurio, Giuseppe; Minitti, Michael P; Mitra, Ankush; Moeller, Stefan P; Ng, May Ling; Nilsson, Anders; Nordlund, Dennis; Nørskov, Jens; Öström, Henrik; Ogasawara, Hirohito; Persson, Mats; Schlotter, William F; Sellberg, Jonas A; Wolf, Martin; Abild-Pedersen, Frank; Pettersson, Lars G M; Wurth, Wilfried

    2016-09-15

    The concept of bonding and antibonding orbitals is fundamental in chemistry. The population of those orbitals and the energetic difference between the two reflect the strength of the bonding interaction. Weakening the bond is expected to reduce this energetic splitting, but the transient character of bond-activation has so far prohibited direct experimental access. Here we apply time-resolved soft X-ray spectroscopy at a free-electron laser to directly observe the decreased bonding-antibonding splitting following bond-activation using an ultrashort optical laser pulse.

  17. Cooperative enhancement of deoxyribozyme activity by chemical modification and added cationic copolymer

    PubMed Central

    Saito, Ken; Shimada, Naohiko; Maruyama, Atushi

    2016-01-01

    Abstract Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step and the turnover step should be improved for enhancing overall activity of DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by increasing turnover efficacy. In this paper, effects of the copolymer on DNAzymes modified with locked nucleic acids (LNA) or 2′-O-methylated (2′-OMe) nucleic acids were studied. The copolymer increased activity of these chemically modified DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity was observed with 2′-OMe-modified DNAzyme in the presence of the copolymer. DNAzyme catalytic activity was successfully enhanced by cooperation of the added copolymer and chemical modification of DNAzyme. PMID:27877894

  18. Chemical Modification of Papain and Subtilisin: An Active Site Comparison

    ERIC Educational Resources Information Center

    St-Vincent, Mireille; Dickman, Michael

    2004-01-01

    An experiment using methyle methanethiosulfonate (MMTS) and phenylmethylsulfonyl flouride (PMSF) to specifically modify the cysteine and serine residues in the active sites of papain and subtilism respectively is demonstrated. The covalent modification of these enzymes and subsequent rescue of papain shows the beginning biochemist that proteins…

  19. Incorporating Nondrug Social & Recreational Activities in Outpatient Chemical Dependency Treatment

    ERIC Educational Resources Information Center

    Siporin, Sheldon; Baron, Lisa

    2012-01-01

    "Contingency Management programs (CMP) and non-drug social and recreational activities (NDSRA) are interventions premised on behavior theory that rely on external sources of reinforcement alternative to drug-based forms to decrease drug use. CMP usually employs vouchers as reinforcement for negative toxicologies. Despite research support, CMP…

  20. Antifungal activities and chemical composition of some medicinal plants.

    PubMed

    Mohammadi, A; Nazari, H; Imani, S; Amrollahi, H

    2014-06-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists and natural-products scientists are combing the earth for phytochemicals and leads, which could be developed for treatment of infectious diseases. The aim of this study was to investigate the antifungal activities of the essential oils of some medicinal plants such as Stachys pubescens, Thymus kotschyanus, Thymus daenensis and Bupleurum falcatum against Fusarium oxysporum, Aspergillus flavus and Alternaria alternata. The essential oils were used to evaluate their MICs and MFCs compared to the amphotricin B as a standard drug. The essential oils were also analyzed by GC/MS. Essential oils isolated from the S. pubescens, T. kotschyanus and B. falcatum showed strong antifungal activities. The essential oil of T. daenensis exhibited a moderate activity against the selected fungi in comparison with the other plants' essential oils. In addition, the results showed that 26, 23, 22 and 15 components were identified from the essential oils of T. kotschyanus, S. pubescens, T. daenensis and B. falcatum, respectively. These oils exhibited a noticeable antifungal activity against the selected fungi. Regarding obtained results and that natural antimicrobial substances are inexpensive and have fewer side effects, they convey potential for implementation in fungal pathogenic systems.

  1. Essential oil from Artemisia phaeolepis: chemical composition and antimicrobial activities.

    PubMed

    Ben Hsouna, Anis; Ben Halima, Nihed; Abdelkafi, Slim; Hamdi, Naceur

    2013-01-01

    Artemisia phaeolepis, a perennial herb with a strong volatile odor, grows on the grasslands of Mediterranean region. Essential oil obtained from Artemisia phaeolepis was analyzed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. A total of 79 components representing 98.19% of the total oil were identified, and the main compounds in the oil were found to be eucalyptol (11.30%), camphor (8.21%), terpine-4-ol (7.32%), germacrene D (6.39), caryophyllene oxide (6.34%), and caryophyllene (5.37%). The essential oil showed definite inhibitory activity against 10 strains of test microorganisms. Eucalyptol, camphor, terpine-4-ol, caryophyllene, germacrene D and caryophyllene oxide were also examined as the major components of the oil. Camphor showed the strongest antimicrobial activity; terpine-4-ol, eucalyptol, caryophyllene and germacrene D were moderately active and caryophyllene oxide was weakly active. The study revealed that the antimicrobial properties of the essential oil can be attributed to the synergistic effects of its diverse major and minor components.

  2. Passive dosing of soil invertebrates with polycyclic aromatic hydrocarbons: limited chemical activity explains toxicity cutoff.

    PubMed

    Mayer, Philipp; Holmstrup, Martin

    2008-10-01

    The partitioning of organic soil pollutants into soil organisms is driven by their chemical activity, which normally does not exceed that of the pure pollutant. Passive dosing with the silicone poly(dimethylsiloxane) (PDMS) was used to initiate and maintain the maximum chemical activity of 10 polycyclic aromatic hydrocarbons (PAHs) in toxicity tests with the springtail Folsomia candida. The test animals could move freely on the PDMS saturated with PAHs, resulting in direct contact and exposure to saturated air. After 7 days, springtail lethality correlated neither with the octanol-water partition coefficients of the PAHs nor with their molecular size, but with their melting point All low-melting PAHs (T(M) < or = 110 degrees C) caused 100% lethality, whereas all high-melting PAHs (TM > or = 180 degrees C) caused no significant lethality. The lethality was successfully fitted to one chemical activity response curve for all PAHs tested, with effective chemical activity causing 50% lethality (Ea-50) of 0.058. It was also fitted to the PAH concentration in the PDMS, resulting in an EC(PDMS)-50 of 8.7 mM. Finally, the combined exposure to anthracene and pyrene was described by the sum of chemical activities causing lethality, in good agreement with the chemical activity-response curve obtained.

  3. Hypoglycemic activity evaluation and chemical study on hollyhock flowers.

    PubMed

    Zhang, Yi; Jin, Lijun; Chen, Qiu; Wu, Zhizhen; Dong, Yongzhe; Han, Lifeng; Wang, Tao

    2015-04-01

    Hollyhock (Althaea rosea (Linn.) Cavan) belongs to Althaea genus, Malvaceae family, is a perennial garden plant distributed throughout the world in warm temperate and tropical regions, which was used as anti-diabetes ingredient in traditional Chinese medicine. In the process of our research, ethanolic extract of hollyhock flower (HFE) was found to decrease serum triglyceride and glucose levels significantly in KK-A(y) mice after oral administration for 8weeks. Meanwhile, gene expressions on AMPK, IRS2, PI3K, AKT and GLUT4 in liver were remarkably up-regulated. Three new dihydroflavonol glycosides, named as roseaflavanonolosides A (1), B (2), and C (3), together with two known ones were obtained from HFE. Their structures were elucidated by chemical and spectroscopic methods. Hepatic cell glucose uptake experiment was performed using 2-NBDG as a glucose uptake indicator. At the dosage of 20μg/mL for 1-5, the glucose uptake increasing level was nearly 30%-40% in HepG2 cells. We partly revealed the glucose metabolism regulation effect may relate to dihydroflavonols in hollyhock flower.

  4. Flavin-containing monooxygenase-3: induction by 3-methylcholanthrene and complex regulation by xenobiotic chemicals in hepatoma cells and mouse liver.

    PubMed

    Celius, Trine; Pansoy, Andrea; Matthews, Jason; Okey, Allan B; Henderson, Marilyn C; Krueger, Sharon K; Williams, David E

    2010-08-15

    Flavin-containing monooxygenases often are thought not to be inducible but we recently demonstrated aryl hydrocarbon receptor (AHR)-dependent induction of FMO mRNAs in mouse liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Celius et al., Drug Metab Dispos 36:2499, 2008). We now evaluated FMO induction by other AHR ligands and xenobiotic chemicals in vivo and in mouse Hepa1c1c7 hepatoma cells (Hepa-1). In mouse liver, 3-methylcholanthrene (3MC) induced FMO3 mRNA 8-fold. In Hepa-1 cells, 3MC and benzo[a]pyrene (BaP) induced FMO3 mRNA >30-fold. Induction by 3MC and BaP was AHR dependent but, surprisingly, the potent AHR agonist, TCDD, did not induce FMO3 mRNA in Hepa-1 cells nor did chromatin immunoprecipitation assays detect recruitment of AHR or ARNT to Fmo3 regulatory elements after exposure to 3MC in liver or in Hepa-1 cells. However, in Hepa-1, 3MC and BaP (but not TCDD) caused recruitment of p53 protein to a p53 response element in the 5'-flanking region of the Fmo3 gene. We tested the possibility that FMO3 induction in Hepa-1 cells might be mediated by Nrf2/anti-oxidant response pathways, but agents known to activate Nrf2 or to induce oxidative stress did not affect FMO3 mRNA levels. The protein synthesis inhibitor, cycloheximide (which causes "superinduction" of CYP1A1 mRNA in TCDD-treated cells), by itself caused dramatic upregulation (>300-fold) of FMO3 mRNA in Hepa-1 suggesting that cycloheximide prevents synthesis of a labile protein that suppresses FMO3 expression. Although FMO3 mRNA is highly induced by 3MC or TCDD in mouse liver and in Hepa-1 cells, FMO protein levels and FMO catalytic function showed only modest elevation.

  5. Flavin-containing monooxygenase-3: Induction by 3-methylcholanthrene and complex regulation by xenobiotic chemicals in hepatoma cells and mouse liver

    SciTech Connect

    Celius, Trine; Pansoy, Andrea; Matthews, Jason; Okey, Allan B.; Henderson, Marilyn C.; Krueger, Sharon K.; Williams, David E.

    2010-08-15

    Flavin-containing monooxygenases often are thought not to be inducible but we recently demonstrated aryl hydrocarbon receptor (AHR)-dependent induction of FMO mRNAs in mouse liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Celius et al., Drug Metab Dispos 36:2499, 2008). We now evaluated FMO induction by other AHR ligands and xenobiotic chemicals in vivo and in mouse Hepa1c1c7 hepatoma cells (Hepa-1). In mouse liver, 3-methylcholanthrene (3MC) induced FMO3 mRNA 8-fold. In Hepa-1 cells, 3MC and benzo[a]pyrene (BaP) induced FMO3 mRNA > 30-fold. Induction by 3MC and BaP was AHR dependent but, surprisingly, the potent AHR agonist, TCDD, did not induce FMO3 mRNA in Hepa-1 cells nor did chromatin immunoprecipitation assays detect recruitment of AHR or ARNT to Fmo3 regulatory elements after exposure to 3MC in liver or in Hepa-1 cells. However, in Hepa-1, 3MC and BaP (but not TCDD) caused recruitment of p53 protein to a p53 response element in the 5'-flanking region of the Fmo3 gene. We tested the possibility that FMO3 induction in Hepa-1 cells might be mediated by Nrf2/anti-oxidant response pathways, but agents known to activate Nrf2 or to induce oxidative stress did not affect FMO3 mRNA levels. The protein synthesis inhibitor, cycloheximide (which causes 'superinduction' of CYP1A1 mRNA in TCDD-treated cells), by itself caused dramatic upregulation (> 300-fold) of FMO3 mRNA in Hepa-1 suggesting that cycloheximide prevents synthesis of a labile protein that suppresses FMO3 expression. Although FMO3 mRNA is highly induced by 3MC or TCDD in mouse liver and in Hepa-1 cells, FMO protein levels and FMO catalytic function showed only modest elevation.

  6. A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

    NASA Astrophysics Data System (ADS)

    Andersson, Patrik; McGuire, Jacqueline; Rubio, Carlos; Gradin, Katarina; Whitelaw, Murray L.; Pettersson, Sven; Hanberg, Annika; Poellinger, Lorenz

    2002-07-01

    The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated dioxins. Loss-of-function (gene-disruption) studies in mice have demonstrated that the AhR is involved in toxic effects of dioxins but have not yielded unequivocal results concerning the physiological function of the receptor. Gain-of-function studies therefore were performed to unravel the biological functions of the AhR. A constitutively active AhR expressed in transgenic mice reduced the life span of the mice and induced tumors in the glandular part of the stomach, demonstrating the oncogenic potential of the AhR and implicating the receptor in regulation of cell proliferation.

  7. A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

    PubMed Central

    Andersson, Patrik; McGuire, Jacqueline; Rubio, Carlos; Gradin, Katarina; Whitelaw, Murray L.; Pettersson, Sven; Hanberg, Annika; Poellinger, Lorenz

    2002-01-01

    The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated dioxins. Loss-of-function (gene-disruption) studies in mice have demonstrated that the AhR is involved in toxic effects of dioxins but have not yielded unequivocal results concerning the physiological function of the receptor. Gain-of-function studies therefore were performed to unravel the biological functions of the AhR. A constitutively active AhR expressed in transgenic mice reduced the life span of the mice and induced tumors in the glandular part of the stomach, demonstrating the oncogenic potential of the AhR and implicating the receptor in regulation of cell proliferation. PMID:12107286

  8. Hangman Catalysis for Photo- and Photoelectro- Chemical Activation of Water

    SciTech Connect

    Nocera, Daniel

    2014-04-15

    The focus of this DOE program is solar fuels – specifically the chemistry for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) from water and the oxygen reduction reaction (ORR) to water These three reactions are at the heart of renewable energy conversion. The bond-making and bond-breaking chemistry that underpins these transformations is not well understood. We are developing insight into such chemistry by creating a series of ligand constructs that poise an acid-base functionality over a redox active metal platform. These “hangman” ligands utilize the acid-base functionality to form a secondary coordination sphere that can assist proton movement and facilitate substrate assembly and activation within the molecular cleft. The grant period funding cycle focused on synthesis and reactivity of hangman porphyrins and corroles for HER, OER and ORR.

  9. Chemical Composition, Antifungal and Insecticidal Activities of Hedychium Essential Oils

    DTIC Science & Technology

    2013-04-11

    composition of the essential oils for the majority of the genotypes as well as their antifungal and insecticidal activities against the fungi C...essential oils were ineffective against the fungi Colletotrichum gloeosporioides, C. fragariae, and C. acutatum in this study, but essential oils...extracts against mycotoxigenic fungi . J. Crop Improv. 2012, 26, 389–396. Sample Availability: Contact the authors. © 2013 by the authors; licensee

  10. Hematite Surface Activation by Chemical Addition of Tin Oxide Layer.

    PubMed

    Carvalho, Waldemir M; Souza, Flavio L

    2016-09-05

    In this study, the effect of tin (Sn(4+) ) modification on the surface of hematite electrodes synthesized by an aqueous solution route at different times (2, 5, 10, 18, and 24 h) is investigated. As confirmed from X-ray diffraction results, the as-synthesized electrode exhibits an oxyhydroxide phase, which is converted into a pure hematite phase after being subjected to additional thermal treatment at 750 °C for 30 min. The tin-modified hematite electrode is prepared by depositing a solution of Sn(4+) precursor on the as-synthesized electrode, followed by thermal treatment under the same abovementioned conditions. This modification results in an enhancement of the photocurrent response for all hematite electrodes investigated and attains the highest values of around 1.62 and 2.3 mA cm(-2) at 1.23 and 1.4 V versus RHE, respectively, for electrodes obtained in short synthesis times (2 h). Contact angle measurements suggest that the deposition of Sn(4+) on the hematite electrode provides a more hydrophilic surface, which favors a chemical reaction at the interface between the electrode and electrolyte. This result generates new perspectives for understanding the deposition of Sn(4+) on the hematite electrode surface, which is in contrast with several studies previously reported; these studies state that the enhancement in photocurrent density is related to either the induction of an increased donor charge density or shift in the flat-band potential, which favors charge separation.

  11. X-ray imaging of chemically active valence electrons during a pericyclic reaction

    PubMed Central

    Bredtmann, Timm; Ivanov, Misha; Dixit, Gopal

    2014-01-01

    Time-resolved imaging of chemically active valence electron densities is a long-sought goal, as these electrons dictate the course of chemical reactions. However, X-ray scattering is always dominated by the core and inert valence electrons, making time-resolved X-ray imaging of chemically active valence electron densities extremely challenging. Here we demonstrate an effective and robust method, which emphasizes the information encoded in weakly scattered photons, to image chemically active valence electron densities. The degenerate Cope rearrangement of semibullvalene, a pericyclic reaction, is used as an example to visually illustrate our approach. Our work also provides experimental access to the long-standing problem of synchronous versus asynchronous bond formation and breaking during pericyclic reactions. PMID:25424639

  12. Collective dynamics of chemically active particles trapped at a fluid interface.

    PubMed

    Domínguez, Alvaro; Malgaretti, P; Popescu, M N; Dietrich, S

    2016-10-12

    Chemically active colloids generate changes in the chemical composition of their surrounding solution and thereby induce flows in the ambient fluid which affect their dynamical evolution. Here we study the many-body dynamics of a monolayer of spherically symmetric active particles trapped at a fluid-fluid interface. To this end we consider a model for the large-scale spatial distribution of particles which incorporates the direct pair interaction (including also the capillary interaction which is caused specifically by the interfacial trapping) as well as the effect of hydrodynamic interactions (including the Marangoni flow induced by the response of the interface to the chemical activity). The values of the relevant physical parameters for typical experimental realizations of such systems are estimated and various scenarios, which are predicted by our approach for the dynamics of the monolayer, are discussed. In particular, we show that the chemically-induced Marangoni flow can prevent the clustering instability driven by the capillary attraction.

  13. Immune activation affects chemical sexual ornaments of male Iberian wall lizards

    NASA Astrophysics Data System (ADS)

    López, Pilar; Gabirot, Marianne; Martín, José

    2009-01-01

    Many animals use chemical signals in sexual selection, but it is not clear how these sexual traits might have evolved to signal honestly male condition. It is possible that there is a trade-off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide), without pathogenic effects, to explore whether the immune activation affected chemical ornaments. Immune activation resulted in decreased proportions of a major chemical in femoral secretions (cholesta-5,7-dien-3-ol = provitamin D3) known to be selected in scent of males by females and which active form (vitamin D) has a variety of important effects on immune system function. This result suggests the existence of a potential trade-off between physiological regulation of the immune system and the allocation of essential nutrients (vitamins) to sexual chemical ornaments in male lizards.

  14. Prompt activation of telomerase by chemical carcinogens in rats detected with a modified TRAP assay.

    PubMed

    Miura, M; Karasaki, Y; Abe, T; Higashi, K; Ikemura, K; Gotoh, S

    1998-05-08

    The maintenance of telomere length is crucial for survival of cells. Telomerase is an RNA-containing reverse transcriptase, which is responsible for elongation of shortened telomeres. Telomerase reactivation has been suggested to be involved in malignant progressions. To study on the involvement of telomerase activation in in vivo carcinogenesis, we first modified the original TRAP assay by changing the primer designs and the labeling method of PCR products to an end-labeling method. Second, we investigated the activation of telomerase in different organs after treatments of rats with various chemical carcinogens. Very early after the beginning of the treatment, telomerase activity in the liver, kidney, and lung was increased. In most cases, telomerase activation occurred in the primary or favorite target organs. The present results suggest that telomerase activation occurs promptly when animals are exposed to chemical carcinogens, which may contribute to in vivo chemical carcinogenesis.

  15. Chemical composition and analgesic activity of Calophyllum brasiliense leaves.

    PubMed

    da Silva, K L; dos Santos, A R; Mattos, P E; Yunes, R A; Delle-Monache, F; Cechinel-Filho, V

    2001-01-01

    This paper describes a phytochemical and pharmacological study with Calophyllum brasiliense leaves, a medicinal plant employed in folk medicine for the treatment of several ailments. Based on spectroscopic evidence, five phenolic compounds were identified as hyperin (hyperoside), amentoflavone, quercetin, gallic acid, and protocatechuic acid. The fractions and some phenolic compounds exhibited significant analgesic activity against the writhing test and in relation to the second phase (inflammatory pain) of the formalin test in mice, suggesting that this plant can be useful for the treatment of dolorous processes.

  16. Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption.

    PubMed

    McMahon, George; Taylor, Amy E; Davey Smith, George; Munafò, Marcus R

    2014-01-01

    Two genetic loci, one in the cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) gene region (rs2472297) and one near the aryl-hydrocarbon receptor (AHR) gene (rs6968865), have been associated with habitual caffeine consumption. We sought to establish whether a more refined and comprehensive assessment of caffeine consumption would provide stronger evidence of association, and whether a combined allelic score comprising these two variants would further strengthen the association. We used data from between 4,460 and 7,520 women in the Avon Longitudinal Study of Parents and Children, a longitudinal birth cohort based in the United Kingdom. Self-report data on coffee, tea and cola consumption (including consumption of decaffeinated drinks) were available at multiple time points. Both genotypes were individually associated with total caffeine consumption, and with coffee and tea consumption. There was no association with cola consumption, possibly due to low levels of consumption in this sample. There was also no association with measures of decaffeinated drink consumption, indicating that the observed association is most likely mediated via caffeine. The association was strengthened when a combined allelic score was used, accounting for up to 1.28% of phenotypic variance. This was not associated with potential confounders of observational association. A combined allelic score accounts for sufficient phenotypic variance in caffeine consumption that this may be useful in Mendelian randomization studies. Future studies may therefore be able to use this combined allelic score to explore causal effects of habitual caffeine consumption on health outcomes.

  17. Chemical composition and antibacterial activity of Iranian Lavandula x hybrida.

    PubMed

    Bajalan, Iman; Rouzbahani, Razieh; Ghasemi Pirbalouti, Abdollah; Maggi, Filippo

    2017-03-17

    Lavandin (Lavandula x hybrida) is an evergreen shrub and cultivated worldwide for its essential oil which possesses various biological activities. In this study, the essential oils were isolated from the leaves of ten lavandin populations in western Iran. The hydrodistilled essential oils were analyzed by GC-FID/MS. Results indicated significant differences (p ≤0.05) among the various populations for the main essential oil constituents. The major components from different populations were 1,8-cineole (31.64 to 47.94%), borneol (17.11 to 26.14%), and camphor (8.41 to 12.68%). In vitro antibacterial activity was evaluated against S. agalactiae, S. aureus, E. coli and K. pneumoniae. The inhibition zones were in the range of 09.36 mm for S. aureus to 23.30 mm for E. coli. Results indicated that there was a significant correlation between essential oil composition and level of antibacterial efficacy expressed as inhibition zones. This article is protected by copyright. All rights reserved.

  18. Chemical constituents and biological activities of two Iranian Cystoseira species.

    PubMed

    Yegdaneh, Afsaneh; Ghannadi, Alireza; Dayani, Ladan

    2016-07-01

    The marine environment represents approximately half of the global biodiversity and could provide unlimited biological resources for the production of therapeutic drugs. Marine seaweeds comprise few thousands of species representing a considerable part of the littoral biomass. Extracts of the Cystoseira indica and Cystoseira merica were subjected to phytochemical and cytotoxicity evaluation. The amount of total phenol was determined with Folin-Ciocalteu reagent. Cytotoxicity was characterized by IC50 of human cancer cell lines including MCF-7 (human breast adenocarcinoma), HeLa (cervical carcinoma), and HT-29 (human colon adenocarcinoma) using Sulforhodamin assay. Antioxidant activities were evaluated using 2,2-diphenylpicrylhydrazyl (DPPH) method. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant constituents in these Cystoseira species while cyanogenic and cardiac glycosides were the least ones. C. indica had the higher content of total phenolics and also showed higher antioxidant activity. Cytotoxic results showed that both species inhibited cell growth effectively, especially against MCF-7 cell line. The present findings suggest potential pharmacological applications of selected seaweeds but require further investigation and identification of their bioactive principles.

  19. [Chemical constituents of Jasminum giraldii and their antioxidant activity].

    PubMed

    Zhang, Xiu-Peng; Qin, Hui; Yang, Fang; Chai, Jiang; Wang, Xin; Song, Xiao-Mei; Mei, Qi-Bing; Feng, Feng; Yue, Zheng-Gang

    2014-06-01

    Ten compounds were isolated from the barks of Jasminum giraldii by means of various of chromatographic techniques such as silica gel, Sephadex LH-20 and Rp-HPLC. Their structures were identified by spectroscopic data analysis as (+)-medioresinol (1), (+) -syringaresinol (2), syringaresinol-4'-O-beta-D-glucopyranoside (3), oleanic acid (4), 3-methoxy-4-hydroxy-trans-cinnamaldehyde (5), trans-sinapaldehyde (6), syringaldehyde (7), 1-(4-methoxy -phenyl) -ethanol (8), trans-cinnamic acid (9), and 4-(1-methoxyethyl) -phenol (10). Among them, compounds 1-3, 5-8 and 10 were isolated from the J. genus for the first time and compounds 4 and 9 were obtained from J. giraldii for the first time. In the DPPH free radical scavenging assay, compound 1 exhibited significant activity (IC50 55.1 micromol x L(-1)), compared with vitamin C(IC50 59.9 micromol x L(-1)); and compound 2 showed moderate activity (IC50 79.0 micromol x L(-1)), compared with 2, 6-di-tert-butyl4-methylphenol (IC50 236 micromol x L(-1)).

  20. Chemical constituents and biological activities of two Iranian Cystoseira species

    PubMed Central

    Yegdaneh, Afsaneh; Ghannadi, Alireza; Dayani, Ladan

    2016-01-01

    The marine environment represents approximately half of the global biodiversity and could provide unlimited biological resources for the production of therapeutic drugs. Marine seaweeds comprise few thousands of species representing a considerable part of the littoral biomass. Extracts of the Cystoseira indica and Cystoseira merica were subjected to phytochemical and cytotoxicity evaluation. The amount of total phenol was determined with Folin-Ciocalteu reagent. Cytotoxicity was characterized by IC50 of human cancer cell lines including MCF-7 (human breast adenocarcinoma), HeLa (cervical carcinoma), and HT-29 (human colon adenocarcinoma) using Sulforhodamin assay. Antioxidant activities were evaluated using 2,2-diphenylpicrylhydrazyl (DPPH) method. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant constituents in these Cystoseira species while cyanogenic and cardiac glycosides were the least ones. C. indica had the higher content of total phenolics and also showed higher antioxidant activity. Cytotoxic results showed that both species inhibited cell growth effectively, especially against MCF-7 cell line. The present findings suggest potential pharmacological applications of selected seaweeds but require further investigation and identification of their bioactive principles. PMID:27651811

  1. Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds.

    PubMed

    Salmina, Elena S; Haider, Norbert; Tetko, Igor V

    2015-12-23

    The article describes a classification system termed "extended functional groups" (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns and are available as part of the ToxAlerts tool (http://ochem.eu/alerts) of the On-line CHEmical database and Modeling (OCHEM) environment platform. The article describes the motivation and the main ideas behind this extension and demonstrates that EFG can be efficiently used to develop and interpret structure-activity relationship models.

  2. Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization.

    PubMed

    Cimmino, Alessio; Masi, Marco; Evidente, Marco; Superchi, Stefano; Evidente, Antonio

    2015-12-19

    Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites.

  3. Chemical constituents and antioxidant activity of Mallotus roxburghianus leaves.

    PubMed

    Rana, Virendra S; Rawat, Mohan S M; Pant, Geeta; Nagatsu, Akito

    2005-06-01

    Mallotus roxburghianus is used in the traditional medicine in North-Eastern India, but previously no work has been done on the identification of bioactive compounds. Two new compounds, 3-(1-C-beta-D-glucopyranosyl)-2,6-dihydroxy-5-methoxybenzoic acid (6) and 2,4,8,9,10-pentahydroxy-3,7-dimethoxyanthracene-6-O-beta-D-rhamnopyranoside (7) together with beta-sitosterol (1), stigmasterol (2), betulinic acid (3), 4-hydroxybenzoic acid (4), beta-sitosterol-beta-D-glucoside (5), and bergenin (8) were isolated and identified from the leaves of M. roxburghianus. The chloroform soluble portion of the alcoholic extract of leaf, and compounds 3, 6, 7, and 8 exhibited encouraging antioxidant activities.

  4. Estrogenic activity of chemical constituents from Tephrosia candida.

    PubMed

    Hegazy, Mohamed-Elamir F; El-Hamd H Mohamed, Abou; El-Halawany, Ali M; Djemgou, Pierre C; Shahat, Abdelaaty A; Paré, Paul W

    2011-05-27

    In a continued investigation of medicinal plants from the genus Tephrosia, phytochemical analysis of a methylene chloride-methanol (1:1) extract of the air-dried aerial parts of Tephrosia candida afforded two new 8-prenylated flavonoids, namely, tephrocandidins A (1) and B (2), a new prenylated chalcone, candidachalcone (3), a new sesquiterpene (4), and a previously reported pea flavonoid phytoalexin, pisatin (5). The structures of 1-4 were established by spectroscopic methods, including HREIMS, and 1H, 13C, DEPT, HMQC, and HMBC NMR experiments. The most potent estrogenic activity of these isolated natural products in an estrogen receptor (ERα) competitive-binding assay was for 3, which exhibited an IC50 value of 80 μM, compared with 18 nM for the natural steroid 17β-estradiol. Results were interpreted via virtual docking of isolated compounds to an ERα crystal structure.

  5. Elucidating Mechanisms of Toxicity Using Phenotypic Data from Primary Human Cell Systems—A Chemical Biology Approach for Thrombosis-Related Side Effects

    PubMed Central

    Berg, Ellen L.; Polokoff, Mark A.; O’Mahony, Alison; Nguyen, Dat; Li, Xitong

    2015-01-01

    Here we describe a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects. This work takes advantage of a large chemical biology data set comprising the effects of known, well-characterized reference agents on the cell surface levels of tissue factor (TF) in a primary human endothelial cell-based model of vascular inflammation, the BioMAP® 3C system. In previous work with the Environmental Protection Agency (EPA) for the ToxCast™ program, aryl hydrocarbon receptor (AhR) agonists and estrogen receptor (ER) antagonists were found to share an usual activity, that of increasing TF levels in this system. Since human exposure to compounds in both chemical classes is associated with increased incidence of thrombosis-related side effects, we expanded this analysis with a large number of well-characterized reference compounds in order to better understand the underlying mechanisms. As a result, mechanisms for increasing (AhR, histamine H1 receptor, histone deacetylase or HDAC, hsp90, nuclear factor kappa B or NFκB, MEK, oncostatin M receptor, Jak kinase, and p38 MAPK) and decreasing (vacuolar ATPase or V-ATPase) and mTOR) TF expression levels were uncovered. These data identify the nutrient, lipid, bacterial, and hypoxia sensing functions of autophagy as potential key regulatory points controlling cell surface TF levels in endothelial cells and support the mechanistic hypothesis that these functions are associated with thrombosis-related side effects in vivo. PMID:25569083

  6. Polysaccharides from Arctium lappa L.: Chemical structure and biological activity.

    PubMed

    Carlotto, Juliane; de Souza, Lauro M; Baggio, Cristiane H; Werner, Maria Fernanda de P; Maria-Ferreira, Daniele; Sassaki, Guilherme L; Iacomini, Marcello; Cipriani, Thales R

    2016-10-01

    The plant Arctium lappa L. is popularly used to relieve symptoms of inflammatory disorders. A crude polysaccharide fraction (SAA) resulting of aqueous extraction of A. lappa leaves showed a dose dependent anti-edematogenic activity on carrageenan-induced paw edema, which persisted for up to 48h. Sequential fractionation by ultrafiltration at 50kDa and 30kDa cut-off membranes yielded three fractions, namely RF50, RF30, and EF30. All these maintained the anti-edematogenic effect, but RF30 showed a more potent action, inhibiting 57% of the paw edema at a dose of 4.9mg/kg. The polysaccharide RF30 contained galacturonic acid, galactose, arabinose, rhamnose, glucose, and mannose in a 7:4:2:1:2:1 ratio and had a Mw of 91,000g/mol. Methylation analysis and NMR spectroscopy indicated that RF30 is mainly constituted by a type I rhamnogalacturonan branched by side chains of types I and II arabinogalactans, and arabinan.

  7. CO2 adsorption on chemically modified activated carbon.

    PubMed

    Caglayan, Burcu Selen; Aksoylu, A Erhan

    2013-05-15

    CO2 adsorption capacity of a commercial activated carbon was improved by using HNO3 oxidation, air oxidation, alkali impregnation and heat treatment under helium gas atmosphere. The surface functional groups produced were investigated by diffuse reflectance infrared Fourier transform spectrometer (DRIFTS). CO2 adsorption capacities of the samples were determined by gravimetric analyses for 25-200°C temperature range. DRIFTS studies revealed the formation of carboxylic acid groups on the HNO3 oxidized adsorbents. Increased aromatization and uniform distribution of the Na particles were observed on the samples prepared by Na2CO3 impregnation onto HNO3 oxidized AC support. The adsorption capacities of the nonimpregnated samples were increased by high temperature helium treatments or by increasing the adsorption temperature; both leading to decomposition of surface oxygen groups, forming sites that can easily adsorb CO2. The adsorption capacity loss due to cyclic adsorption/desorption procedures was overcome with further surface stabilization of Na2CO3 modified samples with high temperature He treatments. With Na2CO3 impregnation the mass uptakes of the adsorbents at 20 bars and 25 °C were improved by 8 and 7 folds and at 1 bar were increased 15 and 16 folds, on the average, compared to their air oxidized and nitric acid oxidized supports, respectively.

  8. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A.

    PubMed

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J; Komai, Michio

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein-protein interactions with GR.

  9. The effects of activation temperature on physico-chemical characteristics of activated carbons derived from biomass wastes

    NASA Astrophysics Data System (ADS)

    Sutrisno, Bachrun; Hidayat, Arif

    2015-12-01

    This research focused on investigating in the effect of activation temperature on the physico-chemical properties of palm empty fruit bunch (PEFB) based activated carbon prepared by physical activation with carbon dioxide. The activation temperature was studied in the range of 400-800°C by keeping the activation temperature at 800°C for 120 min. It was found that the porous properties of activated carbon decreased with an increase in carbonization temperature. The activated carbons prepared at the highest activation temperature at 800°C and activation time of 120 min gave the activated carbon with the highest of BET surface area and pore volume of 938 m2/g and 0.4502 cm3/g, respectively

  10. Using Laboratory Chemicals to Imitate Illicit Drugs in a Forensic Chemistry Activity

    ERIC Educational Resources Information Center

    Hasan, Shawn; Bromfield-Lee, Deborah; Oliver-Hoyo, Maria T.; Cintron-Maldonado, Jose A.

    2008-01-01

    This forensic chemistry activity utilizes presumptive forensic testing procedures and laboratory chemicals that produce screening results similar to controlled substances. For obvious reasons, obtaining heavily regulated controlled substances to create an undergraduate student activity is not practical for most educational institutions. We were…

  11. CHARACTERIZATION OF ACTIVATED CARBONS' PHYSICAL AND CHEMICAL PROPERTIES IN RELATION TO THEIR MERCURY ADSORPTION

    EPA Science Inventory

    The paper gives results of a characterization of the physical and chemical properties of the activated carbons used for elemental mercury (Hgo) adsorption, in order to understand the role of oxygen surface functional groups on the mechanism of Hgo adsorption by activated carbons....

  12. Chemical proteomic probes for profiling cytochrome P450 activities and drug interactions in vivo

    PubMed Central

    Wright, Aaron T.; Cravatt, Benjamin F.

    2007-01-01

    The cytochrome P450 (P450) superfamily metabolizes many endogenous signaling molecules and drugs. P450 enzymes are regulated by post-translational mechanisms in vivo, which hinders their functional characterization by conventional genomic or proteomic methods. Here, we describe a chemical proteomic strategy to profile P450 activities directly in living systems. Derivatization of a mechanism-based inhibitor with a “clickable” handle provided an activity-based probe that labels multiple P450s both in proteomic extracts and in vivo. This probe was used to record alterations in liver P450 activities triggered by chemical agents, including inducers of P450 expression and direct P450 inhibitors. The chemical proteomic strategy described herein thus offers a versatile method to monitor P450 activities and small molecule interactions in any biological system and, through doing so, should facilitate the functional characterization of this large and diverse enzyme class. PMID:17884636

  13. Cloud Condensation Nuclei Activity Associated with Chemical Composition and Precipitation Events

    NASA Astrophysics Data System (ADS)

    Corrigan, C.; Roberts, G. C.; Zauscher, M.; Suski, K.; Noblitts, S.; Sullivan, A. P.; Collett, J. L.

    2010-12-01

    Measurements of ambient cloud condensation nuclei (CCN) concentrations can be improved by simultaneously collecting information on the activation size of the CCN along with chemical composition of the ambient aerosol. A size scanning CCN instrument developed at Scripps Institution of Oceanography was deployed as part of the Calwater project in the Sierra Nevada foothills of California during February and March of 2010. The instrument was capable of determining the critical diameter of activation for the ambient aerosol during a 20 minute scan. During the study period, the CCN activation size increased after each rain event and the activity slowly returned over the next few days. The critical diameter of the overall aerosol was largest (least active) immediately following precipitation events. The average critical diameter would typically decrease by 20% in the time between major precipitation events. This regeneration of the CCN activity can be partially attributed to the transport of sulfate and nitrate pollution to replace the particles that were washed out by the rain, but it may also be due to chemical changes via aging and oxidation mechanisms. Since CCN activity is determined by the particles size and chemical composition, the changes in critical diameter indicate a change in the chemical composition of the available CCN particles. By comparing the critical diameters with aerosol chemical data from a semi-real time aerosol ion chromatograph, the CCN activity was generally correlated with the mass loading of sulfate and nitrate. Deviations from the expected activity of sulfate and nitrate indicate the existence of other compounds that contribute to activity through additional dissolution and by reducing the surface tension. The contribution to CCN activity from additional compounds, including organic surfactants, can be estimated by observing the deviation of the measured critical diameters from values calculated using only the measured nitrate+sulfate mass

  14. Structure-activity comparison of hydrazine to other Nasotoxic chemicals. Final report, August-October 1991

    SciTech Connect

    Godin, C.S.; Wall, H.G.

    1992-08-01

    The biotransformation of 19 chemicals that have caused nasal epithelial toxicity in-long-term carcinogenesis experiments in laboratory rodents was compared with the biotransformation of hydrazine, in order to determine if these chemicals share common metabolic pathways. Ten of the 19 chemicals were tumorigenic; four were epoxides or epoxide-formers; three were metabolized to reactive aldehydes; and one was metabolized to a lactone ring. The two remaining chemicals, p-cresidene and 2,6-xylidene, possess an amino group that can undergo biotransformation to reactive metabolites in a way similar to hydrazine, but there is no evidence to support this hypothesis. Therefore, none of the 19 chemicals are metabolized in a way similar to hydrazine.... Structure-activity, Hydrazine, Nasotoxicity, Carcinogenicity.

  15. Chemically active colloids near osmotic-responsive walls with surface-chemistry gradients

    NASA Astrophysics Data System (ADS)

    Popescu, M. N.; Uspal, W. E.; Dietrich, S.

    2017-04-01

    Chemically active colloids move by creating gradients in the composition of the surrounding solution and by exploiting the differences in their interactions with the various molecular species in solution. If such particles move near boundaries, e.g. the walls of the container confining the suspension, gradients in the composition of the solution are also created along the wall. This give rise to chemi-osmosis (via the interactions of the wall with the molecular species forming the solution), which drives flows coupling back to the colloid and thus influences its motility. Employing an approximate ‘point-particle’ analysis, we show analytically that—owing to this kind of induced active response (chemi-osmosis) of the wall—such chemically active colloids can align with, and follow, gradients in the surface chemistry of the wall. In this sense, these artificial ‘swimmers’ exhibit a primitive form of thigmotaxis with the meaning of sensing the proximity of a (not necessarily discontinuous) physical change in the environment. We show that the alignment with the surface-chemistry gradient is generic for chemically active colloids as long as they exhibit motility in an unbounded fluid, i.e. this phenomenon does not depend on the exact details of the propulsion mechanism. The results are discussed in the context of simple models of chemical activity, corresponding to Janus particles with ‘source’ chemical reactions on one half of the surface and either ‘inert’ or ‘sink’ reactions over the other half.

  16. Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets.

    PubMed

    Knudsen, Thomas B; Houck, Keith A; Sipes, Nisha S; Singh, Amar V; Judson, Richard S; Martin, Matthew T; Weissman, Arthur; Kleinstreuer, Nicole C; Mortensen, Holly M; Reif, David M; Rabinowitz, James R; Setzer, R Woodrow; Richard, Ann M; Dix, David J; Kavlock, Robert J

    2011-03-28

    Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The present study is a performance evaluation and critical analysis of assay results for an array of 292 high-throughput cell-free assays aimed at preliminary toxicity evaluation of 320 environmental chemicals in EPA's ToxCast™ project (Phase I). The chemicals (309 unique, 11 replicates) were mainly precursors or the active agent of commercial pesticides, for which a wealth of in vivo toxicity data is available. Biochemical HTS (high-throughput screening) profiled cell and tissue extracts using semi-automated biochemical and pharmacological methodologies to evaluate a subset of G-protein coupled receptors (GPCRs), CYP450 enzymes (CYPs), kinases, phosphatases, proteases, HDACs, nuclear receptors, ion channels, and transporters. The primary screen tested all chemicals at a relatively high concentration 25 μM concentration (or 10 μM for CYP assays), and a secondary screen re-tested 9132 chemical-assay pairs in 8-point concentration series from 0.023 to 50 μM (or 0.009-20 μM for CYPs). Mapping relationships across 93,440 chemical-assay pairs based on half-maximal activity concentration (AC50) revealed both known and novel targets in signaling and metabolic pathways. The primary dataset, summary data and details on quality control checks are available for download at http://www.epa.gov/ncct/toxcast/.

  17. Structural features of endocrine active chemicals--A comparison of in vivo and in vitro data.

    PubMed

    Lewin, Geertje; Escher, Sylvia E; van der Burg, Bart; Simetska, Nelly; Mangelsdorf, Inge

    2015-08-01

    Studies on reproductive toxicity need high numbers of test animals. Therefore, we investigated whether chemical structural features (SF) in combination with in vitro data on specific adverse outcome pathways (AOPs) may be used for predicting reproductive toxicity of untested chemicals. Using the OECD Toolbox and expert judgment, we identified 89 structure groups for 275 chemicals for which the results of prenatal developmental toxicity or multigeneration studies were present in the Fraunhofer database on Fertility and Developmental Toxicity in experimental animals (FeDTex) database. Likewise, we evaluated 220 chemicals which had been tested in reporter gene assays on endocrine ((anti)estrogenic and (anti)androgenic) properties in the CALUX(®) test battery. There was a large spread of effect levels for substances within the chemical structure groups for both, in vivo and in vitro results. The groups of highest concern (diphenyl derivatives, planar conjugated systems with fused rings, phenols and organophosphates) correlated quite well, however, between the in vivo and in vitro data on estrogenic activity. For the 56 chemicals represented in both databases, lowest effect doses in vivo correlated well with the estrogenic activity in vitro. These results suggest that a panel of assays covering relevant AOPs and data on metabolism and toxicokinetics may allow prediction of relative reproductive or development toxicity potency within the identified chemical structure groups.

  18. Fault Diagnosis Based on Chemical Sensor Data with an Active Deep Neural Network.

    PubMed

    Jiang, Peng; Hu, Zhixin; Liu, Jun; Yu, Shanen; Wu, Feng

    2016-10-13

    Big sensor data provide significant potential for chemical fault diagnosis, which involves the baseline values of security, stability and reliability in chemical processes. A deep neural network (DNN) with novel active learning for inducing chemical fault diagnosis is presented in this study. It is a method using large amount of chemical sensor data, which is a combination of deep learning and active learning criterion to target the difficulty of consecutive fault diagnosis. DNN with deep architectures, instead of shallow ones, could be developed through deep learning to learn a suitable feature representation from raw sensor data in an unsupervised manner using stacked denoising auto-encoder (SDAE) and work through a layer-by-layer successive learning process. The features are added to the top Softmax regression layer to construct the discriminative fault characteristics for diagnosis in a supervised manner. Considering the expensive and time consuming labeling of sensor data in chemical applications, in contrast to the available methods, we employ a novel active learning criterion for the particularity of chemical processes, which is a combination of Best vs. Second Best criterion (BvSB) and a Lowest False Positive criterion (LFP), for further fine-tuning of diagnosis model in an active manner rather than passive manner. That is, we allow models to rank the most informative sensor data to be labeled for updating the DNN parameters during the interaction phase. The effectiveness of the proposed method is validated in two well-known industrial datasets. Results indicate that the proposed method can obtain superior diagnosis accuracy and provide significant performance improvement in accuracy and false positive rate with less labeled chemical sensor data by further active learning compared with existing methods.

  19. Fault Diagnosis Based on Chemical Sensor Data with an Active Deep Neural Network

    PubMed Central

    Jiang, Peng; Hu, Zhixin; Liu, Jun; Yu, Shanen; Wu, Feng

    2016-01-01

    Big sensor data provide significant potential for chemical fault diagnosis, which involves the baseline values of security, stability and reliability in chemical processes. A deep neural network (DNN) with novel active learning for inducing chemical fault diagnosis is presented in this study. It is a method using large amount of chemical sensor data, which is a combination of deep learning and active learning criterion to target the difficulty of consecutive fault diagnosis. DNN with deep architectures, instead of shallow ones, could be developed through deep learning to learn a suitable feature representation from raw sensor data in an unsupervised manner using stacked denoising auto-encoder (SDAE) and work through a layer-by-layer successive learning process. The features are added to the top Softmax regression layer to construct the discriminative fault characteristics for diagnosis in a supervised manner. Considering the expensive and time consuming labeling of sensor data in chemical applications, in contrast to the available methods, we employ a novel active learning criterion for the particularity of chemical processes, which is a combination of Best vs. Second Best criterion (BvSB) and a Lowest False Positive criterion (LFP), for further fine-tuning of diagnosis model in an active manner rather than passive manner. That is, we allow models to rank the most informative sensor data to be labeled for updating the DNN parameters during the interaction phase. The effectiveness of the proposed method is validated in two well-known industrial datasets. Results indicate that the proposed method can obtain superior diagnosis accuracy and provide significant performance improvement in accuracy and false positive rate with less labeled chemical sensor data by further active learning compared with existing methods. PMID:27754386

  20. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  1. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  2. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  3. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  4. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  5. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha.

    PubMed

    Abdelrahim, Maen; Ariazi, Eric; Kim, Kyounghyun; Khan, Shaheen; Barhoumi, Rola; Burghardt, Robert; Liu, Shengxi; Hill, Denise; Finnell, Richard; Wlodarczyk, Bogdan; Jordan, V Craig; Safe, Stephen

    2006-02-15

    3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ER alpha but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ER alpha, and this was confirmed in a competitive ER alpha binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ER alpha/YFP-ER alpha interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ER alpha (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha.

  6. Analysis of essential oils from Voacanga africana seeds at different hydrodistillation extraction stages: chemical composition, antioxidant activity and antimicrobial activity.

    PubMed

    Liu, Xiong; Yang, Dongliang; Liu, Jiajia; Ren, Na

    2015-01-01

    In this study, essential oils from Voacanga africana seeds at different extraction stages were investigated. In the chemical composition analysis, 27 compounds representing 86.69-95.03% of the total essential oils were identified and quantified. The main constituents in essential oils were terpenoids, alcohols and fatty acids accounting for 15.03-24.36%, 21.57-34.43% and 33.06-57.37%, respectively. Moreover, the analysis also revealed that essential oils from different extraction stages possessed different chemical compositions. In the antioxidant evaluation, all analysed oils showed similar antioxidant behaviours, and the concentrations of essential oils providing 50% inhibition of DPPH-scavenging activity (IC50) were about 25 mg/mL. In the antimicrobial experiments, essential oils from different extraction stages exhibited different antimicrobial activities. The antimicrobial activity of oils was affected by extraction stages. By controlling extraction stages, it is promising to obtain essential oils with desired antimicrobial activities.

  7. Anti-arthritic active fraction of Capparis spinosa L. fruits and its chemical constituents.

    PubMed

    Feng, Xiaolu; Lu, Jincai; Xin, Hailiang; Zhang, Lei; Wang, Yuliang; Tang, Kexuan

    2011-03-01

    The aim of this study was to ascertain the anti-arthritic active fraction of Capparis spinosa L. (Capparidaceae) fruits and its chemical constituents. The adjuvant arthritic rat model was developed to evaluate the anti-arthritic effects of different fractions of ethanol extraction from C. spinosa L. The fraction eluted by ethanol-water (50:50, v/v) had the most significant anti-arthritic activity. The chemical constituents of this fraction were therefore studied; seven known compounds were isolated and identified as: P-hydroxy benzoic acid; 5-(hydroxymethyl) furfural; bis(5-formylfurfuryl) ether; daucosterol; α-D-fructofuranosides methyl; uracil; and stachydrine.

  8. Numerical investigation of oscillatory multiphase flow in porous medium with chemically active skeleton

    NASA Astrophysics Data System (ADS)

    Konyukhov, A. V.; Zavialov, I. N.

    2016-11-01

    Self-oscillating mode of reaction front propagation in multiphase flow in the porous medium with chemically active skeleton is investigated numerically. The considered flow represents an immiscible displacement process, such that the displacing fluid and the skeleton of the porous medium have chemically active components which react with production of gaseous phase. The calculations have demonstrated strong influence of the reaction kinetics on stability of the reactive flow. The presence of a time delay between the change of concentration of the reactants and the change of the reaction rate is shown to stimulate transition of the reaction front propagation to the oscillatory mode.

  9. A Global Genomic Screening Strategy Reveals Genetic and Chemical Activators ofPeroxisome Proliferator-Activated Receptor alpha (PPARalpha)

    EPA Science Inventory

    A comprehensive survey of chemical, diet and genetic perturbations that activate PPARalpha in the mouse liver has not been carried out but would be useful to identify the factors that may contribute to PPARalpha-dependent liver tumors. A gene signature dependent on PPARalpha ac...

  10. Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol.

    PubMed

    Mazan, Melissa R; Lascola, Kara; Bruns, Susan J; Hoffman, Andrew M

    2014-07-01

    Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challenge test. The percentage of radio-aerosol deposited in the total lung was 12.39% ± 5.05%. All study horses demonstrated airway hyperresponsiveness (AHR) before enrollment in the study [mean provocative concentration eliciting 35% increase in delta flow (PC35) < 6 mg/mL histamine]. There was no significant difference in airway hyperresponsiveness to post-albuterol histamine challenge before or after treatment with albuterol. A 10-d treatment with placebo, however, caused a significant increase in airway hyperresponsiveness in all horses (P < 0.001). The results of this study show that the novel mask-spacer device was effective in delivering radiolabeled aerosolized drug to the lung and that delivery of a SABA for 10 d using this device did not result in increased airway hyperresponsiveness.

  11. Gamma irradiation effect on the chemical composition and the antioxidant activity of Ipomoea batatas L

    SciTech Connect

    Tahir, D. Halide, H. Kurniawan, D.; Wahab, A. W.

    2014-09-25

    The chemical composition and antioxidant activity of Ipomoea batatas L. (sweet potato) were studied by x-ray fluorescence (XRF) spectroscopy, Fourier transform infrared spectroscopy, and by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity. The irradiation treatment was performed by using Cs-137 as a gamma sources in experimental equipment. Treatment by irradiation emerges as a possible conservation technique that has been tested successfully in several food products. The amount of chemical composition was changed and resulting new chemical for absorbed dose 40 mSv. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by DPPH radical scavenging capacity. The antioxidant activity of Ipomoea batatas L. extract was dramatically increased in the non-irradiated sample to the sample irradiated at 40 mSv. These results indicate that gamma irradiation of Ipomoea batatas L. extract can enhance its antioxidant activity through the formation of a new chemical compound. Based on these results, increased antioxidant activity of Ipomoea batatas L. extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  12. Gamma irradiation effect on the chemical composition and the antioxidant activity of Ipomoea batatas L.

    NASA Astrophysics Data System (ADS)

    Tahir, D.; Halide, H.; Wahab, A. W.; Kurniawan, D.

    2014-09-01

    The chemical composition and antioxidant activity of Ipomoea batatas L. (sweet potato) were studied by x-ray fluorescence (XRF) spectroscopy, Fourier transform infrared spectroscopy, and by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity. The irradiation treatment was performed by using Cs-137 as a gamma sources in experimental equipment. Treatment by irradiation emerges as a possible conservation technique that has been tested successfully in several food products. The amount of chemical composition was changed and resulting new chemical for absorbed dose 40 mSv. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by DPPH radical scavenging capacity. The antioxidant activity of Ipomoea batatas L. extract was dramatically increased in the non-irradiated sample to the sample irradiated at 40 mSv. These results indicate that gamma irradiation of Ipomoea batatas L. extract can enhance its antioxidant activity through the formation of a new chemical compound. Based on these results, increased antioxidant activity of Ipomoea batatas L. extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  13. ADHESIVES WITH DIFFERENT PHS: EFFECT ON THE MTBS OF CHEMICALLY ACTIVATED AND LIGHT-ACTIVATED COMPOSITES TO HUMAN DENTIN

    PubMed Central

    Mallmann, André; de Melo, Renata Marques; Estrela, Verbênia; Pelogia, Fernanda; Campos, Laura; Bottino, Marco Antonio; Valandro, Luiz Felipe

    2007-01-01

    Purpose: To evaluate the bond strength between human dentin and composites, using two light-activated single-bottle total-etch adhesive systems with different pHs combined with chemically activated and light-activated-composites. The tested hypothesis was that the dentin bond strength is not influenced by an adhesive system of low pH, combined with chemically activated or light-activated composites. Material and Method: Flat dentin surfaces of twenty-eight human third molars were allocated in 4 groups (n=7), depending on the adhesive system: (One Step Plus-OS and Prime & Bond NT-PB) and composite (light-activated Filtek Z-100 [Z100] and chemically activated Bisfil 2B [B2B]). Each adhesive system was applied on acid-etched dentin and then one of the composites was added to form a 5 mm-high resin block. The specimens were stored in tap water (37°C/24 h) and sectioned into two axes, x and y. This was done with a diamond disk under coolant irrigation to obtain beams with a cross-section area of approximately 0.8 mm2. Each specimen was then attached to a custom-made device and submitted to the microtensile test (1 mm.min−1). Data were analyzed using two-way ANOVA and Tukey’s tests (p<0.05). Results: The anticipated hypothesis was not confirmed (p<0.0001). The bond strengths (MPa) were not statistically different between the two adhesive systems when light-activated composite was used (OS+Z100 = 24.7±7.1ª; PB+Z100 = 23.8±5.7ª). However, with use of the chemically activated composite (B2B), PB (7.8±3.6b MPa) showed significantly lower dentin bond strengths than OS (32.2±7.6ª). Conclusion: The low pH of the adhesive system can affect the bond of chemically activated composite to dentin. On the other hand, under the present conditions, the low pH did not seem to affect the bond of light-activated composites to dentin significantly. PMID:19089142

  14. Essential Oil Composition of Phagnalon sordidum (L.) from Corsica, Chemical Variability and Antimicrobial Activity.

    PubMed

    Brunel, Marion; Vitrac, Caroline; Costa, Jean; Mzali, Fatima; Vitrac, Xavier; Muselli, Alain

    2016-03-01

    The chemical composition of Phagnalon sordidum (L.) essential oil was investigated for the first time using gas chromatography and chromatography/mass spectrometry. Seventy-six compounds, which accounted for 87.9% of the total amount, were identified in a collective essential oil of P. sordidum from Corsica. The main essential oil components were (E)-β-caryophyllene (14.4%), β-pinene (11.0%), thymol (9.0%), and hexadecanoic acid (5.3%). The chemical compositions of essential oils from 19 Corsican locations were investigated. The study of the chemical variability using statistical analysis allowed identifying direct correlation between the three populations of P. sordidum widespread in Corsica and the essential oil compositions they produce. The in vitro antimicrobial activity of P. sordidum essential oil was evaluated and it exhibited a notable activity on a large panel of clinically significant microorganisms.

  15. Computer-assisted mechanistic structure-activity studies: application to diverse classes of chemical carcinogens.

    PubMed Central

    Loew, G H; Poulsen, M; Kirkjian, E; Ferrell, J; Sudhindra, B S; Rebagliati, M

    1985-01-01

    In the first part of this paper we have indicated how the techniques and capabilities of theoretical chemistry, together with experimental results, can be used in a mechanistic approach to structure-activity studies of toxicity. In the second part, we have illustrated how this computer-assisted approach has been used to identify and calculate causally related molecular indicators of relative carcinogenic activity in five classes of chemical carcinogens: polycyclic aromatic hydrocarbons and their methyl derivatives, aromatic amines, chloroethanes, chloroalkenes and dialkyl nitrosamines. In each class of chemicals studied, candidate molecular indicators have been identified that could be useful in predictive screening of unknown compounds. In addition, further insights into some mechanistic aspects of chemical carcinogenesis have been obtained. Finally, experiments have been suggested to both verify the usefulness of the indicators and test their mechanistic implications. PMID:3905382

  16. C15078. Essential oil composition of Phagnalon sordidum (L.) from Corsica, chemical variability and antimicrobial activity.

    PubMed

    Brunel, Marion; Vitrac, Caroline; Costa, Jean; Mzali, Fatima; Vitrac, Xavier; Muselli, Alain

    2016-02-10

    The chemical composition of Phagnalon sordidum (L.) essential oil was investigated for the first time using gas chromatography and chromatography-mass spectrometry. Seventy-six compounds, which accounted for 87.9% of the total amount, were identified in a collective essential oil of P. sordidum from Corsica. The main essential oil components were (E)-β-caryophyllene (14.4%), β-pinene (11.0%), thymol (9.0%), and hexadecanoic acid (5.3%). The chemical compositions of essential oils from 19 Corsican locations were investigated. The study of the chemical variability using statistical analysis allowed identifying direct correlation between the three populations of P. sordidum widespread in Corsica and the essential oil compositions they produce. The in vitro antimicrobial activity of P. sordidum essential oil was evaluated and exhibited a notable activity on a large panel of clinically significant microorganisms. This article is protected by copyright. All rights reserved.

  17. Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities.

    PubMed

    Ferreira, Isabel C F R; Heleno, Sandrina A; Reis, Filipa S; Stojkovic, Dejan; Queiroz, Maria João R P; Vasconcelos, M Helena; Sokovic, Marina

    2015-06-01

    Ganoderma genus comprises one of the most commonly studied species worldwide, Ganoderma lucidum. However, other Ganoderma species have been also reported as important sources of bioactive compounds. Polysaccharides are important contributors to the medicinal properties reported for Ganoderma species, as demonstrated by the numerous publications, including reviews, on this matter. Yet, what are the chemical features of Ganoderma polysaccharides that have bioactivity? In the present manuscript, the chemical features of Ganoderma polysaccharides with reported antioxidant, antitumor and antimicrobial activities (the most studied worldwide) are analyzed in detail. The composition of sugars (homo- versus hetero-glucans and other polysaccharides), type of glycosidic linkages, branching patterns, and linkage to proteins are discussed. Methods for extraction, isolation and identification are evaluated and, finally, the bioactivity of polysaccharidic extracts and purified compounds are discussed. The integration of data allows deduction of structure-activity relationships and gives clues to the chemical aspects involved in Ganoderma bioactivity.

  18. Structure-activity relations between alkyl nucleophilic chemicals causing duodenal ulcer and adrenocortical necrosis

    SciTech Connect

    Szabo, S.; Reynolds, E.S.; Unger, S.H.

    1982-10-01

    Structure-activity relationships were qualitatively and quantitatively examined for 56 chemicals (e.g., derivatives of propionitrile, acrylonitrile and cysteamine) which caused duodenal ulcer and/or adrenocortical necrosis in rats. For the first time the duodenal ulcerogenic property of numerous chemicals has been studied in a rational and predictive manner. Ulcerogenic activity was most intense in the carbonitriles attached to two or three carbon backbones and diminished by shortening, lengthening, branching, unsaturating, halogenating or hydroxylating the carbon chains. Different modes of action are implied. Adrenocorticolytic potency was associated with unsaturation of the carbon chain and substitution of the nitrile by thiol or amine radicals. An action of these chemicals on the central nervous system has been suggested.

  19. Idaho Chemical Processing Plant low-activity waste grout stabilization development program FY-97 status report

    SciTech Connect

    Herbst, A.K.; Marshall, D.W.; McCray, J.A.

    1998-02-01

    The general purpose of the Grout Development Program is to solidify and stabilize the liquid low-activity wastes (LAW) generated at the Idaho Chemical Processing Plant (ICPP). It is anticipated that LAW will be produced from the following: (1) chemical separation of the tank farm high-activity sodium-bearing waste, (2) retrieval, dissolution, and chemical separation of the aluminum, zirconium, and sodium calcines, (3) facility decontamination processes, and (4) process equipment waste. Grout formulation studies for sodium-bearing LAW, including decontamination and process equipment waste, continued this fiscal year. A second task was to develop a grout formulation to solidify potential process residual heels in the tank farm vessels when the vessels are closed.

  20. Estimating Air Chemical Emissions from Research Activities Using Stack Measurement Data

    SciTech Connect

    Ballinger, Marcel Y.; Duchsherer, Cheryl J.; Woodruff, Rodger K.; Larson, Timothy V.

    2013-02-15

    Current methods of estimating air emissions from research and development (R&D) activities use a wide range of release fractions or emission factors with bases ranging from empirical to semi-empirical. Although considered conservative, the uncertainties and confidence levels of the existing methods have not been reported. Chemical emissions were estimated from sampling data taken from four research facilities over ten years. The approach was to use a Monte Carlo technique to create distributions of annual emission estimates for target compounds detected in source test samples. Distributions were created for each year and building sampled for compounds with sufficient detection frequency to qualify for the analysis. The results using the Monte Carlo technique without applying a filter to remove negative emission values showed almost all distributions spanning zero, and forty percent of the distributions having a negative mean. This indicates that emissions are so low as to be indistinguishable from building background. Application of a filter to allow only positive values in the distribution provided a more realistic value for emissions and increased the distribution mean by an average of sixteen percent. Release fractions were calculated by dividing the emission estimates by a building chemical inventory quantity. Two variations were used for this quantity: chemical usage, and chemical usage plus one-half standing inventory. Filters were applied so that only release fraction values from zero to one were included in the resulting distributions. Release fractions had a wide range among chemicals and among data sets for different buildings and/or years for a given chemical. Regressions of release fractions to molecular weight and vapor pressure showed weak correlations. Similarly, regressions of mean emissions to chemical usage, chemical inventory, molecular weight and vapor pressure also gave weak correlations. These results highlight the difficulties in estimating

  1. Differences in the action of lower and higher chlorinated polychlorinated naphthalene (PCN) congeners on estrogen dependent breast cancer cell line viability and apoptosis, and its correlation with Ahr and CYP1A1 expression.

    PubMed

    Gregoraszczuk, Ewa L; Barć, Justyna; Falandysz, Jerzy

    2016-07-29

    There are data showing that exposition to PCNs mixture increased incidence of gastrointestinal and respiratory neoplasms, but data regarding incidence of hormone-dependent cancer so far not shown. The objective was to determine if exposure to single lower and higher chlorinated PCN congeners is associated with altered proliferation and apoptosis of estrogen dependent breast cancer cells, and whether such effects are related to induction of AhR and CYP1A1 protein expression. MCF-7 cells were exposed to PCN 34, 39, 42, 46, 48, 52, 53, 54, 66, 67, 70, 71, 73 and 74 at concentrations of 100-10,000pg/ml. We evaluated the action of these PCN congeners on cell proliferation, DNA fragmentation and caspase-8,-9 activity. AhR and CYP1A1 protein expression and CYP1A1 activity was evaluated at a concentration of 1000pg/ml. An opposite action of tri- to tetraCNs than of penta-to heptaCNs on cell proliferation and apoptosis was evident. Tetra PCNs increased cell proliferation, but had no effect on DNA fragmentation nor caspase activity. Fast induction of CYP1A1 protein expression under the influence of lower chlorinated PCNs suggests faster metabolism and a possible stimulatory action of locally formed metabolites on cell proliferation. None of the higher chlorinated PCNs affected cell proliferation but all higher chlorinated PCNs increased caspase-8 activity, and hexa PCNs also increased caspase-9 activity. The rapid activation of the Ah receptor and CYP1A1 protein expression by higher chlorinated PCNs point to their toxicity; however, it is not sufficient for potential carcinogenicity. Action of lower chlorinated naphthalenes metabolites should be explored.

  2. Modeling Chemical Detection Sensitivities of Active and Passive Remote Sensing Systems

    SciTech Connect

    Scharlemann, E T

    2003-07-28

    During nearly a decade of remote sensing programs under the auspices of the U. S. Department of Energy (DOE), LLNL has developed a set of performance modeling codes--called APRS--for both Active and Passive Remote Sensing systems. These codes emphasize chemical detection sensitivity in the form of minimum detectable quantities with and without background spectral clutter and in the possible presence of other interfering chemicals. The codes have been benchmarked against data acquired in both active and passive remote sensing programs at LLNL and Los Alamos National Laboratory (LANL). The codes include, as an integral part of the performance modeling, many of the data analysis techniques developed in the DOE's active and passive remote sensing programs (e.g., ''band normalization'' for an active system, principal component analysis for a passive system).

  3. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    Although these studies indicate that wastewater-treatment plant effluent is a conduit for endocrine active chemicals to surface waters, endocrine active chemicals also were present in surface waters with no obvious wastewater-treatment plant effluent sources. Endocrine active chemicals were detected and indicators of endocrine disruption in fish were measured at numerous sites upstream from discharge of wastewater-treatment plant effluent. These observations indicate that other unidentified sources of endocrine active chemicals exist, such as runoff from land surfaces, atmospheric deposition, inputs from onsite septic systems, or other groundwater sources. Alternatively, some endocrine active chemicals may not yet have been identified or measured. The presence of biological indicators of endocrine disruption in male fish indicates that the fish are exposed to endocrine active chemicals. However indicators of endocrine disruption in male fish does not indicate an effect on fish reproduction or changes in fish populations.

  4. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1990-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  5. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, H.K.; Wamser, C.C.

    1990-04-17

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membranes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanine derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  6. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers

    DOEpatents

    Lonsdale, Harold K.; Wamser, Carl C.

    1988-01-01

    The preparation of a novel class of thin film membranes by interfacial polymerization is disclosed, said membanes incorporating as part of their polymeric structure the functionality of monomeric or oligomeric precursors. Specific embodiments include porphyrin and phthalocyanime derivatives that are photochemically or electrochemically active, as well as chemically asymmetric membranes.

  7. Application of Protein Expression Profiling to Screen Chemicals for Androgenic Activity.

    EPA Science Inventory

    Protein expression changes can be used for detection of biomarkers that can be applied diagnostically to screen chemicals for endocrine modifying activity. In this study, Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) coupled with a s...

  8. Chemical composition and biological activity of the essential oil of rhizome of Zingiber zerumbet (L.) smith

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Technical Abstract: The aim was designed to study the biological activity and chemical composition of essential oil of Zingiber zerumbet (L.) Smith. The essential oil extracted from the rhizome of the plant was analysed by gas chromatography-mass spectroscopy and its major components amounting t...

  9. Phoenix dactylifera L. spathe essential oil: Chemical composition and repellent activity against the yellow fever mosquito

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Date palm, Phoenix dactylifera L. (Arecaceae), grows commonly in the Arabian Peninsula and is traditionally used to treat various diseases. The aim of the present study was to identify chemical composition of the essential oil and to investigate the repellent activity. The essential oil of P. dacty...

  10. Lantana montevidensis Essential Oil: Chemical Composition and Mosquito Repellent Activity against Aedes aegypti

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The essential oil (EO) of Lantana montevidensis (Spreng.) Briq. (L. sellowiana Link & Otto) was investigated for its chemical composition and mosquito repellent activity. The essential oil obtained by hydrodistillation of aerial plant parts was analyzed by GC-FID and GC-MS. The major constituents we...

  11. Fenton-Driven Chemical Regeneration of MTBE-Spent Granular Activated Carbon -- A Pilot Study

    EPA Science Inventory

    MTBE-spent granular activated carbon (GAC) underwent 3 adsorption/oxidation cycles. Pilot-scale columns were intermittently placed on-line at a ground water pump and treat facility, saturated with MTBE, and regenerated with H2O2 under different chemical, physical, and operational...

  12. Kinetic effect of Pd additions on the hydrogen uptake of chemically activated, ultramicroporous carbon

    SciTech Connect

    Bhat, Vinay V; Contescu, Cristian I; Gallego, Nidia C

    2010-01-01

    The effect of mixing chemically-activated ultramicroporous carbon (UMC) with Pd nanopowder is investigated. Results show that Pd addition doubles the rate of hydrogen uptake, but does not enhance the hydrogen capacity or improve desorption kinetics. The effect of Pd on the rate of hydrogen adsorption supports the occurrence of the hydrogen spillover mechanism in the Pd - UMC system.

  13. Evaluation of surface waters associated with animal feeding operations for estrogenic chemicals and activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogens and estrogenic activity (EA) were evaluated in surface waters associated with animal feeding operations. Water was sampled at 19 sites in 12 states using discrete (n=41) and POCIS (n=19) sampling methods. Estrogenic chemicals measured in unfiltered water by GC/MS2 included: estrone (E1),17...

  14. Combining phosphate and bacteria removal on chemically active filter membranes allows prolonged storage of drinking water.

    PubMed

    Rotzetter, A C C; Kellenberger, C R; Schumacher, C M; Mora, C; Grass, R N; Loepfe, M; Luechinger, N A; Stark, W J

    2013-11-13

    A chemically active filtration membrane with incorporated lanthanum oxide nanoparticles enables the removal of bacteria and phosphate at the same time and thus provides a simple device for preparation of drinking water and subsequent safe storage without using any kind of disinfectants.

  15. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

  16. Chemical Genetics: receptor-ligand pairs for rapid manipulation of neuronal activity

    PubMed Central

    Wulff, Peer; Arenkiel, Benjamin R.

    2012-01-01

    Towards the functional dissection of neuronal circuits, a number of new genetic tools have been developed that enable rapid and reversible manipulation of genetically defined neuronal subtypes in intact mammalian brain circuits. Alongside the breakthrough technology of optogenetics, receptor-ligand pairs provide complementary approaches to modulate neuronal activity using chemical-genetics. PMID:22119143

  17. OVEREXPRESSION OF ANTIOXIDANT ENZYMES UPREGULATES ARYL HYDROCARBON RECEPTOR EXPRESSION VIA INCREASED SP1 DNA-BINDING ACTIVITY

    PubMed Central

    Tang, Tian; Lin, Xinghua; Yang, Hong; Zhou, LiChun; Wang, Zefen; Shan, Guang; Guo, ZhongMao

    2010-01-01

    We previously reported up-regulation of aryl hydrocarbon receptor (AhR) expression as a mechanism by which overexpression of Cu/Zn-superoxide dismutase (SOD) and/or catalase accelerates benzo(a)pyrene (BaP) detoxification in mouse aorta endothelial cells (MAECs). The objective of this study was to investigate the regulatory role of specificity protein-1 (Sp1) in AhR expression in MAECs that overexpress Cu/Zn-SOD and/or catalase. Our data demonstrated comparable levels of nuclear Sp1 protein in the transgenic and wild-type MAECs; however, binding of Sp1 protein to the AhR promoter region was more than 2-fold higher in MAECs overexpressing Cu/Zn-SOD and/or catalase than in wild-type cells. Inhibition of Sp1 binding to the AhR promoter by mithramycin A reduced AhR expression and eliminated the differences between wild-type MAECs, and three lines of transgenic cells. Functional promoter analysis indicated that AhR promoter activity was significantly higher in MAECs overexpressing catalase than in wild-type cells. Mutation of an AhR promoter Sp1-binding site or addition of hydrogen peroxide to the culture medium reduced AhR promoter activity, and decreased the differences between wild-type MAECs and transgenic cells overexpressing catalase. These results suggest that increased Sp1 binding to the AhR promoter region is an underlying mechanism for up-regulation of AhR expression in MAECs that overexpress Cu/Zn-SOD and/or catalase. PMID:20478378

  18. Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver

    SciTech Connect

    Qu Xiaoyu; Metz, Richard P.; Porter, Weston W.; Cassone, Vincent M.; Earnest, David J.

    2009-02-01

    The aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) are transcription factors that express Per-Arnt-Sim (PAS) DNA-binding motifs and mediate the metabolism of drugs and environmental toxins in the liver. Because these transcription factors interact with other PAS genes in molecular feedback loops forming the mammalian circadian clockworks, we determined whether targeted disruption or siRNA inhibition of Per1 and Per2 expression alters toxin-mediated regulation of the AhR signaling pathway in the mouse liver and Hepa1c1c7 hepatoma cells in vitro. Treatment with the prototypical Ahr ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), had inductive effects on the primary targets of AhR signaling, Cyp1A1 and Cyp1B1, in the liver of all animals, but genotype-based differences were evident such that the toxin-mediated induction of Cyp1A1 expression was significantly greater (2-fold) in mice with targeted disruption of Per1 (Per1{sup ldc} and Per1{sup ldc}/Per2{sup ldc}). In vitro experiments yielded similar results demonstrating that siRNA inhibition of Per1 significantly increases the TCDD-induced expression of Cyp1A1 and Cyp1B1 in Hepa1c1c7 cells. Per2 inhibition in siRNA-infected Hepa1c1c7 cells had the opposite effect and significantly decreased both the induction of these p450 genes as well as AhR and Arnt expression in response to TCDD treatment. These findings suggest that Per1 may play a distinctive role in modulating AhR-regulated responses to TCDD in the liver.

  19. Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

    PubMed

    Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

    2016-09-01

    4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine.

  20. Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor

    PubMed Central

    Kaye, Joel; Piryatinsky, Victor; Birnberg, Tal; Hingaly, Tal; Raymond, Emanuel; Kashi, Rina; Amit-Romach, Einat; Caballero, Ignacio S.; Towfic, Fadi; Ator, Mark A.; Rubinstein, Efrat; Laifenfeld, Daphna; Orbach, Aric; Shinar, Doron; Marantz, Yael; Grossman, Iris; Knappertz, Volker; Hayden, Michael R.; Laufer, Ralph

    2016-01-01

    Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington’s disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod-treated mice. The AhR pathway modulates the differentiation and function of several cell populations, many of which play an important role in neuroinflammation. We therefore tested the consequences of AhR activation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) using AhR knockout mice. We demonstrate that the pronounced effect of laquinimod on clinical score, CNS inflammation, and demyelination in EAE was abolished in AhR−/− mice. Furthermore, using bone marrow chimeras we show that deletion of AhR in the immune system fully abrogates, whereas deletion within the CNS partially abrogates the effect of laquinimod in EAE. These data strongly support the idea that AhR is necessary for the efficacy of laquinimod in EAE and that laquinimod may represent a first-in-class drug targeting AhR for the treatment of multiple sclerosis and other neurodegenerative diseases. PMID:27671624

  1. Physical and chemical properties and adsorption type of activated carbon prepared from plum kernels by NaOH activation.

    PubMed

    Tseng, Ru-Ling

    2007-08-25

    Activated carbon was prepared from plum kernels by NaOH activation at six different NaOH/char ratios. The physical properties including the BET surface area, the total pore volume, the micropore ratio, the pore diameter, the burn-off, and the scanning electron microscope (SEM) observation as well as the chemical properties, namely elemental analysis and temperature programmed desorption (TPD), were measured. The results revealed a two-stage activation process: stage 1 activated carbons were obtained at NaOH/char ratios of 0-1, surface pyrolysis being the main reaction; stage 2 activated carbons were obtained at NaOH/char ratios of 2-4, etching and swelling being the main reactions. The physical properties of stage 2 activated carbons were similar, and specific area was from 1478 to 1887m(2)g(-1). The results of reaction mechanism of NaOH activation revealed that it was apparently because of the loss ratio of elements C, H, and O in the activated carbon, and the variations in the surface functional groups and the physical properties. The adsorption of the above activated carbons on phenol and three kinds of dyes (MB, BB1, and AB74) were used for an isotherm equilibrium adsorption study. The data fitted the Langmuir isotherm equation. Various kinds of adsorbents showed different adsorption types; separation factor (R(L)) was used to determine the level of favorability of the adsorption type. In this work, activated carbons prepared by NaOH activation were evaluated in terms of their physical properties, chemical properties, and adsorption type; and activated carbon PKN2 was found to have most application potential.

  2. Force-activated reactivity switch in a bimolecular chemical reaction at the single molecule level

    NASA Astrophysics Data System (ADS)

    Szoszkiewicz, Robert; Garcia-Manyes, Sergi; Liang, Jian; Kuo, Tzu-Ling; Fernandez, Julio M.

    2009-10-01

    Mechanical force is a distinct and usually less explored way to activate chemical reaction because it can deform the reacting molecules along a well-defined direction of the reaction coordinate. However, the effect of mechanical force on the free- energy surface that governs a chemical reaction is still largely unknown. The combination of protein engineering with single-molecule force-clamp spectroscopy allows us to study the influence of mechanical force on the rate at which a protein disulfide bond is reduced by some reducing agents in a bimolecular substitution reaction (so-called SN2). We found that cleavage of a protein disulfide bond by hydroxide anions exhibits an abrupt reactivity ``switch'' at 500 pN, after which the accelerating effect of force on the rate of an SN2 chemical reaction greatly diminishes. We propose that an abrupt force- induced conformational change of the protein disulfide bond shifts its ground state, drastically changing its reactivity in SN2 chemical reactions. Our experiments directly demonstrate the action of a force-activated switch in the chemical reactivity of a single molecule. References: S. Garcia-Manyes, J. Liang, R. Szoszkiewicz, T-L. Kuo and J. M. Fernandez, Nature Chemistry, 1, 236-242, 2009.

  3. Active chlorine and nitric oxide formation from chemical rocket plume afterburning

    NASA Technical Reports Server (NTRS)

    Leone, D. M.; Turns, S. R.

    1994-01-01

    Chlorine and oxides of nitrogen (NO(x)) released into the atmosphere contribute to acid rain (ground level or low-altitude sources) and ozone depletion from the stratosphere (high-altitude sources). Rocket engines have the potential for forming or activating these pollutants in the rocket plume. For instance, H2/O2 rockets can produce thermal NO(x) in their plumes. Emphasis, in the past, has been placed on determining the impact of chlorine release on the stratosphere. To date, very little, if any, information is available to understand what contribution NO(x) emissions from ground-based engine testing and actual rocket launches have on the atmosphere. The goal of this work is to estimate the afterburning emissions from chemical rocket plumes and determine their local stratospheric impact. Our study focuses on the space shuttle rocket motors, which include both the solid rocket boosters (SRB's) and the liquid propellant main engines (SSME's). Rocket plume afterburning is modeled employing a one-dimensional model incorporating two chemical kinetic systems: chemical and thermal equilibria with overlayed nitric oxide chemical kinetics (semi equilibrium) and full finite-rate chemical kinetics. Additionally, the local atmospheric impact immediately following a launch is modeled as the emissions diffuse and chemically react in the stratosphere.

  4. Comparison on pore development of activated carbon produced by chemical and physical activation from palm empty fruit bunch

    NASA Astrophysics Data System (ADS)

    Hidayat, A.; Sutrisno, B.

    2016-11-01

    It is well-known that activated carbon is considered to be the general adsorbent due to the large range of applications. Numerous works are being continuously published concerning its use as adsorbent for: treatment of potable water; purification of air; retention of toxins by respirators; removal of organic and inorganic pollutants from flue gases and industrial waste gases and water; recuperation of solvents and hydrocarbons volatilized from petroleum derivatives; catalysis; separation of gas mixtures (molecularsieve activated carbons); storage of natural gas and hydrogen; energy storage in supercapacitors; recovery of gold, silver and othernoble metals; etc. This work presents producing activated carbons from palm empty fruit bunch using both physical activation with CO2 and chemical activation with KOH. The resultant activated carbons were characterized by measuring their porosities and pore size distributions. A comparison of the textural characteristics and surface chemistry of the activated carbon from palm empty fruit bunch by the CO2 and the KOH activation leads to the following findings: An activated carbon by the CO2 activation under the optimum conditions has a BET surface area of 717 m2/g, while that by the KOH activation has a BET surface area of 613 m2/g. The CO2 activation generated a highly microporous carbon (92%) with a Type-I isotherm, while the KOH activation generated a mesoporous one (70%) with a type-IV isotherm, the pore volumes are 0.2135 and 0.7426 cm3.g-1 respectively. The average pore size of the activated carbons is 2.72 and 2.56 nm for KOH activation and CO2 activation, respectively. The FT-IR spectra indicated significant variation in the surface functional groups are quite different for the KOH activated and CO2 activated carbons.

  5. GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

    EPA Science Inventory

    Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

  6. Adaptive stress response pathways induced by environmental mixtures of bioaccumulative chemicals in dugongs.

    PubMed

    Jin, Ling; Gaus, Caroline; Escher, Beate I

    2015-06-02

    To address the poorly understood mixture effects of chemicals in the marine mammal dugong, we coupled equilibrium-based passive sampling in blubber to a range of in vitro bioassays for screening mixtures of bioaccumulative chemicals. The modes of action included early effect indicators along important toxicity pathways, such as induction of xenobiotic metabolism, and some integrative indicators downstream of the molecular initiating event, such as adaptive stress responses. Activation of aryl hydrocarbon receptor (AhR) and Nrf2-mediated oxidative stress response were found to be the most prominent effects, while the p53-mediated DNA damage response and NF-κB-mediated response to inflammation were not significantly affected. Although polychlorinated dibenzo-p-dioxins (PCDDs) quantified in the samples accounted for the majority of AhR-mediated activity, PCDDs explained less than 5% of the total oxidative stress response, despite their known ability to activate this pathway. Altered oxidative stress response was observed with both individual chemicals and blubber extracts subject to metabolic activation by rat liver S9 fraction. Metabolic activation resulted in both enhanced and reduced toxicity, suggesting the relevance and utility of incorporating metabolic enzymes into in vitro bioassays. Our approach provides a first insight into the burden of toxicologically relevant bioaccumulative chemical mixtures in dugongs and can be applied to lipid tissue of other wildlife species.

  7. Robust root growth in altered hydrotropic response1 (ahr1) mutant of Arabidopsis is maintained by high rate of cell production at low water potential gradient.

    PubMed

    Salazar-Blas, Amed; Noriega-Calixto, Laura; Campos, María E; Eapen, Delfeena; Cruz-Vázquez, Tania; Castillo-Olamendi, Luis; Sepulveda-Jiménez, Gabriela; Porta, Helena; Dubrovsky, Joseph G; Cassab, Gladys I

    2017-01-01

    Hydrotropism is the directional root growth response determined by water stimulus. In a water potential gradient system (WPGS) the roots of the Arabidopsis wild type have a diminished root growth compared to normal medium (NM). In contrast, the altered hydrotropic response1 (ahr1) mutant roots maintain their robust growth in the same WPGS. The aims of this work were to ascertain how ahr1 roots could sustain growth in the WPGS, with a special focus on the integration of cellular processes involved in the signaling that determines root growth during abiotic stress and their relation to hydrotropism. Cellular analysis of the root apical meristem of ahr1 mutant contrary to the wild type showed an absence of changes in the meristem length, the elongation zone length, the length of fully elongated cells, and the cell cycle duration. The robust and steady root growth of ahr1 seedlings in the WPGS is explained by the mutant capacity to maintain cell production and cell elongation at the same level as in the NM. Analysis of auxin response at a transcriptional level showed that roots of the ahr1 mutant had a lower auxin response when grown in the WPGS, compared to wild type, indicating that auxin signaling participates in attenuation of root growth under water stress conditions. Also, wild type plants exhibited a high increase in proline content while ahr1 mutants showed minimum changes in the Normal Medium→Water Stress Medium (NM→WSM), a lower water potential gradient system than the WPGS. Accordingly, in this condition, gene expression of Δ1-6 Pyrroline-5-Carboxylate Synthetase1 (P5CS1) involved in proline synthesis strongly increased in wild type but not in ahr1 seedlings. The ahr1 phenotype shows unique features since the mutant root cells continue to proliferate and grow in the presence of a progressively negative water potential gradient at a level comparable to wild type growing in the NM. As such, it represents an exceptional resource for understanding

  8. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  9. Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia

    PubMed Central

    Elnakady, Yasser A.; Rushdi, Ahmed I.; Franke, Raimo; Abutaha, Nael; Ebaid, Hossam; Baabbad, Mohannad; Omar, Mohamed O. M.; Al Ghamdi, Ahmad A.

    2017-01-01

    Propolis has been used to treat several diseases since ancient times, and is an important source of bioactive natural compounds and drug derivatives. These properties have kept the interest of investigators around the world, leading to the investigation of the chemical and biological properties and application of propolis. In this report, the chemical constituents that are responsible for the anticancer activities of propolis were analyzed. The propolis was sourced from Al-Baha in the southern part of the Kingdom of Saudi Arabia. Standard protocols for chemical fractionation and bioactivity-guided chemical analysis were used to identify the bio-active ethyl acetate fraction. The extraction was performed in methanol and then analyzed by gas chromatography-mass spectrometry (GC-MS). The major compounds are triterpenoids, with a relative concentration of 74.0%; steroids, with a relative concentration of 9.8%; and diterpenoids, with a relative concentration of 7.9%. The biological activity was characterized using different approaches and cell-based assays. Propolis was found to inhibit the proliferation of cancer cells in a concentration-dependent manner through apoptosis. Immunofluorescence staining with anti-α-tubulin antibodies and cell cycle analysis indicated that tubulin and/or microtubules are the cellular targets of the L-acetate fraction. This study demonstrates the importance of Saudi propolis as anti-cancer drug candidates. PMID:28165013

  10. Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Elnakady, Yasser A.; Rushdi, Ahmed I.; Franke, Raimo; Abutaha, Nael; Ebaid, Hossam; Baabbad, Mohannad; Omar, Mohamed O. M.; Al Ghamdi, Ahmad A.

    2017-02-01

    Propolis has been used to treat several diseases since ancient times, and is an important source of bioactive natural compounds and drug derivatives. These properties have kept the interest of investigators around the world, leading to the investigation of the chemical and biological properties and application of propolis. In this report, the chemical constituents that are responsible for the anticancer activities of propolis were analyzed. The propolis was sourced from Al-Baha in the southern part of the Kingdom of Saudi Arabia. Standard protocols for chemical fractionation and bioactivity-guided chemical analysis were used to identify the bio-active ethyl acetate fraction. The extraction was performed in methanol and then analyzed by gas chromatography-mass spectrometry (GC-MS). The major compounds are triterpenoids, with a relative concentration of 74.0%; steroids, with a relative concentration of 9.8%; and diterpenoids, with a relative concentration of 7.9%. The biological activity was characterized using different approaches and cell-based assays. Propolis was found to inhibit the proliferation of cancer cells in a concentration-dependent manner through apoptosis. Immunofluorescence staining with anti-α-tubulin antibodies and cell cycle analysis indicated that tubulin and/or microtubules are the cellular targets of the L-acetate fraction. This study demonstrates the importance of Saudi propolis as anti-cancer drug candidates.

  11. Eucalyptus (gracilis, oleosa, salubris, and salmonophloia) essential oils: their chemical composition and antioxidant and antimicrobial activities.

    PubMed

    Ben Marzoug, Hajer Naceur; Bouajila, Jalloul; Ennajar, Monia; Lebrihi, Ahmed; Mathieu, Florence; Couderc, François; Abderraba, Manef; Romdhane, Mehrez

    2010-08-01

    Essential oils of four different Eucalyptus species (Eucalyptus salubris, Eucalyptus salmonophloia, Eucalyptus oleosa, and Eucalyptus gracilis) grown in southern Tunisia were screened for their antioxidant and antimicrobial properties as well as their chemical compositions. According to gas chromatography-flame ionization detection and gas chromatography-mass spectrometry analysis, chemical compositions of the Eucalyptus species E. salubris (27 compounds; 99.2%), E. salmonophloia (31 compounds; 99.2%), E. oleosa (32 compounds; 97.6%), and E. gracilis (18 compounds; 97.7%) were identified. In the 1,1-diphenyl-2-picrylhydrazyl assay, the antioxidant activity was in the range of 12.0-52.8 mg/mL, whereas in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate assay, E. oleosa (176.5 +/- 3.1 mg/L) gave the best inhibition result. To evaluate antimicrobial activity, all essential oils were tested against bacteria (two Gram-positive and two Gram-negative), two yeast, and two fungi. Essential oils exhibited an interesting antibacterial activity against all microorganisms tested (activity was better against Gram-positive bacteria) except for Staphylococcus aureus and Escherichia coli. Correlations between chemical composition and biological and antioxidant activities were studied.

  12. Enhanced catalytic activity in strained chemically exfoliated WS₂ nanosheets for hydrogen evolution.

    PubMed

    Voiry, Damien; Yamaguchi, Hisato; Li, Junwen; Silva, Rafael; Alves, Diego C B; Fujita, Takeshi; Chen, Mingwei; Asefa, Tewodros; Shenoy, Vivek B; Eda, Goki; Chhowalla, Manish

    2013-09-01

    Efficient evolution of hydrogen through electrocatalysis at low overpotentials holds tremendous promise for clean energy. Hydrogen evolution can be easily achieved by electrolysis at large potentials that can be lowered with expensive platinum-based catalysts. Replacement of Pt with inexpensive, earth-abundant electrocatalysts would be significantly beneficial for clean and efficient hydrogen evolution. To this end, promising results have been reported using 2H (trigonal prismatic) XS₂ (where X  =  Mo or W) nanoparticles with a high concentration of metallic edges. The key challenges for XS₂ are increasing the number and catalytic activity of active sites. Here we report monolayered nanosheets of chemically exfoliated WS₂ as efficient catalysts for hydrogen evolution with very low overpotentials. Analyses indicate that the enhanced electrocatalytic activity of WS₂ is associated with the high concentration of the strained metallic 1T (octahedral) phase in the as-exfoliated nanosheets. Our results suggest that chemically exfoliated WS₂ nanosheets are interesting catalysts for hydrogen evolution.

  13. Spatiotemporal regulation of chemical reaction kinetics of cell surface molecules by active remodeling of cortical actin

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Bhaswati; Chaudhuri, Abhishek; Gowrishankar, Kripa; Mayor, Satyajit; Rao, Madan

    2010-03-01

    Cell surface proteins such as lipid tethered GPI-anchored proteins and Ras-proteins are distributed as monomers and nanoclusters on the surface of living cells. Recent work from our laboratory suggests that the spatial distribution and dynamics of formation and breakup of these nanoclusters is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we propose a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. Here we study the consequences of such active actin based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that active remodeling of cortical actin, can give rise to a dramatic increase in the reaction efficiency and output levels. In general, such actin driven clustering of membrane proteins could be a cellular mechanism to spatiotemporally regulate and amplify local chemical reaction rates, in the context of signalling and endocytosis.

  14. Chemical composition and antibacterial activity of Opuntia ficus-indica f. inermis (cactus pear) flowers.

    PubMed

    Ennouri, Monia; Ammar, Imene; Khemakhem, Bassem; Attia, Hamadi

    2014-08-01

    Opuntia ficus-indica f. inermis (cactus pear) flowers have wide application in folk medicine. However, there are few reports focusing on their biological activity and were no reports on their chemical composition. The nutrient composition and hexane extracts of Opuntia flowers at 4 flowering stages and their antibacterial and antifungal activities were investigated. The chemical composition showed considerable amounts of fiber, protein, and minerals. Potassium (K) was the predominant mineral followed by calcium (Ca), magnesium (Mg), sodium (Na), iron (Fe), and zinc (Zn). The main compounds in the various hexane extracts were 9.12-octadecadienoic acid (29-44%) and hexadecanoic acid (8.6-32%). The antibacterial activity tests showed that O. inermis hexane extracts have high effectiveness against Escherichia coli and Staphylococcus aureus, making this botanical source a potential contender as a food preservative or food control additive.

  15. Chemical composition and larvicidal activity of several essential oils from Hypericum species from Tunisia.

    PubMed

    Rouis, Zyed; Laamari, Ali; Abid, Nabil; Elaissi, Ameur; Cioni, Pier Luigi; Flamini, Guido; Aouni, Mahjoub

    2013-02-01

    The chemical composition of the essential oils extracted from some Tunisian Hypericum species and their larvicidal activity against Culex pipiens larvae were evaluated. The chemical compositions of the essential oils from the aerial plant parts were analyzed using gas chromatography-mass spectrometry. One hundred and thirty-four compounds were identified, ranging between 85.1 and 95.4 % of the oil's composition. The components were monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, non-terpenic hydrocarbons, and others. The larvicidal activity of the essential oils was evaluated using a method recommended by WHO. Larvicidal tests revealed that essential oils from the Hypericum species have a significant larvicidal activity against C. pipiens, with LC(50) ranging between 102.82 and 194.70 ppm. The most powerful essential oils against these larvae were Hypericum tomentosum and Hypericum humifusum samples, followed by the essential oil of Hypericum perforatum.

  16. Seasonal Variation, Chemical Composition and Antioxidant activity of Brazilian Propolis Samples

    PubMed Central

    Teixeira, Érica Weinstein; Message, Dejair; Negri, Giuseppina; Stringheta, Paulo César

    2010-01-01

    Total phenolic contents, antioxidant activity and chemical composition of propolis samples from three localities of Minas Gerais state (southeast Brazil) were determined. Total phenolic contents were determined by the Folin–Ciocalteau method, antioxidant activity was evaluated by DPPH, using BHT as reference, and chemical composition was analyzed by GC/MS. Propolis from Itapecerica and Paula Cândido municipalities were found to have high phenolic contents and pronounced antioxidant activity. From these extracts, 40 substances were identified, among them were simple phenylpropanoids, prenylated phenylpropanoids, sesqui- and diterpenoids. Quantitatively, the main constituent of both samples was allyl-3-prenylcinnamic acid. A sample from Virginópolis municipality had no detectable phenolic substances and contained mainly triterpenoids, the main constituents being α- and β-amyrins. Methanolic extracts from Itapecerica and Paula Cândido exhibited pronounced scavenging activity towards DPPH, indistinguishable from BHT activity. However, extracts from Virginópolis sample exhibited no antioxidant activity. Total phenolic substances, GC/MS analyses and antioxidant activity of samples from Itapecerica collected monthly over a period of 1 year revealed considerable variation. No correlation was observed between antioxidant activity and either total phenolic contents or contents of artepillin C and other phenolic substances, as assayed by CG/MS analysis. PMID:18955317

  17. Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples.

    PubMed

    Teixeira, Erica Weinstein; Message, Dejair; Negri, Giuseppina; Salatino, Antonio; Stringheta, Paulo César

    2010-09-01

    Total phenolic contents, antioxidant activity and chemical composition of propolis samples from three localities of Minas Gerais state (southeast Brazil) were determined. Total phenolic contents were determined by the Folin-Ciocalteau method, antioxidant activity was evaluated by DPPH, using BHT as reference, and chemical composition was analyzed by GC/MS. Propolis from Itapecerica and Paula Cândido municipalities were found to have high phenolic contents and pronounced antioxidant activity. From these extracts, 40 substances were identified, among them were simple phenylpropanoids, prenylated phenylpropanoids, sesqui- and diterpenoids. Quantitatively, the main constituent of both samples was allyl-3-prenylcinnamic acid. A sample from Virginópolis municipality had no detectable phenolic substances and contained mainly triterpenoids, the main constituents being α- and β-amyrins. Methanolic extracts from Itapecerica and Paula Cândido exhibited pronounced scavenging activity towards DPPH, indistinguishable from BHT activity. However, extracts from Virginópolis sample exhibited no antioxidant activity. Total phenolic substances, GC/MS analyses and antioxidant activity of samples from Itapecerica collected monthly over a period of 1 year revealed considerable variation. No correlation was observed between antioxidant activity and either total phenolic contents or contents of artepillin C and other phenolic substances, as assayed by CG/MS analysis.

  18. Evaluation of mycobactericidal activity of selected chemical disinfectants and antiseptics according to European standards

    PubMed Central

    Bocian, Ewa; Grzybowska, Wanda; Tyski, Stefan

    2014-01-01

    Background The history of the investigation of standardized mycobactericidal activity of disinfectants and antiseptics is not very long. There is growing interest among the manufacturers of disinfectants in carrying out research on the antimicrobial activities in accordance with European standards (EN). This research could facilitate the introduction of high-quality disinfectants to the market. The aim of this study was to evaluate the mycobactericidal activity of selected chemical disinfectants and antiseptics used in the medical and veterinary fields. Material/Methods This study included 19 products submitted to the National Medicines Institute in Poland for evaluation of mycobactericidal activity. These products contain in their composition active substances belonging to different chemical groups, including aldehydes, alcohols, amines, quaternary ammonium compounds, phenols, guanidine, and oxidizing compounds. This study, conducted according to the manufacturers’ description of the preparations, was carried out in accordance with European standards, which also met the Polish standards: PN-EN 14204: 2013, PN-EN 14348: 2006, and PN-EN 14563: 2012. Results Tested products for disinfection and antiseptics containing active substances from different chemical groups showed high mycobactericidal activity and met the requirements of the appropriate European standards in most cases. In the case of products containing guanidine and amine compounds, the concentration of active ingredients used in the test and the test conditions specified by the manufacturer did not provide the mycobactericidal activity required by the standards. Conclusions Prior to the launch of a new product on the market, it is important to establish the appropriate usage and testing conditions of the preparation, such as its practical concentration, contact time, and environment condition (clean or dirty). PMID:24755666

  19. Influence of Copper Nanoparticles on the Physical-Chemical Properties of Activated Sludge

    PubMed Central

    Chen, Hong; Zheng, Xiong; Chen, Yinguang; Li, Mu; Liu, Kun; Li, Xiang

    2014-01-01

    The physical-chemical properties of activated sludge, such as flocculating ability, hydrophobicity, surface charge, settleability, dewaterability and bacteria extracellular polymer substances (EPS), play vital roles in the normal operation of wastewater treatment plants (WWTPs). The nanoparticles released from commercial products will enter WWTPs and can induce potential adverse effects on activated sludge. This paper focused on the effects of copper nanoparticles (CuNPs) on these specific physical-chemical properties of activated sludge. It was found that most of these properties were unaffected by the exposure to lower CuNPs concentration (5 ppm), but different observation were made at higher CuNPs concentrations (30 and 50 ppm). At the higher CuNPs concentrations, the sludge surface charge increased and the hydrophobicity decreased, which were attributed to more Cu2+ ions released from the CuNPs. The carbohydrate content of EPS was enhanced to defense the toxicity of CuNPs. The flocculating ability was found to be deteriorated due to the increased cell surface charge, the decreased hydrophobicity, and the damaged cell membrane. The worsened flocculating ability made the sludge flocs more dispersed, which further increased the toxicity of the CuNPs by increasing the availability of the CuNPs to the bacteria present in the sludge. Further investigation indicated that the phosphorus removal efficiency decreased at higher CuNPs concentrations, which was consistent with the deteriorated physical-chemical properties of activated sludge. It seems that the physical-chemical properties can be used as an indicator for determining CuNPs toxicity to the bacteria in activated sludge. This work is important because bacteria toxicity effects to the activated sludge caused by nanoparticles may lead to the deteriorated treatment efficiency of wastewater treatment, and it is therefore necessary to find an easy way to indicate this toxicity. PMID:24663333

  20. Influence of copper nanoparticles on the physical-chemical properties of activated sludge.

    PubMed

    Chen, Hong; Zheng, Xiong; Chen, Yinguang; Li, Mu; Liu, Kun; Li, Xiang

    2014-01-01

    The physical-chemical properties of activated sludge, such as flocculating ability, hydrophobicity, surface charge, settleability, dewaterability and bacteria extracellular polymer substances (EPS), play vital roles in the normal operation of wastewater treatment plants (WWTPs). The nanoparticles released from commercial products will enter WWTPs and can induce potential adverse effects on activated sludge. This paper focused on the effects of copper nanoparticles (CuNPs) on these specific physical-chemical properties of activated sludge. It was found that most of these properties were unaffected by the exposure to lower CuNPs concentration (5 ppm), but different observation were made at higher CuNPs concentrations (30 and 50 ppm). At the higher CuNPs concentrations, the sludge surface charge increased and the hydrophobicity decreased, which were attributed to more Cu2+ ions released from the CuNPs. The carbohydrate content of EPS was enhanced to defense the toxicity of CuNPs. The flocculating ability was found to be deteriorated due to the increased cell surface charge, the decreased hydrophobicity, and the damaged cell membrane. The worsened flocculating ability made the sludge flocs more dispersed, which further increased the toxicity of the CuNPs by increasing the availability of the CuNPs to the bacteria present in the sludge. Further investigation indicated that the phosphorus removal efficiency decreased at higher CuNPs concentrations, which was consistent with the deteriorated physical-chemical properties of activated sludge. It seems that the physical-chemical properties can be used as an indicator for determining CuNPs toxicity to the bacteria in activated sludge. This work is important because bacteria toxicity effects to the activated sludge caused by nanoparticles may lead to the deteriorated treatment efficiency of wastewater treatment, and it is therefore necessary to find an easy way to indicate this toxicity.

  1. Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta).

    PubMed

    Mao, Wenjun; Li, Hongyan; Li, Yi; Zhang, Huijuan; Qi, Xiaohui; Sun, Haihong; Chen, Yin; Guo, Shoudong

    2009-01-01

    A polysaccharide was isolated from marine green algae Monostroma latissimum, and its chemical characteristic and anticoagulant activity were investigated. The results demonstrated that the polysaccharide was high rhamnose-containing sulfated polysaccharide, and was mainly composed of 1,2-linked l-rhamnose residues with sulfate groups substituted at positions C-3 and/or C-4. The sulfated polysaccharide exhibited high anticoagulant activities by assays of the activated partial thromboplastin time (APTT) and thrombin time (TT). The anticoagulant property of the sulfated polysaccharide was mainly attributed to powerful potentiation thrombin by heparin cofactor II.

  2. Estimating the toxicities of organic chemicals to bioluminescent bacteria and activated sludge.

    PubMed

    Ren, Shijin; Frymier, Paul D

    2002-10-01

    Toxicity assays based on bioluminescent bacteria have several advantages including a quick response and an easily measured signal. The Shk1 assay is a procedure for wastewater toxicity testing based on the bioluminescent bacterium Shk1. Using the Shk1 assay, the toxicity of 98 organic chemicals were measured and EC50 values were obtained. Quantitative structure-activity relationship (QSAR) models based on the logarithm of the octanol-water partition coefficient (log(Kow)) were developed for individual groups of organic chemicals with different functional groups. The correlation coefficients for different groups of organic compounds varied between 0.69 and 0.99. An overall QSAR model without discriminating the functional groups, which can be used for a quick estimate of the toxicities of organic chemicals, was also developed and model predictions were compared to experimental data. The model accuracy was found to be one order of magnitude from the observed values.

  3. Effect of mechanical activation on structure changes and reactivity in further chemical modification of lignin.

    PubMed

    Zhao, Xiaohong; Zhang, Yanjuan; Hu, Huayu; Huang, Zuqiang; Yang, Mei; Chen, Dong; Huang, Kai; Huang, Aimin; Qin, Xingzhen; Feng, Zhenfei

    2016-10-01

    Lignin was treated by mechanical activation (MA) in a customized stirring ball mill, and the structure and reactivity in further esterification were studied. The chemical structure and morphology of MA-treated lignin and the esterified products were analyzed by chemical analysis combined with UV/vis spectrometer, FTIR,NMR, SEM and particle size analyzer. The results showed that MA contributed to the increase of aliphatic hydroxyl, phenolic hydroxyl, carbonyl and carboxyl groups but the decrease of methoxyl groups. Moreover, MA led to the decrease of particle size and the increase of specific surface area and roughness of surface in lignin. The reactivity of lignin was enhanced significantly for the increase of hydroxyl content and the improvement of mass transfer in chemical reaction caused by the changes of molecular structure and morphological structure. The process of MA is green and simple, and is an effective method for enhancing the reactivity of lignin.

  4. Chemical composition measurements of the low activity waste (LAW) EPA-Series glasses

    SciTech Connect

    Fox, K.; Edwards, T. B.

    2016-03-01

    In this report, the Savannah River National Laboratory provides chemical analysis results for a series of simulated low activity waste glasses provided by Pacific Northwest National Laboratory as part of an ongoing development task. The measured chemical composition data are reported and compared with the targeted values for each component for each glass. A detailed review showed no indications of errors in the preparation or measurement of the study glasses. All of the measured sums of oxides for the study glasses fell within the interval of 100.2 to 100.8 wt %, indicating recovery of all components. Comparisons of the targeted and measured chemical compositions showed that the measured values for the glasses met the targeted concentrations within 10% for those components present at more than 5 wt %.

  5. Chemical analysis of Greek pollen - Antioxidant, antimicrobial and proteasome activation properties

    PubMed Central

    2011-01-01

    Background Pollen is a bee-product known for its medical properties from ancient times. In our days is increasingly used as health food supplement and especially as a tonic primarily with appeal to the elderly to ameliorate the effects of ageing. In order to evaluate the chemical composition and the biological activity of Greek pollen which has never been studied before, one sample with identified botanical origin from sixteen different common plant taxa of Greece has been evaluated. Results Three different extracts of the studied sample of Greek pollen, have been tested, in whether could induce proteasome activities in human fibroblasts. The water extract was found to induce a highly proteasome activity, showing interesting antioxidant properties. Due to this activity the aqueous extract was further subjected to chemical analysis and seven flavonoids have been isolated and identified by modern spectral means. From the methanolic extract, sugars, lipid acids, phenolic acids and their esters have been also identified, which mainly participate to the biosynthetic pathway of pollen phenolics. The total phenolics were estimated with the Folin-Ciocalteau reagent and the total antioxidant activity was determined by the DPPH method while the extracts and the isolated compounds were also tested for their antimicrobial activity by the dilution technique. Conclusions The Greek pollen is rich in flavonoids and phenolic acids which indicate the observed free radical scavenging activity, the effects of pollen on human fibroblasts and the interesting antimicrobial profile. PMID:21699688

  6. Chemical stability of a cold-active cellulase with high tolerance toward surfactants and chaotropic agent.

    PubMed

    Souza, Thaís V; Araujo, Juscemácia N; da Silva, Viviam M; Liberato, Marcelo V; Pimentel, Agnes C; Alvarez, Thabata M; Squina, Fabio M; Garcia, Wanius

    2016-03-01

    CelE1 is a cold-active endo-acting glucanase with high activity at a broad temperature range and under alkaline conditions. Here, we examined the effects of pH on the secondary and tertiary structures, net charge, and activity of CelE1. Although variation in pH showed a small effect in the enzyme structure, the activity was highly influenced at acidic conditions, while reached the optimum activity at pH 8. Furthermore, to estimate whether CelE1 could be used as detergent additives, CelE1 activity was evaluated in the presence of surfactants. Ionic and nonionic surfactants were not able to reduce CelE1 activity significantly. Therefore, CelE1 was found to be promising candidate for use as detergent additives. Finally, we reported a thermodynamic analysis based on the structural stability and the chemical unfolding/refolding process of CelE1. The results indicated that the chemical unfolding proceeds as a reversible two-state process. These data can be useful for biotechnological applications.

  7. Sequential extraction study of stability of adsorbed mercury in chemically modified activated carbons.

    PubMed

    Tong, Shitang; Fan, Mingxia; Mao, Lei; Jia, Charles Q

    2011-09-01

    Activated carbons chemically modified with sulfur and bromine are known for their greater effectiveness in capturing vapor Hg from coal combustion and other industrial flue gases. The stability of captured Hg in spent activated carbons determines the final fate of Hg and is critical to devising Hg control strategy. However, it remains a subject that is largely unknown, particularly for Br-treated activated carbons. Using a six-step sequential extraction procedure, this work evaluated the leaching potential of Hg captured with four activated carbons, one lignite-derived activated carbon, and three chemically treated with Br(2), KClO(3), and SO(2). The results demonstrated clearly the positive effect of Br- and SO(2)-treatment on the stability of captured Hg. The Hg captured with brominated activated carbon was very stable and likely in the form of mercurous bromide complex. Sulfur added at high temperature with SO(2) was able to stabilize a majority of Hg by forming sulfide and possibly sulfonate chelate. The presence of sulfate however made a small fraction of captured Hg (<10%) labile under mild conditions. Treating activated carbon with KClO(3) lowered the overall stability of captured Hg. A positive dependence of Hg stability on Hg loading temperature was observed for the first time.

  8. Chemical composition and lipoxygenase activity in soybeans (Glycine max L. Merr.) submitted to gamma irradiation

    NASA Astrophysics Data System (ADS)

    Barros, Érica Amanda de; Broetto, Fernando; Bressan, Dayanne F.; Sartori, Maria M. P.; Costa, Vladimir E.

    2014-05-01

    Soybeans are an important food due to their functional and nutritional characteristics. However, consumption by western populations is limited by the astringent taste of soybeans and their derivatives which results from the action of lipoxygenase, an enzyme activated during product processing. The aim of this study was to evaluate the effect of gamma irradiation on the chemical composition and specific activity of lipoxygenase in different soybean cultivars. Soybeans were stored in plastic bags and irradiated with doses of 2.5, 5 and 10 kGy. The chemical composition (moisture, protein, lipids, ashes, crude fiber, and carbohydrates) and lipoxygenase specific activity were determined for each sample. Gamma irradiation induced a small increase of protein and lipid content in some soybean cultivars, which did not exceed the highest content of 5% and 26%, respectively, when compared to control. Lipoxygenase specific activity decreased in the three cultivars with increasing gamma irradiation dose. In conclusion, the gamma irradiation doses used are suitable to inactivate part of lipoxygenase while not causing expressive changes in the chemical composition of the cultivars studied.

  9. Chemical Structure-Biological Activity Models for Pharmacophores’ 3D-Interactions

    PubMed Central

    Putz, Mihai V.; Duda-Seiman, Corina; Duda-Seiman, Daniel; Putz, Ana-Maria; Alexandrescu, Iulia; Mernea, Maria; Avram, Speranta

    2016-01-01

    Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners’ (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions. PMID:27399692

  10. Quantitative structure-activity relationship models of chemical transformations from matched pairs analyses.

    PubMed

    Beck, Jeremy M; Springer, Clayton

    2014-04-28

    The concepts of activity cliffs and matched molecular pairs (MMP) are recent paradigms for analysis of data sets to identify structural changes that may be used to modify the potency of lead molecules in drug discovery projects. Analysis of MMPs was recently demonstrated as a feasible technique for quantitative structure-activity relationship (QSAR) modeling of prospective compounds. Although within a small data set, the lack of matched pairs, and the lack of knowledge about specific chemical transformations limit prospective applications. Here we present an alternative technique that determines pairwise descriptors for each matched pair and then uses a QSAR model to estimate the activity change associated with a chemical transformation. The descriptors effectively group similar transformations and incorporate information about the transformation and its local environment. Use of a transformation QSAR model allows one to estimate the activity change for novel transformations and therefore returns predictions for a larger fraction of test set compounds. Application of the proposed methodology to four public data sets results in increased model performance over a benchmark random forest and direct application of chemical transformations using QSAR-by-matched molecular pairs analysis (QSAR-by-MMPA).

  11. Chemical Structure-Biological Activity Models for Pharmacophores' 3D-Interactions.

    PubMed

    Putz, Mihai V; Duda-Seiman, Corina; Duda-Seiman, Daniel; Putz, Ana-Maria; Alexandrescu, Iulia; Mernea, Maria; Avram, Speranta

    2016-07-08

    Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners' (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions.

  12. Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

    PubMed

    Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

    2016-09-01

    The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

  13. Metabolomic Assessment of Induced and Activated Chemical Defence in the Invasive Red Alga Gracilaria vermiculophylla

    PubMed Central

    Nylund, Göran M.; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  14. Metabolomic assessment of induced and activated chemical defence in the invasive red alga Gracilaria vermiculophylla.

    PubMed

    Nylund, Göran M; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  15. Computational reverse chemical ecology: Virtual screening and predicting behaviorally active semiochemicals for Bactrocera dorsalis

    PubMed Central

    2014-01-01

    Background Semiochemical is a generic term used for a chemical substance that influences the behaviour of an organism. It is a common term used in the field of chemical ecology to encompass pheromones, allomones, kairomones, attractants and repellents. Insects have mastered the art of using semiochemicals as communication signals and rely on them to find mates, host or habitat. This dependency of insects on semiochemicals has allowed chemical ecologists to develop environment friendly pest management strategies. However, discovering semiochemicals is a laborious process that involves a plethora of behavioural and analytical techniques, making it expansively time consuming. Recently, reverse chemical ecology approach using odorant binding proteins (OBPs) as target for elucidating behaviourally active compounds is gaining eminence. In this scenario, we describe a “computational reverse chemical ecology” approach for rapid screening of potential semiochemicals. Results We illustrate the high prediction accuracy of our computational method. We screened 25 semiochemicals for their binding potential to a GOBP of B. dorsalis using molecular docking (in silico) and molecular dynamics. Parallely, compounds were subjected to fluorescent quenching assays (Experimental). The correlation between in silico and experimental data were significant (r2 = 0.9408; P < 0.0001). Further, predicted compounds were subjected to behavioral bioassays and were found to be highly attractive to insects. Conclusions The present study provides a unique methodology for rapid screening and predicting behaviorally active semiochemicals. This methodology may be developed as a viable approach for prospecting active semiochemicals for pest control, which otherwise is a laborious process. PMID:24640964

  16. Activation of chemical promutagens by Selenastrum capricornutum in the plant cell/microbe coincubation assay

    SciTech Connect

    Gentile, J.M.; Lippert, M.; Johnson, P.; Shafer, T. )

    1990-05-01

    The critical balance of organisms living in aquatic environments is influenced by the presence and relationship of plants to those environments. However, even though plants occupy a fundamental trophic level within aquatic ecosystems, few studies have focused upon the effect of xenobiotics on aquatic plants, and even fewer studies have dealt with xenobiotic metabolism by aquatic plants. It is well established that plants can metabolize chemicals into mutagens. The impact of these unique plant-activated chemical mutagens on ecosystems, food chains and, ultimately, human health is an important question that will require intensive and integrative investigation. The plant cell/microbe coincubation assay is particularly advantageous for use with unicellular algae. The conditions of this assay are such that chemical metabolism and subsequent mutagen detection can be followed in intact algal cells under simulated field conditions. The purpose of this research was to demonstrate that a unicellular algal species could be used effectively in the plant cell/microbe coincubation assay to activate model chemical mutagens.

  17. [Advances in research of chemical constituents and pharmacological activities of common used spices].

    PubMed

    Sun, Chao-nan; Zhu, Yuan; Xu, Xi-ming; Yu, Jiang-nan

    2014-11-01

    Spices have enjoyed a long history and a worldwide application. Of particular interest is the pharmaceutical value of spices in addition to its basic seasoning function in cooking. Concretely, equipped with complex chemical compositions, spices are of significant importance in pharmacologic actions, like antioxidant, antibacterial, antitumor, as well as therapeutical effects in gastrointestinal disorders and cardiovascular disease. Although increasing evidences in support of its distinct role in the medical field has recently reported, little information is available for substantive, thorough and sophisticated researches on its chemical constituents and pharmacological activities, especially mechanism of these actions. Therefore, in popular wave of studies directed at a single spice, this review presents systematic studies on the chemical constituents and pharmacological activities associated with common used spices, together with current typical individual studies on functional mechanism, in order to pave the way for the exploitation and development of new medicines derived from the chemical compounds of spice (such as, piperine, curcumin, geniposide, cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic acid, crocin).

  18. Modeling the effect of water activity and storage temperature on chemical stability of coffee brews.

    PubMed

    Manzocco, Lara; Nicoli, Maria Cristina

    2007-08-08

    This work was addressed to study the chemical stability of coffee brew derivatives as a function of water activity (aw) and storage temperature. To this purpose, coffee brew was freeze-dried, equilibrated at increasing aw values, and stored for up to 10 months at different temperatures from -30 to 60 degrees C. The chemical stability of the samples was assessed by measuring H3O+ formation during storage. Independently of storage temperature, the rate of H3O+ formation was considerably low only when aw was reduced below 0.5 (94% w/w). Beyond this critical boundary, the rate increased, reaching a maximum value at ca. 0.8 aw (78% w/w). Further hydration up to the aw of the freshly prepared beverage significantly increased chemical stability. It was suggested that mechanisms other than lactones' hydrolysis, probably related to nonenzymatic browning pathways, could contribute to the observed increase in acidity during coffee staling. The temperature dependence of H3O+ formation was well-described by the Arrhenius equation in the entire aw range considered. However, aw affected the apparent activation energy and frequency factor. These effects were described by simple equations that were used to set up a modified Arrhenius equation. This model was validated by comparing experimental values, not used to generate the model, with those estimated by the model itself. The model allowed efficient prediction of the chemical stability of coffee derivatives on the basis of only the aw value and storage temperature.

  19. Chemical aspects of the trapping and recovery of uranium hexafluoride and fluorine during remediation activities

    SciTech Connect

    Del Cul, G.D.; Toth, L.M.

    1996-10-01

    Decontamination and decommission activities related to the Molten Salt Reactor Experiment (MSRE) involve the trapping and recovery of radiolitically generated uranium hexafluoride and fluorine. Although fission product radiolysis was known to generate F{sub 2}, the formation of UF{sub 6} and its transport from the fuel salt was unexpected. Some of these gaseous radiolysis products have been moving through the gas piping to a charcoal bed since the reactor was shut down in 1969. Current and planned remediation and clean-up activities involve the trapping of the gaseous products, deactivation and treatment of the activated charcoal bed, stabilization and reconditioning of the fuel salt, and recovery of the uranium. The chemical aspects of these processes, including radiolytic generation mechanisms, reactions between uranium hexafluoride and fluorine and trapping materials such as activated charcoal, activated alumina, and sodium fluoride, along with the analytical techniques used for the characterization of the materials and process control will be described.

  20. Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

    EPA Science Inventory

    Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eight...

  1. Redox activity and chemical interactions of metal oxide nano- and micro-particles with dithiothreitol (DTT).

    PubMed

    Nicolas, Johny; Jaafar, Malek; Sepetdjian, Elizabeth; Saad, Walid; Sioutas, Constantinos; Shihadeh, Alan; Saliba, Najat A

    2015-11-01

    The wide application and production of nanotechnology have increased the interest in studying the toxicity of nano- and micro-sized particles escaping into air from various aspects of the production process. Metal oxides (MOs) are one particular class of particles that exist abundantly in ambient PM. Studies show an emphasis on biological mechanisms by which inhalation exposure to MOs leads to disease. However, different biological assays provide different redox activity rankings making it difficult to assess the contributions of various MOs to measures of aggregate toxicity in multi-pollutant systems such as ambient PM. Therefore, research to evaluate the chemical interaction between these particles and molecules that are relevant to cellular redox activity can help in establishing indicators of reactivity. In particular, this study assesses the redox activity of six MOs mainly emitted from anthropogenic industrial activities using the dithiothreitol (DTT) assay. DTT is commonly used in acellular assays due to its analogous structure to cellular glutathione. The structural and chemical behaviors between active MOs and DTT were elucidated using FTIR, NMR, and BET methods. The results indicate that the health risk (redox activity) associated with MOs is mainly a function of their surface reactivity demonstrated by the ability of the oxidized (S-H) bond in DTT to form a stable bond with the MO surface.

  2. Chemical Constituents and Antimicrobial Activity of Indian Green Leafy Vegetable Cardiospermum halicacabum.

    PubMed

    Jeyadevi, R; Sivasudha, T; Ilavarasi, A; Thajuddin, N

    2013-06-01

    The present study was carried out to analyze chemical constituents and antibacterial activity of ethanolic leaf extract of Cardiospermum halicacabum (ECH). The FT-IR spectrum confirmed the presence of alcohols, phenols, alkanes, alkynes, aliphatic ester and flavonoids in ECH. The GC-MS analysis revealed that ECH contained about twenty four compounds. The major chemical compounds identified were cyclohexane-1, 4, 5-triol-3-one-1-carboxylic acid, benzene acetic acid, caryophyllene, phytol and neophytadiene. The ECH was screened for its antibacterial activity against different bacterial strains and anti fungal activity against Candida albicans by agar well diffusion and minimum inhibitory concentration (MIC) assay. ECH exhibited antibacterial and antifungal activity. All the tested bacterial strains showed MIC values ranging from 80 to 125 μg of extract/ml and C. albicans showed 190 μg of extract/ml as a MIC. The maximum activity ECH was observed against human pathogen Staphylococcus aureus followed by Escherichia coli and the fish pathogen Aeromonas hydrophila. ECH exhibited moderate activity against some of the tested multidrug resistant strains.

  3. Chemical composition and antimicrobial activity of the essential oils of Pistacia lentiscus var. chia.

    PubMed

    Magiatis, P; Melliou, E; Skaltsounis, A L; Chinou, I B; Mitaku, S

    1999-12-01

    The chemical composition of the three essential oils obtained by steam distillation of the mastic gum, leaves and twigs of Pistacia lentiscus var. chia, was studied by GC/MS. Sixty nine constituents were identified from the oils. alpha-Pinene, myrcene, trans-caryophyllene and germacrene D were found to be the major components. The in vitro antimicrobial activity of the three essential oils and of the resin (total, acid and neutral fraction) against six bacteria and three fungi is reported.

  4. Effect of chemical activation of 10% carbamide peroxide gel in tooth bleaching.

    PubMed

    Batista, Graziela Ribeiro; Arantes, Paula Tamiao; Attin, Thomas; Wiegand, Annette; Torres, Carlos Rocha

    2013-01-01

    This study aimed to evaluate the efficacy of chemical agents to increase the bleaching effectiveness of 10% carbamide peroxide. Two hundred and ninety enamel-dentin discs were prepared from bovine incisors. The color measurement was performed by a spectrophotometer using the CIE L*a*b*system. The groups were divided according to the bleaching treatment: negative control group (NC): without bleaching; positive control group (PC): bleached with 10% carbamide peroxide gel without any chemical activator; Manganese gluconate (MG); Manganese chloride (MC); Ferrous gluconate (FG); Ferric chloride (FC); and Ferrous sulphate (FS). Three different concentrations (MG, MC, FG, FC: 0.01, 0.02 and 0.03% w/w; FS: 0.001, 0.002 and 0.003% w/w) for each agent were tested. The bleaching gel was applied on the specimens for 8 h, after which they were immersed in artificial saliva for 16 h, during 14 days. Color assessments were made after 7 and 14 days. The data were analyzed by repeated measures analysis of variance and Tukey's test (5%). Generally, the test groups were unable to increase the bleaching effect (ΔE) significantly compared to the PC group. Only for ΔL, significant higher values compared to the PC group could be seen after 7 days in groups MG (0.02%), and FS (0.002 and 0.003%). The NC group showed significantly lower values than all tested groups. It was concluded that for home bleaching procedures, the addition of chemical activators did not produce a bleaching result significantly higher than the use of 10% carbamide peroxide without activation, and that the concentration of chemical activators used did not significantly influence the effectiveness of treatment.

  5. Modeling Joint Effects of Mixtures of Chemicals on Microorganisms Using Quantitative Structure Activity Relationships

    DTIC Science & Technology

    1993-08-22

    toxicity results from the 40 chemicals placed in the testing set were used to develop QSAR models. Molecular connectivity indexes were calculated for...Toxic Unit, Additivity Index , and Mixture Toxicity Index . The validity of these concepts was further verified using the results of the 8-component testing...standard deviation of 22.6. These variations are comparable to those reported by Blum (1989) for activated sludge cultures and Microtox , and may be

  6. Chemical Composition and Biological Activities of Fragrant Mexican Copal (Bursera spp.).

    PubMed

    Gigliarelli, Giulia; Becerra, Judith X; Curini, Massimo; Marcotullio, Maria Carla

    2015-12-12

    Copal is the Spanish word used to describe aromatic resins from several genera of plants. Mexican copal derives from several Bursera spp., Protium copal, some Pinus spp. (e.g., P. pseudostrobus) and a few Fabaceae spp. It has been used for centuries as incense for religious ceremonies, as a food preservative, and as a treatment for several illnesses. The aim of this review is to analyze the chemical composition and biological activity of commercial Mexican Bursera copal.

  7. Effect of TBT and PAHs on CYP1A, AhR and Vitellogenin Gene Expression in the Japanese Eel, Anguilla japonica.

    PubMed

    Choi, Min Seop; Kwon, Se Ryun; Choi, Seong Hee; Kwon, Hyuk Chu

    2012-12-01

    Gene expressions of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor (AhR) and vitellogenin (Vg) by endocrine disruptors, benzo[α]pyrene (B[a]P) and tributyltin (TBT) were examined in cultured eel hepatocytes which were isolated from eels treated previously with B[a]P (10 mg/kg) or estradiol-17β (20 mg/kg) in vivo, and the relationship between CYP1A, AhR and Vg genes were studied. When the cultured eel hepatocytes were treated with B[a]P (10(-6)-10(-5) M) the gene expressions of CYP1A and AhR were enhanced in a concentration-dependent manner. However, when treated with TBT (10(-9)-10(-5) M) the gene expressions of CYP1A and AhR were suppressed at high concentrations (10(-6)-10(-5) M), while having no effects at low concentrations (10(-9)-10(-7) M). Gene expression of Vg was also suppressed by TBT in a concentration-dependent manner in cultured eel hepatocytes which was previously treated in vivo with estradiol-17β.

  8. Preparation of porous bio-char and activated carbon from rice husk by leaching ash and chemical activation.

    PubMed

    Ahiduzzaman, Md; Sadrul Islam, A K M

    2016-01-01

    Preparation porous bio-char and activated carbon from rice husk char study has been conducted in this study. Rice husk char contains high amount silica that retards the porousness of bio-char. Porousness of rice husk char could be enhanced by removing the silica from char and applying heat at high temperature. Furthermore, the char is activated by using chemical activation under high temperature. In this study no inert media is used. The study is conducted at low oxygen environment by applying biomass for consuming oxygen inside reactor and double crucible method (one crucible inside another) is applied to prevent intrusion of oxygen into the char. The study results shows that porous carbon is prepared successfully without using any inert media. The adsorption capacity of material increased due to removal of silica and due to the activation with zinc chloride compared to using raw rice husk char. The surface area of porous carbon and activated carbon are found to be 28, 331 and 645 m(2) g(-1) for raw rice husk char, silica removed rice husk char and zinc chloride activated rice husk char, respectively. It is concluded from this study that porous bio-char and activated carbon could be prepared in normal environmental conditions instead of inert media. This study shows a method and possibility of activated carbon from agro-waste, and it could be scaled up for commercial production.

  9. Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells.

    PubMed

    Tanaka, Go; Kanaji, Sachiko; Hirano, Ayumi; Arima, Kazuhiko; Shinagawa, Akira; Goda, Chiho; Yasunaga, Shin'ichiro; Ikizawa, Koichi; Yanagihara, Yukiyoshi; Kubo, Masato; Kuriyama-Fujii, Yoshiaki; Sugita, Yuji; Inokuchi, Akira; Izuhara, Kenji

    2005-06-01

    It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.

  10. Chemical composition and biological activity of ripe pumpkin fruits (Cucurbita pepo L.) cultivated in Egyptian habitats.

    PubMed

    Badr, Sherif E A; Shaaban, Mohamed; Elkholy, Yehya M; Helal, Maher H; Hamza, Akila S; Masoud, Mohamed S; El Safty, Mounir M

    2011-09-01

    The chemical composition and biological activity of three parts (rind, flesh and seeds) of pumpkin fruits (Cucurbita pepo L.) cultivated in Egypt were studied. Chemical analysis of fibre, protein, β-carotene, carbohydrates, minerals and fatty acids present in the rind, flesh, seeds and defatted seeds meal was conducted. Chemical, GC-MS and biological assays of organic extracts of the main fruit parts, rind and flesh established their unique constituents. Chromatographic purification of the extracts afforded triglyceride fatty acid mixture (1), tetrahydro-thiophene (2), linoleic acid (3), calotropoleanly ester (4), cholesterol (5) and 13(18)-oleanen-3-ol (6). GC-MS analysis of the extract's unpolar fraction revealed the existence of dodecane and tetradecane. Structures of the isolated compounds (1-6) were confirmed by NMR and EI-MS spectrometry. Antimicrobial, antiviral and antitumour activities of the fruit parts were discussed. The promising combined extract of rind and flesh was biologically studied for microbial and cytotoxic activities in comparison with the whole isolated components.

  11. Synthesis of sulfonated porous carbon nanospheres solid acid by a facile chemical activation route

    SciTech Connect

    Chang, Binbin Guo, Yanzhen; Yin, Hang; Zhang, Shouren; Yang, Baocheng

    2015-01-15

    Generally, porous carbon nanospheres materials are usually prepared via a template method, which is a multi-steps and high-cost strategy. Here, we reported a porous carbon nanosphere solid acid with high surface area and superior porosity, as well as uniform nanospheical morphology, which prepared by a facile chemical activation with ZnCl{sub 2} using resorcinol-formaldehyde (RF) resins spheres as precursor. The activation of RF resins spheres by ZnCl{sub 2} at 400 °C brought high surface area and large volume, and simultaneously retained numerous oxygen-containing and hydrogen-containing groups due to the relatively low processing temperature. The presence of these functional groups is favorable for the modification of –SO{sub 3}H groups by a followed sulfonation treating with sulphuric acid and organic sulfonic acid. The results of N{sub 2} adsorption–desorption and electron microscopy clearly showed the preservation of porous structure and nanospherical morphology. Infrared spectra certified the variation of surface functional groups after activation and the successful modification of –SO{sub 3}H groups after sulfonation. The acidities of catalysts were estimated by an indirect titration method and the modified amount of –SO{sub 3}H groups were examined by energy dispersive spectra. The results suggested sulfonated porous carbon nanospheres catalysts possessed high acidities and –SO{sub 3}H densities, which endowed their significantly catalytic activities for biodiesel production. Furthermore, their excellent stability and recycling property were also demonstrated by five consecutive cycles. - Graphical abstract: Sulfonated porous carbon nanospheres with high surface area and superior catalytic performance were prepared by a facile chemical activation route. - Highlights: • Porous carbon spheres solid acid prepared by a facile chemical activation. • It owns high surface area, superior porosity and uniform spherical morphology. • It possesses

  12. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    SciTech Connect

    Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia R.; Woodin, Bruce; Stegeman, John J.

    2012-12-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC{sub 50} values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells. -- Highlights: ► PCB126 caused cellular changes in the developing swim bladder. ► Swim bladder inflation was not related to expression of CYP1 or cox

  13. Omani propolis: chemical profiling, antibacterial activity and new propolis plant sources

    PubMed Central

    2013-01-01

    Background Propolis (bee glue) is a resinous honeybee product having a long history of application in many countries as a traditional remedy for treating wounds, burns, soar throat, stomach disorders, etc. It has been proved to possess beneficial biological effects, including antimicrobial, antioxidant, anti-inflammatory, cytotoxic, antiulcer, and many others. Bees gather propolis from diverse resinous plant parts and in different phytogeographic regions its chemical composition might vary significantly. In this article we report the results of the first study on the chemical profiles of propolis from Oman, its plant origin and antibacterial activity. Results The chemical profiles of Omani propolis extracts were obtained by GC-MS analysis after silylation. Over 50 individual compounds were identified in the samples, belonging to different compound types: sugars, polyols, hydroxy acids, fatty acids, cardanols and cardols, anacardic acids, flavan derivatives, triterpenes, prenylated flavanones and chalcones. The profiles were dissimilar from other known propolis types. They demonstrate that although Oman is not a large country, the plant sources of propolis vary significantly, even in the same apiary and the same season. Based on chemical profiles, and isolation and identification of major marker compounds (new propolis constituents), new plant sources of propolis were found: Azadiracta indica (neem tree) and Acacia spp. (most probably A. nilotica). The ethanol extracts of the studied propolis samples demonstrated activity against S. aureus (MIC < 100 μg. mL-1) and E. coli (MIC < 380 μg. mL-1). Conclusion Omani propolis is different form the known propolis types and demonstrates significant chemical diversity. Its most important plant source is the resin of Azadirachta indica, and as a result its typical components are С5-prenyl flavanones. Other plant sources have been identified, too, playing some role in resin collection by bees in Oman: Acacia spp

  14. Chemical graphs, molecular matrices and topological indices in chemoinformatics and quantitative structure-activity relationships.

    PubMed

    Ivanciuc, Ovidiu

    2013-06-01

    Chemical and molecular graphs have fundamental applications in chemoinformatics, quantitative structureproperty relationships (QSPR), quantitative structure-activity relationships (QSAR), virtual screening of chemical libraries, and computational drug design. Chemoinformatics applications of graphs include chemical structure representation and coding, database search and retrieval, and physicochemical property prediction. QSPR, QSAR and virtual screening are based on the structure-property principle, which states that the physicochemical and biological properties of chemical compounds can be predicted from their chemical structure. Such structure-property correlations are usually developed from topological indices and fingerprints computed from the molecular graph and from molecular descriptors computed from the three-dimensional chemical structure. We present here a selection of the most important graph descriptors and topological indices, including molecular matrices, graph spectra, spectral moments, graph polynomials, and vertex topological indices. These graph descriptors are used to define several topological indices based on molecular connectivity, graph distance, reciprocal distance, distance-degree, distance-valency, spectra, polynomials, and information theory concepts. The molecular descriptors and topological indices can be developed with a more general approach, based on molecular graph operators, which define a family of graph indices related by a common formula. Graph descriptors and topological indices for molecules containing heteroatoms and multiple bonds are computed with weighting schemes based on atomic properties, such as the atomic number, covalent radius, or electronegativity. The correlation in QSPR and QSAR models can be improved by optimizing some parameters in the formula of topological indices, as demonstrated for structural descriptors based on atomic connectivity and graph distance.

  15. [Advances on investigation of chemical constituents, pharmacological activities and clinical applications of Capparis spinosa].

    PubMed

    Yang, Tao; Liu, Yu-Qing; Wang, Chang-Hong; Wang, Zheng-Tao

    2008-11-01

    In this paper, the chemical constituents, pharmacological activities and clinical applications of Capparis spinosa had been reviewed. The constituents of C. spinosa include the saccharides and glycosides, flavonoids, alkaloids, terpenoids and volatile oils, fatty acids and steroides and so on. C. spinosa had many extensive pharmacological effects such as anti-inflammatory, odynolysis, antifungus, hepatoprotective effect, hypoglycemic activity, antioxidation, anti-hyperlipemia, anticoagulated blood, smooth muscle stimulation, anti-stress reaction, improve memory. It was used to treat arthrolithiasis, rheumarthritis and dermatosis in clinic in domestic, and it would have a broad application prospects.

  16. Activation of chemicals into mutagens by green plants: a preliminary discussion.

    PubMed Central

    Plewa, M J

    1978-01-01

    This paper is a review of recent studies that demonstrate the activation of chemicals (especially pesticides into mutagens by green plants. Such activation of pesticides may be hazardous to the public health because of their widespread use in agriculture and the current lack of information that exists about such processes. The mutagenic properties of the s-triazine herbicides (atrazine, simazine, and cyanazine) as exhibited in various assay systems are discussed. In vivo, in vitro, and in situ plant assays are presented, and the maize wx locus assay is discussed. PMID:367774

  17. An Update on Oligosaccharides and Their Esters from Traditional Chinese Medicines: Chemical Structures and Biological Activities

    PubMed Central

    Chen, Xiang-Yang; Wang, Ru-Feng; Liu, Bin

    2015-01-01

    A great number of naturally occurring oligosaccharides and oligosaccharide esters have been isolated from traditional Chinese medicinal plants, which are used widely in Asia and show prominent curative effects in the prevention and treatment of kinds of diseases. Numerous in vitro and in vivo experiments have revealed that oligosaccharides and their esters exhibited various activities, including antioxidant, antidepressant, cytotoxic, antineoplastic, anti-inflammatory, neuroprotective, cerebral protective, antidiabetic, plant growth-regulatory, and immunopotentiating activities. This review summarizes the investigations on the distribution, chemical structures, and bioactivities of natural oligosaccharides and their esters from traditional Chinese medicines between 2003 and 2013. PMID:25861364

  18. High surface area activated carbon prepared from cassava peel by chemical activation.

    PubMed

    Sudaryanto, Y; Hartono, S B; Irawaty, W; Hindarso, H; Ismadji, S

    2006-03-01

    Cassava is one of the most important commodities in Indonesia, an agricultural country. Cassava is one of the primary foods in our country and usually used for traditional food, cake, etc. Cassava peel is an agricultural waste from the food and starch processing industries. In this study, this solid waste was used as the precursor for activated carbon preparation. The preparation process consisted of potassium hydroxide impregnation at different impregnation ratio followed by carbonization at 450-750 degrees C for 1-3 h. The results revealed that activation time gives no significant effect on the pore structure of activated carbon produced, however, the pore characteristic of carbon changes significantly with impregnation ratio and carbonization temperature. The maximum surface area and pore volume were obtained at impregnation ratio 5:2 and carbonization temperature 750 degrees C.

  19. Chemical composition and antibacterial activity of essential oils from the Tunisian Allium nigrum L.

    PubMed Central

    Rouis-Soussi, Lamia Sakka; Ayeb-Zakhama, Asma El; Mahjoub, Aouni; Flamini, Guido; Jannet, Hichem Ben; Harzallah-Skhiri, Fethia

    2014-01-01

    The chemical composition of the essential oils of different Allium nigrum L. organs and the antibacterial activity were evaluated. The study is particularly interesting because hitherto there are no reports on the antibacterial screening of this species with specific chemical composition. Therefore, essential oils from different organs (flowers, stems, leaves and bulbs) obtained separately by hydrodistillation were analyzed using gas chromatography–mass spectrometry (GC–MS). The antibacterial activity was evaluated using the disc and microdilution assays. In total, 39 compounds, representing 90.8-96.9 % of the total oil composition, were identified. The major component was hexadecanoic acid (synonym: palmitic acid) in all the A. nigrum organs oils (39.1-77.2 %). We also noted the presence of some sesquiterpenes, mainly germacrene D (12.8 %) in leaves oil) and some aliphatic compounds such as n-octadecane (30.5 %) in bulbs oil. Isopentyl isovalerate, 14-oxy-α-muurolene and germacrene D were identified for the first time in the genus Allium L. All the essential oils exhibited antimicrobial activity, especially against Enterococcus faecalis and Staphylococcus aureus. The oil obtained from the leaves exhibited an interesting antibacterial activity, with a Minimum Inhibitory Concentration (MIC) of 62.50 µg/mL against these two latter strains. The findings showed that the studied oils have antibacterial activity, and thus great potential for their application in food preservation and natural health products. PMID:26417280

  20. Chemical composition and antibacterial activity of essential oils from the Tunisian Allium nigrum L.

    PubMed

    Rouis-Soussi, Lamia Sakka; Ayeb-Zakhama, Asma El; Mahjoub, Aouni; Flamini, Guido; Jannet, Hichem Ben; Harzallah-Skhiri, Fethia

    2014-01-01

    The chemical composition of the essential oils of different Allium nigrum L. organs and the antibacterial activity were evaluated. The study is particularly interesting because hitherto there are no reports on the antibacterial screening of this species with specific chemical composition. Therefore, essential oils from different organs (flowers, stems, leaves and bulbs) obtained separately by hydrodistillation were analyzed using gas chromatography-mass spectrometry (GC-MS). The antibacterial activity was evaluated using the disc and microdilution assays. In total, 39 compounds, representing 90.8-96.9 % of the total oil composition, were identified. The major component was hexadecanoic acid (synonym: palmitic acid) in all the A. nigrum organs oils (39.1-77.2 %). We also noted the presence of some sesquiterpenes, mainly germacrene D (12.8 %) in leaves oil) and some aliphatic compounds such as n-octadecane (30.5 %) in bulbs oil. Isopentyl isovalerate, 14-oxy-α-muurolene and germacrene D were identified for the first time in the genus Allium L. All the essential oils exhibited antimicrobial activity, especially against Enterococcus faecalis and Staphylococcus aureus. The oil obtained from the leaves exhibited an interesting antibacterial activity, with a Minimum Inhibitory Concentration (MIC) of 62.50 µg/mL against these two latter strains. The findings showed that the studied oils have antibacterial activity, and thus great potential for their application in food preservation and natural health products.

  1. Design, in vitro stability, and ocular hypotensive activity of t-butalone chemical delivery systems.

    PubMed

    Reddy, I K; Vaithiyalingam, S R; Khan, M A; Bodor, N S

    2001-08-01

    The objective of this work was to synthesize two bioreversible diacyl derivatives of t-butalone (chemical delivery systems), determine their chemical and in vitro stability, and investigate their potential use as topical antiglaucoma agents. The stability of these compounds was determined in isotonic phosphate buffers (pH range 5-8) and in selected biological media, including human whole blood, rabbit and rat blood, and the anterior segment tissues of rabbit. The ocular hypotensive activity of these compounds in unrestrained, normotensive albino rabbits was determined with a pneumatonometer. The two compounds were stable at lower pH. The stability decreased as the pH increased, suggesting their lability to base-catalyzed hydrolysis. These compounds exhibited significant differences in the hydrolytic rates in the whole blood among species examined (rat > rabbit > human). The observed rates of disappearance in different ocular tissues were indicative of relative enzyme activity in these media (iris-ciliary body > cornea > aqueous humor). The two compounds exhibited a significant ocular hypotensive activity (P < 0.01) at 2% dose level. The peak activity was found between 2 and 4 h, and the activity was maintained for 4.5 to 7 h. The dipivalyl derivative of t-butalone exhibited more pronounced decrease in intraocular pressure than that of diisovaleryl derivative. The present study suggests the possible use of diacyl derivatives of t-butalone as ocular hypotensive agents.

  2. Chemically and biologically modified activated carbon sorbents for the removal of lead ions from aqueous media.

    PubMed

    Mahmoud, Mohamed E; Abdel-Fattah, Tarek M; Osman, Maher M; Ahmed, Somia B

    2012-01-01

    A method is described for hybridization of the adsorption and biosorption characteristics of chemically treated commercial activated carbon and baker's yeast, respectively, for the formation of environmental friendly multifunctional sorbents. Activated carbon was loaded with baker's yeast after acid-base treatment. Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) Spectroscopy were used to characterize these sorbents. Moreover, the sorption capabilities for lead (II) ions were evaluated. A value of 90 μmol g(-1) was identified as the maximum sorption capacity of activated carbon. Acid-base treatment of activated carbon was found to double the sorption capacity (140-180 μmol g(-1)). Immobilization of baker's yeast on the surface of activated carbon sorbents was found to further improve the sorption capacity efficiency of lead to 360, 510 and 560 μmol g(-1), respectively. Several important factors such as pH, contact time, sorbent dose, lead concentration and interfering ions were examined. Lead sorption process was studied and evaluated by several adsorption isotherms and found to follow the Langmuir and BET models. The potential applications of various chemically and biologically modified sorbents and biosorbents for removal of lead from real water matrices were also investigated via multistage micro-column technique and the results referred to excellent recovery values of lead (95.0-99.0 ± 3.0-5.0 %).

  3. Eupatorium capillifolium essential oil: chemical composition antifungal activity and insecticidal activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural plant extracts often contain compounds that are useful in pest management applications. The essential oil of Eupatorium capillifolium (dog-fennel) was investigated for antifungal and insecticidal activities. Essential oil obtained by hydrodistillation of aerial parts was analyzed by gas chro...

  4. Regulation of Ahr signaling by Nrf2 during development: Effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio).

    PubMed

    Rousseau, Michelle E; Sant, Karilyn E; Borden, Linnea R; Franks, Diana G; Hahn, Mark E; Timme-Laragy, Alicia R

    2015-10-01

    The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and has been reported to involve oxidative stress. Ahr participates in crosstalk with another transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding domain in Nrf2a (nrf2a(fh318/fh318)), rendering these embryos more sensitive to oxidative stress. Embryos were exposed to 2 nM or 5 nM PCB126 at 24 h post fertilization (prim-5 stage of pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf; protruding - mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126 toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental differences from wildtype embryos, including delayed inflation of the swim bladder and smaller yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a, keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM). Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2, NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1), showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This study elucidates the interaction between two important transcription factor pathways in the developmental toxicity of co-planar PCBs.

  5. Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance

    PubMed Central

    Frank, Kristi L.; Vergidis, Paschalis; Brinkman, Cassandra L.; Greenwood Quaintance, Kerryl E.; Barnes, Aaron M. T.; Mandrekar, Jayawant N.; Schlievert, Patrick M.; Dunny, Gary M.; Patel, Robin

    2015-01-01

    Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype. PMID:26076451

  6. Chemical composition and genotoxic activity of petroleum derivatives collected in two working environments

    SciTech Connect

    Pasquini, R.; Taningher, M.; Monarca, S.; Pala, M.; Angeli, G.

    1989-01-01

    Pitch and bitumen, two complex petroleum derivative mixtures, were studied for both their chemical composition and their mutagenic/DNA damaging activity. While bitumen revealed no genotoxic effect and low polycyclic aromatic hydrocarbons (PAHs) concentration, petroleum pitch showed a high concentration of mutagenic/carcinogenic PAHs, and also an elevated mutagenic activity when assayed by the Ames test, in the presence of postmitochondrial rat liver fractions. The in vitro mutagenic activity was detectable as frameshift mutation by assaying the pitch both as an in toto mixture and after HPLC fractionation, the most polar fractions being the most active. In contrast, both derivatives showed no in vivo DNA damage in rat liver, using the DNA alkaline elution technique and the fluorometric assay of DNA unwinding.

  7. Chemical composition, antimicrobial and antioxidant activities of essential oils from organically cultivated fennel cultivars.

    PubMed

    Shahat, Abdelaaty A; Ibrahim, Abeer Y; Hendawy, Saber F; Omer, Elsayed A; Hammouda, Faiza M; Abdel-Rahman, Fawzia H; Saleh, Mahmoud A

    2011-02-01

    Essential oils of the fruits of three organically grown cultivars of Egyptian fennel (Foeniculum vulgare var. azoricum, Foeniculum vulgare var. dulce and Foeniculum vulgare var. vulgare) were examined for their chemical constituents, antimicrobial and antioxidant activities. Gas chromatography/mass spectrometry analysis of the essential oils revealed the presence of 18 major monoterpenoids in all three cultivars but their percentage in each oil were greatly different. trans-Anethole, estragole, fenchone and limonene were highly abundant in all of the examined oils. Antioxidant activities of the essential oils were evaluated using the DPPH radical scavenging, lipid peroxidation and metal chelating assays. Essential oils from the azoricum and dulce cultivars were more effective antioxidants than that from the vulgare cultivar. Antimicrobial activities of each oil were measured against two species of fungi, two species of Gram negative and two species of Gram positive bacteria. All three cultivars showed similar antimicrobial activity.

  8. Chemical acceleration of a neutral granulated blast-furnace slag activated by sodium carbonate

    SciTech Connect

    Kovtun, Maxim Kearsley, Elsabe P. Shekhovtsova, Julia

    2015-06-15

    This paper presents results of a study on chemical acceleration of a neutral granulated blast-furnace slag activated using sodium carbonate. As strength development of alkali-activated slag cements containing neutral GBFS and sodium carbonate as activator at room temperature is known to be slow, three accelerators were investigated: sodium hydroxide, ordinary Portland cement and a combination of silica fume and slaked lime. In all cements, the main hydration product is C–(A)–S–H, but its structure varies between tobermorite and riversideite depending on the accelerator used. Calcite and gaylussite are present in all systems and they were formed due to either cation exchange reaction between the slag and the activator, or carbonation. With accelerators, compressive strength up to 15 MPa can be achieved within 24 h in comparison to 2.5 MPa after 48 h for a mix without an accelerator.

  9. Ascaroside activity in Caenorhabditis elegans is highly dependent on chemical structure.

    PubMed

    Hollister, Kyle A; Conner, Elizabeth S; Zhang, Xinxing; Spell, Mark; Bernard, Gary M; Patel, Pratik; de Carvalho, Ana Carolina G V; Butcher, Rebecca A; Ragains, Justin R

    2013-09-15

    The nematode Caenorhabditis elegans secretes ascarosides, structurally diverse derivatives of the 3,6-dideoxysugar ascarylose, and uses them in chemical communication. At high population densities, specific ascarosides, which are together known as the dauer pheromone, trigger entry into the stress-resistant dauer larval stage. In order to study the structure-activity relationships for the ascarosides, we synthesized a panel of ascarosides and tested them for dauer-inducing activity. This panel includes a number of natural ascarosides that were detected in crude pheromone extract, but as yet have no assigned function, as well as many unnatural ascaroside derivatives. Most of these ascarosides, some of which have significant structural similarity to the natural dauer pheromone components, have very little dauer-inducing activity. Our results provide a primer to ascaroside structure-activity relationships and suggest that slight modifications to ascaroside structure dramatically influence binding to the relevant G protein-coupled receptors that control dauer formation.

  10. Ascaroside activity in Caenorhabditis elegans is highly dependent on chemical structure

    PubMed Central

    Hollister, Kyle A.; Conner, Elizabeth S.; Zhang, Xinxing; Spell, Mark; Bernard, Gary M.; Patel, Pratik; de Carvalho, Ana Carolina G.V.; Butcher, Rebecca A.; Ragains, Justin R.

    2015-01-01

    The nematode Caenorhabditis elegans secretes ascarosides, structurally diverse derivatives of the 3,6-dideoxysugar ascarylose, and uses them in chemical communication. At high population densities, specific ascarosides, which are together known as the dauer pheromone, trigger entry into the stress-resistant dauer larval stage. In order to study the structure-activity relationships for the ascarosides, we synthesized a panel of ascarosides and tested them for dauer-inducing activity. This panel includes a number of natural ascarosides that were detected in crude pheromone extract, but as yet have no assigned function, as well as many unnatural ascaroside derivatives. Most of these ascarosides, some of which have significant structural similarity to the natural dauer pheromone components, have very little dauer-inducing activity. Our results provide a primer to ascaroside structure-activity relationships and suggest that slight modifications to ascaroside structure dramatically influence binding to the relevant G protein-coupled receptors that control dauer formation. PMID:23920482

  11. Chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from Cymbopogon nardus L.

    PubMed

    Muhd Haffiz, J; Norhayati, I; Getha, K; Nor Azah, M A; Mohd Ilham, A; Lili Sahira, H; Roshan Jahn, M S; Muhd Syamil, A

    2013-03-01

    Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis.

  12. Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity.

    PubMed

    Yang, Yi-Xi; An, Mao-Mao; Jin, Yong-Sheng; Chen, Hai-Sheng

    2017-01-01

    A new compounds neopaleaceolactoside (1), along with nine known compounds phyllocoumarin (2), quercetin (3), quercitrin (4), quercetin-3-methyl ether (5), vincetoxicoside B (6), isoquercitrin (7), kaempferol (8), (-)-epicatechin (9), and chlorogenic acid (10), was isolated from Polygonum paleaceum Wall. Their chemical structures were established based on one-dimensional and two-dimensional nuclear magnetic resonance techniques, mass spectrometry and by comparison with spectroscopic data reported. Some selected compounds were screened for their antifungal activity. Quercetin (3), vincetoxicoside B (6), kaempferol (8), and (-)-epicatechin (9) showed synergistic antifungal activities with the FICI values <0.5. A preliminary structure-activity relationship could be observed that free 3-OH in the structure of flavonoids was important for synergistic antifungal activity.

  13. Optimization of nickel adsorption from aqueous solution by using activated carbon prepared from waste apricot by chemical activation

    NASA Astrophysics Data System (ADS)

    Erdoğan, S.; Önal, Y.; Akmil-Başar, C.; Bilmez-Erdemoğlu, S.; Sarıcı-Özdemir, Ç.; Köseoğlu, E.; İçduygu, G.

    2005-12-01

    Waste apricot supplied by Malatya apricot plant (Turkey) was activated by using chemical activation method and K 2CO 3 was chosen for this purpose. Activation temperature was varied over the temperature range of 400-900 °C and N 2 atmosphere was used with 10 °C/min heat rate. The maximum surface area (1214 m 2/g) and micropore volume (0.355 cm 3/g) were obtained at 900 °C, but activated carbon was predominantly microporous at 700 °C. The resulting activated carbons were used for removal of Ni(II) ions from aqueous solution and adsorption properties have been investigated under various conditions such as pH, activation temperature, adsorbent dosage and nickel concentration. Adsorption parameters were determined by using Langmuir model. Optimal condition was determined as; pH 5, 0.7 g/10 ml adsorbent dosage, 10 mg/l Ni(II) concentration and 60 min contact time. The results indicate that the effective uptake of Ni(II) ions was obtained by activating the carbon at 900 °C.

  14. Chemical reactivity and biological activity of chalcones and other α,β-unsaturated carbonyl compounds.

    PubMed

    Maydt, Daniela; De Spirt, Silke; Muschelknautz, Christian; Stahl, Wilhelm; Müller, Thomas J J

    2013-08-01

    Abstract 1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction. 2. The present study used a model system estimating the reactivity of different synthetic chalcones and other α,β-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts. 3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5'-dithiobis-(2-nitrobenzoic acid) and followed