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Sample records for ah receptor-dependent gene

  1. Glucocorticoid receptor-dependent gene regulatory networks.

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    Phillip Phuc Le

    2005-08-01

    Full Text Available While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expression profile of mouse livers in the presence or absence of exogenous glucocorticoid, resulting in over 1,300 differentially expressed genes. We then executed genome-wide location analysis on chromatin from the same livers, identifying more than 300 promoters that are bound by the GR. Intersecting the two lists yielded 53 genes whose expression is functionally dependent upon the ligand-bound GR. Further network and sequence analysis of the functional targets enabled us to suggest interactions between the GR and other transcription factors at specific target genes. Together, our results further our understanding of the GR and its targets, and provide the basis for more targeted glucocorticoid therapies.

  2. Induction of AhR-mediated gene transcription by coffee.

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    Ishikawa, Toshio; Takahashi, Satoshi; Morita, Koji; Okinaga, Hiroko; Teramoto, Tamio

    2014-01-01

    Aryl hydrocarbon receptor (AhR) is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells. HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS) or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses. All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum. By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health.

  3. Induction of AhR-mediated gene transcription by coffee.

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    Toshio Ishikawa

    Full Text Available Aryl hydrocarbon receptor (AhR is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs. Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells.HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses.All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum.By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health.

  4. Progesterone receptor-dependent regulation of genes in the oviducts of female mice.

    Science.gov (United States)

    Akison, Lisa K; Boden, Michael J; Kennaway, David J; Russell, Darryl L; Robker, Rebecca L

    2014-08-15

    Oviducts play a critical role in gamete and embryo transport, as well as supporting early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while its activating ligand, progesterone, surges to peak levels as ovulation approaches. Progesterone is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR null mice to identify genes potentially regulated by PGR in the oviducts during the periovulatory period. Histologically, oviducts from PGR null mice showed no gross structural or morphological defects compared with normal littermates. However, microarray analysis of oviducts at 8 h posthuman chorionic gonadotropin revealed >1,000 PGR-dependent genes. Using reverse-transcription polymerase chain reaction (RT-PCR) we selected 10 genes for validation based on their potential roles in oocyte/embryo transport and support. Eight genes were confirmed to be downregulated (Adamts1, Itga8, Edn3, Prlr, Ptgfr, Des, Myocd, and Actg2) and one upregulated (Agtr2) in PGR null oviducts. Expression of these genes was also assessed in oviducts of naturally cycling mice during ovulation and day 1 and day 4 of pregnancy. Adamts1, Itga8, Edn3, Prlr, and Ptgfr were significantly upregulated in oviducts at ovulation/mating. However, most genes showed basal levels of expression at other times. The exceptions were Prlr and Ptgfr, which showed pulsatile increases on day 1 and/or day 4 of pregnancy. This is the first, comprehensive study to elucidate putative PGR-regulated genes in the oviduct and reveals key downstream targets potentially mediating oocyte and embryo transport. Copyright © 2014 the American Physiological Society.

  5. PLK1 Signaling in Breast Cancer Cells Cooperates with Estrogen Receptor-Dependent Gene Transcription

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    Michael Wierer

    2013-06-01

    Full Text Available Polo-like kinase 1 (PLK1 is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 mediates estrogen receptor (ER-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. Performing large-scale phosphoproteomics of estradiol-treated MCF7 cells in the presence or absence of the specific PLK1 inhibitor BI2536, we identified several PLK1 end targets involved in transcription, including the histone H3K4 trimethylase MLL2, the function of which on ER target genes was impaired by PLK1 inhibition. Our results propose a mechanism for the tumor-suppressive role of PLK1 in mammals as an interphase transcriptional regulator.

  6. Ron receptor-dependent gene regulation of Kupffer cells during endotoxemia

    Institute of Scientific and Technical Information of China (English)

    Rishikesh M Kulkarni

    2014-01-01

    BACKGROUND: Ron  receptor  tyrosine  kinase  signaling  in macrophages, including Kupffer cells and alveolar macrophages, suppresses  endotoxin-induced  proinlfammatory  cytokine/chemokine production. Further, we have also identiifed genes from Ron replete and Ron deplete livers that were differentially expressed  during  the  progression  of  liver  inlfammation associated with acute liver failure in mice by microarray analyses. While  important  genes  and  signaling  pathways  have  been identiifed downstream of Ron signaling during progression of inlfammation by this approach, the precise role that Ron receptor plays in regulating the transcriptional landscape in macrophages, and particular in isolated Kupffer cells, has still not been investigated. METHODS: Kupffer cells were isolated from wild-type (TK+/+) and Ron tyrosine kinase deifcient (TK-/-) mice. Ex vivo, the cells were treated with lipopolysaccharide (LPS) in the presence or absence of the Ron ligand, hepatocyte growth factor-like protein (HGFL). Microarray and qRT-PCR analyses were utilized to identify alterations in gene expression between genotypes. RESULTS: Microarray  analyses  identiifed  genes  expressed differentially in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment. Interestingly, our studies identiifed Mefv, a gene that codes for the anti-inlfammatory protein pyrin, as an HGFL-stimulated Ron-dependent gene. Moreover, lipocalin 2, a proinlfammatory gene, which is induced by  LPS,  was  signiifcantly  suppressed  by  HGFL  treatment. Microarray  results

  7. Functional conservation and divergence of four ginger AP1/AGL9 MADS-box genes revealed by analysis of their expression and protein-protein interaction, and ectopic expression of AhFUL gene in Arabidopsis.

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    Xiumei Li

    Full Text Available Alpinia genus are known generally as ginger-lilies for showy flowers in the ginger family, Zingiberaceae, and their floral morphology diverges from typical monocotyledon flowers. However, little is known about the functions of ginger MADS-box genes in floral identity. In this study, four AP1/AGL9 MADS-box genes were cloned from Alpinia hainanensis, and protein-protein interactions (PPIs and roles of the four genes in floral homeotic conversion and in floral evolution are surveyed for the first time. AhFUL is clustered to the AP1 lineage, AhSEP4 and AhSEP3b to the SEP lineage, and AhAGL6-like to the AGL6 lineage. The four genes showed conserved and divergent expression patterns, and their encoded proteins were localized in the nucleus. Seven combinations of PPI (AhFUL-AhSEP4, AhFUL-AhAGL6-like, AhFUL-AhSEP3b, AhSEP4-AhAGL6-like, AhSEP4-AhSEP3b, AhAGL6-like-AhSEP3b, and AhSEP3b-AhSEP3b were detected, and the PPI patterns in the AP1/AGL9 lineage revealed that five of the 10 possible combinations are conserved and three are variable, while conclusions cannot yet be made regarding the other two. Ectopic expression of AhFUL in Arabidopsis thaliana led to early flowering and floral organ homeotic conversion to sepal-like or leaf-like. Therefore, we conclude that the four A. hainanensis AP1/AGL9 genes show functional conservation and divergence in the floral identity from other MADS-box genes.

  8. Transcript variations, phylogenetic tree and chromosomal localization of porcine aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) genes

    Indian Academy of Sciences (India)

    AGNIESZKA SADOWSKA; LUKASZ PAUKSZTO; ANNA NYNCA; IZABELA SZCZERBAL; KARINA ORLOWSKA; SYLWIA SWIGONSKA; MONIKA RUSZKOWSKA; TOMASZ MOLCAN; JAN P. JASTRZEBSKI; GRZEGORZ PANASIEWICZ; RENATA E. CIERESZKO

    2017-03-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor best known for mediating xenobiotic-induced toxicity. AhR requires aryl hydrocarbon receptor nuclear translocator (ARNT) to form an active transcription complex and promote the activation of genes which have dioxin responsive element in their regulatory regions. The present study was performed to determine the complete cDNA sequences of porcine AhR and ARNT genes and their chromosomal localization. Total RNA from porcine livers were used to obtain the sequence of the entire porcine transcriptome by next-generation sequencing (NGS;lllumina HiSeq2500). In addition, both, in silico analysis and fluorescence in situ hybridization (FISH) were used to determine chromosomal localization of porcine AhR and ARNT genes. In silico analysis of nucleotide sequences showed that there were two transcript variants of AhR and ARNT genes in the pig. In addition, computer analysis revealed that AhR gene in the pig is located on chromosome 9 and ARNT on chromosome 4. The results of FISH experiment confirmed the localization of porcine AhR and ARNT genes. In the present study, for the first time, the full cDNAs of AhR and ARNT were demonstrated in the pig.In future, it would be interesting to determine the tissue distribution of AhR and ARNT transcript variants in the pig and to test whether these variants are associated with different biological functions and/or different activation pathways.

  9. Disease-tolerance of transgenic tobacco plants expressing Ah-AMP gene of Amaranthus hypochondriacus

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    An antimicrobial peptide gene from Amaranthus hypochondriacus, Ah-AMP, was amplified by PCR and cloned. Sequence analysis results revealed that this gene is 261 bp in length encoding a precursor polypeptide of 87 amino acid residues. Ah-AMP gene was inserted in the binary vector pBin438 to construct a plant expression vector pBinAH916. Leave explants of Nicotiana tabacum var. SR1 were transformed with Agrobacterium tumefaciens LBA4404 harboring the above expression vector. Results from PCR, Southern and Northern blot analyses confirmed that the Ah-AMP gene had been integrated into the tobacco genome and was transcribed at mRNA level. Two bacterial-resistant transgenic plants were selected by inoculating the plants with Pseudomonas solanacearum and statistic analysis of two T1 lines showed that the resistance increased by 2.24 and 1.62 grade and the disease index decreased by 49.6% and 37.3% respectively when compared with the non-transformed control plants SR1. The results from challenging the plants with inoculums of Phytophthora parasitica showed that the symptom development was delayed and disease index was significantly reduced. These results suggest that Ah-AMP gene may be a potentially valuable gene for genetic engineering of plant for disease-resistance.

  10. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

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    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  11. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus)

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    Yang Lihua; Zha Jinmiao; Li Wei; Li Zhaoli [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China); Wang Zijian, E-mail: wangzj@rcees.ac.cn [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China)

    2010-05-05

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333 {mu}g/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na{sup +},K{sup +}-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10 {mu}g/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10 {mu}g/l. The expressions of Na{sup +},K{sup +}-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100 {mu}g/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  12. A novel statistical algorithm for gene expression analysis helps differentiate pregnane X receptor-dependent and independent mechanisms of toxicity.

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    M Ann Mongan

    Full Text Available Genome-wide gene expression profiling has become standard for assessing potential liabilities as well as for elucidating mechanisms of toxicity of drug candidates under development. Analysis of microarray data is often challenging due to the lack of a statistical model that is amenable to biological variation in a small number of samples. Here we present a novel non-parametric algorithm that requires minimal assumptions about the data distribution. Our method for determining differential expression consists of two steps: 1 We apply a nominal threshold on fold change and platform p-value to designate whether a gene is differentially expressed in each treated and control sample relative to the averaged control pool, and 2 We compared the number of samples satisfying criteria in step 1 between the treated and control groups to estimate the statistical significance based on a null distribution established by sample permutations. The method captures group effect without being too sensitive to anomalies as it allows tolerance for potential non-responders in the treatment group and outliers in the control group. Performance and results of this method were compared with the Significant Analysis of Microarrays (SAM method. These two methods were applied to investigate hepatic transcriptional responses of wild-type (PXR(+/+ and pregnane X receptor-knockout (PXR(-/- mice after 96 h exposure to CMP013, an inhibitor of β-secretase (β-site of amyloid precursor protein cleaving enzyme 1 or BACE1. Our results showed that CMP013 led to transcriptional changes in hallmark PXR-regulated genes and induced a cascade of gene expression changes that explained the hepatomegaly observed only in PXR(+/+ animals. Comparison of concordant expression changes between PXR(+/+ and PXR(-/- mice also suggested a PXR-independent association between CMP013 and perturbations to cellular stress, lipid metabolism, and biliary transport.

  13. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

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    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of

  14. Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification.

    Science.gov (United States)

    Son, Bo-Kyung; Akishita, Masahiro; Iijima, Katsuya; Ogawa, Sumito; Maemura, Koji; Yu, Jing; Takeyama, Kenichi; Kato, Shigeaki; Eto, Masato; Ouchi, Yasuyoshi

    2010-03-05

    Recent epidemiological studies have found that androgen deficiency is associated with a higher incidence of cardiovascular disease in men. However, little is known about the mechanism underlying the cardioprotective effects of androgens. Here we show the inhibitory effects of testosterone on vascular calcification and a critical role of androgen receptor (AR)-dependent transactivation of growth arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P(i))-induced calcification of vascular smooth muscle cells (VSMC). Testosterone and nonaromatizable androgen dihydrotestosterone inhibited P(i)-induced calcification of human aortic VSMC in a concentration-dependent manner. Androgen inhibited P(i)-induced VSMC apoptosis, an essential process for VSMC calcification. The effects on VSMC calcification were mediated by restoration of P(i)-induced down-regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation. These effects of androgen were blocked by an AR antagonist, flutamide, but not by an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic role of the AR in Gas6 expression and found an abundant expression of AR predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6 promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this effect was abrogated by flutamide and by AR siRNA. Site-specific mutation revealed that the proximal ARE was essential for androgen-dependent transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6. These results indicate that AR signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens.

  15. Molecular analysis of the chloroplast Cu/Zn-SOD gene (AhCSD2) in peanut

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    Xiurong Zhang; Qian Wan; Fengzhen Liu⁎; Kun Zhang; Aiqing Sun; Bing Luo; Li Sun; Yongshan Wan⁎⁎

    2015-01-01

    Superoxide dismutase (SOD, EC 1.15.1.1) plays a key role in response to drought stress, and differences in SOD activity changes among cultivars are important under drought conditions. We obtained the full-length DNA of the chloroplast Cu/Zn-SOD gene (AhCSD2) from 11 allotetraploid cultivars and 5 diploid wild species in peanut. BLAST search against the peanut genome showed that the AhCSD2 genes gCSD2-1 and gCSD2-2 are located at the tops of chromosome A03 (A genome) and B03 (B genome), respectively, and both contain 8 exons and 7 introns. Nucleotide sequence analyses indicated that gCSD2-2 sequences were identical among all the tested cultivars, while gCSD2-1 sequences showed allelic variations. The amino acid sequences deduced from gCSD2-1 and gCSD2-2 both contain a chloroplast transit peptide and are distinguished by 6 amino acid (aa) residue differences. The other 2 aa residue variations in the mature peptide regions give rise to three-dimensional structure changes of the protein deduced from the genes gCSD2-1 and gCSD2-2. Sequences analyses of cultivars and wild species showed that gCSD2-2 of Arachis hypogaea and gAipCSD2 (Arachis ipaensis) are identical, and despite the abundant polymorphic loci between gCSD2-1 of A. hypogaea and sequences from A genome wild species, the deduced amino acid sequence of AhCSD2-1 (A. hypogaea) is identical to that of AduCSD2 (Arachis duranensis), whereas AcoCSD2 (Arachis correntina) and AcaCSD2 (Arachis cardenasii) both have 2 aa differences in the transit peptide region compared with AhCSD2-1 (A. hypogaea). Based on the Peanut Genome Project, promoter prediction revealed many stress-related cis-acting elements within the potential promoter regions (pp-A and pp-B). pp-A contains more binding sites for drought-associated transcriptional factors than pp-B. We hypothesize that the marked changes in SOD activity in different cultivars under drought stress are tightly regulated by transcription factors through transcription and

  16. Molecular analysis of the chloroplast Cu/Zn-SOD gene(AhCSD2) in peanut

    Institute of Scientific and Technical Information of China (English)

    Xiurong; Zhang; Qian; Wan; Fengzhen; Liu; Kun; Zhang; Aiqing; Sun; Bing; Luo; Li; Sun; Yongshan; Wan

    2015-01-01

    Superoxide dismutase(SOD, EC 1.15.1.1) plays a key role in response to drought stress, and differences in SOD activity changes among cultivars are important under drought conditions. We obtained the full-length DNA of the chloroplast Cu/Zn-SOD gene(Ah CSD2)from 11 allotetraploid cultivars and 5 diploid wild species in peanut. BLAST search against the peanut genome showed that the Ah CSD2 genes g CSD2-1 and g CSD2-2 are located at the tops of chromosome A03(A genome) and B03(B genome), respectively, and both contain 8exons and 7 introns. Nucleotide sequence analyses indicated that g CSD2-2 sequences were identical among all the tested cultivars, while g CSD2-1 sequences showed allelic variations.The amino acid sequences deduced from g CSD2-1 and g CSD2-2 both contain a chloroplast transit peptide and are distinguished by 6 amino acid(aa) residue differences. The other 2aa residue variations in the mature peptide regions give rise to three-dimensional structure changes of the protein deduced from the genes g CSD2-1 and g CSD2-2. Sequences analyses of cultivars and wild species showed that g CSD2-2 of Arachis hypogaea and g Aip CSD2(Arachis ipaensis) are identical, and despite the abundant polymorphic loci between g CSD2-1 of A.hypogaea and sequences from A genome wild species, the deduced amino acid sequence of Ah CSD2-1(A. hypogaea) is identical to that of Adu CSD2(Arachis duranensis), whereas Aco CSD2(Arachis correntina) and Aca CSD2(Arachis cardenasii) both have 2 aa differences in the transit peptide region compared with Ah CSD2-1(A. hypogaea). Based on the Peanut Genome Project, promoter prediction revealed many stress-related cis-acting elements within the potential promoter regions(pp-A and pp-B). pp-A contains more binding sites for drought-associated transcriptional factors than pp-B. We hypothesize that the marked changes in SOD activity in different cultivars under drought stress are tightly regulated by transcription factors through transcription and

  17. Acquisition of Insect-Resistant Transgenic Maize Harboring a Truncated cry1Ah Gene via Agrobacterium-Mediated Transformation

    Institute of Scientific and Technical Information of China (English)

    LI Xiu-ying; LANG Zhi-hong; ZHANG Jie; HE Kang-lai; ZHU Li; HUANG Da-fang

    2014-01-01

    A novel insecticidal gene cry1Ah was cloned from Bacillus thuringiensis isolate BT8 previously for plant genetic engineering improvement. Truncated active Cry1Ah toxin has a toxicity level similar to that of the full-length Cry1Ah toxin. In this study, plant expression vector pMhGM harboring truncated cry1Ah gene was transformed into maize (Zea mays L.) immature embryos by Agrobacterium tumefaciens-mediated transformation at which maize alcohol dehydrogenase matrix attachment regions (madMARs) were incorporated on both sides of the gene expression cassette to improve gene expression. A total of 23 PCR positive events were obtained with a transformation efifciency of 5%around. Bioassay results showed that events 1-4 and 1-5 exhibited enhanced resistance to the Asian corn borer (Ostrinia furnacalis). These two events were further conifrmed by molecular analysis. Southern blot suggested that a single copy of the cry1Ah gene was successfully integrated into the maize genome. Western blot and ELISA showed that the foreign gene cry1Ah was expressed stably at high level in maize and could be inherited stably over generations. The results of a bioassay of T1-T4 transgenic maize plants indicated that the transgenic plants were highly toxic to the Asian corn borer and their resistance could be inherited stably from generation to generation. Thus, events 1-4 and 1-5 are good candidates for the breeding of insect-resistant maize.

  18. The Peanut (Arachis hypogaea L. Gene AhLPAT2 Increases the Lipid Content of Transgenic Arabidopsis Seeds.

    Directory of Open Access Journals (Sweden)

    Silong Chen

    Full Text Available Lysophosphatidic acid acyltransferase (LPAT, which converts lysophosphatidic acid (LPA to phosphatidic acid (PA, catalyzes the addition of fatty acyl moieties to the sn-2 position of the LPA glycerol backbone in triacylglycerol (TAG biosynthesis. We recently reported the cloning and temporal-spatial expression of a peanut (Arachis hypogaea AhLPAT2gene, showing that an increase in AhLPAT2 transcript levels was closely correlated with an increase in seed oil levels. However, the function of the enzyme encoded by the AhLPAT2 gene remains unclear. Here, we report that AhLPAT2 transcript levels were consistently higher in the seeds of a high-oil cultivar than in those of a low-oil cultivar across different seed developmental stages. Seed-specific overexpression of AhLPAT2 in Arabidopsis results in a higher percentage of oil in the seeds and greater-than-average seed weight in the transgenic plants compared with the wild-type plants, leading to a significant increase in total oil yield per plant. The total fatty acid (FA content and the proportion of unsaturated FAs also increased. In the developing siliques of AhLPAT2-overexpressing plants, the expression levels of genes encoding crucial enzymes involved in de novo FA synthesis, acetyl-CoA subunit (AtBCCP2 and acyl carrier protein 1 (AtACP1 were elevated. AhLPAT2 overexpression also promoted the expression of several key genes related to TAG assembly, sucrose metabolism, and glycolysis. These results demonstrate that the expression of AhLPAT2 plays an important role in glycerolipid production in peanuts.

  19. Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

    Science.gov (United States)

    Lee, Andrew C. Y.; Zhu, Houshun; Zhang, Anna J. X.; Li, Can; Wang, Pui; Li, Chuangen; Chen, Honglin; Hung, Ivan F. N.; To, Kelvin K. W.

    2015-01-01

    Influenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections. In this study, we compared serum hemagglutination inhibition (HI) and microneutralization (MN) antibody titers of mice challenged with wild-type A(H7N9) viruses [H7N9(Anhui) and H7N9(Zhejiang)], an A(H1N1)pdm09 virus [pH1N1(2009)], and a recombinant A(H7N9) virus with PR8/H1N1 internal genes (rg-PR8-H7-N9). All mice infected by H7N9(Anhui) and H7N9(Zhejiang) developed serum HI antibodies at 14 days postinfection (dpi) but no detectable MN antibodies, even at 28 dpi. A low level of neutralizing activity was detected in H7N9(Anhui)- and H7N9(Zhejiang)-infected mice using fluorescent focus MN assay, but convalescent-phase serum samples obtained from H7N9(Anhui)-infected mice did not reduce the mortality of naive mice after homologous virus challenge. Reinfection with homologous A(H7N9) virus induced higher HI and MN titers than first infection. In contrast, pH1N1(2009) virus infection induced robust HI and MN antibody responses, even during the first infection. Moreover, rg-PR8-H7-N9 induced significantly higher HI and MN antibody titers than H7N9(Zhejiang). In conclusion, the internal genes of A(H7N9) virus can affect the humoral immune response against homologous viral surface proteins, which may also contribute to the virulence of A(H7N9) virus. PMID:26446420

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xingguo, E-mail: chengx@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Vispute, Saurabh G. [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Cheng, Christine; Kharitonenkov, Alexei [Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, IN 46285 (United States); Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)

    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.

  1. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza

    NARCIS (Netherlands)

    Cheng, Zhongshan; Zhou, Jie; To, Kelvin Kai-Wang; Chu, Hin; Li, Cun; Wang, Dong; Yang, Dong; Zheng, Shufa; Hao, Ke; Bosse, Yohan; Obeidat, Ma'en; Brandsma, Corry-Anke; Song, You-Qiang; Chen, Yu; Zheng, Bo-Jian; Li, Lanjuan; Yuen, Kwok-Yung

    2015-01-01

    The genetic predisposition to severe A(H1N1) 2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expressi

  2. Aryl hydrocarbon receptor (AhR-mediated perturbations in gene expression during early stages of CD4+ T-cell differentiation

    Directory of Open Access Journals (Sweden)

    Diana eRohlman

    2012-08-01

    Full Text Available Activation of the aryl hydrocarbon receptor (AhR by its prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, mediates potent suppression of T-cell dependent immune responses. The suppressive effects of TCDD occur early during CD4+ T-cell differentiation in the absence of effects on proliferation and have recently been associated with the induction of AhR-dependent regulatory T-cells (Treg. Since AhR functions as a ligand-activated transcription factor, changes in gene expression induced by TCDD during the early stages of CD4+ T-cell differentiation are likely to reflect fundamental mechanisms of AhR action. A custom panel of genes associated with T-cell differentiation was used to query changes in gene expression induced by exposure to 1 nM TCDD. CD4+ T-cells from AhR+/+ and AhR-/- mice were cultured with cytokines known to polarize the differentiation of T-cells to various effector lineages. Treatment with TCDD induced expression of Cyp1a1, Cyp1b1 and Ahrr in CD4+ T-cells from AhR+/+ mice under all culture conditions, validating the presence and activation of AhR in these cells. The highest levels of AhR activation occurred under Th17 conditions at 24 hours and Tr1 conditions at 48 hours. Unexpectedly, expression levels of most genes associated with early T-cell differentiation were unaltered by AhR activation, including lineage-specific genes that drive CD4+ T-cell polarization. The major exception was AhR-dependent up-regulation of Il22 that was seen under all culture conditions. Independent of TCDD, AhR down-regulated the expression of Il17a and Rorc based on increased expression of these genes in AhR-deficient cells across culture conditions. These findings are consistent with a role for AhR in down-regulation of inflammatory immune responses and implicate IL-22 as a potential contributor to the immunosuppressive effects of TCDD.

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

    Directory of Open Access Journals (Sweden)

    Matthews Jason

    2011-07-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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 200μg/kg of TCDD died within 20days, 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.

  5. Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

    Science.gov (United States)

    Tsuge, Mitsuru; Oka, Takashi; Yamashita, Nobuko; Saito, Yukie; Fujii, Yosuke; Nagaoka, Yoshiharu; Yashiro, Masato; Tsukahara, Hirokazu; Morishima, Tsuneo

    2014-02-01

    Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

  6. Newly emerging mutations in the matrix genes of the human influenza A(H1N1)pdm09 and A(H3N2) viruses reduce the detection sensitivity of real-time reverse transcription-PCR.

    Science.gov (United States)

    Yang, Ji-Rong; Kuo, Chuan-Yi; Huang, Hsiang-Yi; Wu, Fu-Ting; Huang, Yi-Lung; Cheng, Chieh-Yu; Su, Yu-Ting; Chang, Feng-Yee; Wu, Ho-Sheng; Liu, Ming-Tsan

    2014-01-01

    New variants of the influenza A(H1N1)pdm09 and A(H3N2) viruses were detected in Taiwan between 2012 and 2013. Some of these variants were not detected in clinical specimens using a common real-time reverse transcription-PCR (RT-PCR) assay that targeted the conserved regions of the viral matrix (M) genes. An analysis of the M gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time RT-PCR assay bind; these included three mutations (G225A, T228C, and G238A) in the A(H1N1)pdm09 virus, as well as one mutation (C163T) in the A(H3N2) virus. These accumulated mismatch mutations, together with the previously identified C154T mutation of the A(H1N1)pdm09 virus and the C153T and G189T mutations of the A(H3N2) virus, result in a reduced detection sensitivity for the real-time RT-PCR assay. To overcome the loss of assay sensitivity due to mismatch mutations, we established a real-time RT-PCR assay using degenerate nucleotide bases in both the primers and probe and successfully increased the sensitivity of the assay to detect circulating variants of the human influenza A viruses. Our observations highlight the importance of the simultaneous use of different gene-targeting real-time RT-PCR assays for the clinical diagnosis of influenza.

  7. Retinoic acid receptor-dependent, cell-autonomous, endogenous retinoic acid signaling and its target genes in mouse collecting duct cells.

    Science.gov (United States)

    Wong, Yuen Fei; Wilson, Patricia D; Unwin, Robert J; Norman, Jill T; Arno, Matthew; Hendry, Bruce M; Xu, Qihe

    2012-01-01

    Vitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-trans retinoic acid (tRA), which binds retinoic acid receptors (RARs) to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB) and collecting duct (CD) cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively. To explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three). Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling. A rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.

  8. Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms.

    Science.gov (United States)

    Cai, Demin; Wang, Junjian; Jia, Yimin; Liu, Haoyu; Yuan, Mengjie; Dong, Haibo; Zhao, Ruqian

    2016-01-01

    Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3g/kg) throughout the pregnancy to explore the effects of maternal methyl-donor nutrient on neonatal expression of hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated with down-regulated hepatic expression of lipogenic genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine to s-adenosyl homocysteine ratio was elevated in the liver of betaine-exposed piglets, which was accompanied by DNA hypermethylation on FAS and SCD gene promoters and more enriched repression histone mark H3K27me3 on SCD gene promoter. Furthermore, glucocorticoid receptor (GR) binding to SCD gene promoter was diminished along with reduced serum cortisol and liver GR protein content in betaine-exposed piglets. GR-mediated SCD gene regulation was confirmed in HepG2 cells in vitro. Dexamethasone (Dex) drastically increased the luciferase activity of porcine SCD promoter, while the deletion of GR response element on SCD promoter significantly attenuated Dex-mediated SCD transactivation. In addition, miR-let-7e, miR-1285 and miR-124a, which respectively target porcine SCD, ACC and GR, were significantly up-regulated in the liver of betaine-exposed piglets, being in accordance with decreased protein content of these three genes. Taken together, our results suggest that maternal dietary betaine supplementation during gestation attenuates hepatic lipogenesis in neonatal piglets via epigenetic and GR-mediated mechanisms.

  9. Methoxychlor and triclosan stimulates ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an estrogen receptor-dependent pathway.

    Science.gov (United States)

    Kim, Joo-Young; Yi, Bo-Rim; Go, Ryeo-Eun; Hwang, Kyung-A; Nam, Ki-Hoan; Choi, Kyung-Chul

    2014-05-01

    Methoxychlor and triclosan are emergent or suspected endocrine-disrupting chemicals (EDCs). Methoxychlor [MXC; 1,1,1-trichlor-2,2-bis (4-methoxyphenyl) ethane] is an organochlorine pesticide that has been primarily used since dichlorodiphenyltrichloroethane (DDT) was banned. In addition, triclosan (TCS) is used as a common component of soaps, deodorants, toothpastes, and other hygiene products at concentrations up to 0.3%. In the present study, the potential impact of MXC and TCS on ovarian cancer cell growth and underlying mechanism(s) was examined following their treatments in BG-1 ovarian cancer cells. As results, MXC and TCS induced BG-1 cell growth via regulating cyclin D1, p21 and Bax genes related with cell cycle and apoptosis. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay confirmed that the proliferation of BG-1 ovarian cancer cells was stimulated by MXC (10(-6), 10(-7), 10(-8), and 10(-9)M) or TCS (10(-6), 10(-7), 10(-8), and 10(-9)M). Treatment of BG-1 cells with MXC or TCS resulted in the upregulation of cyclin D1 and downregulation of p21 and Bax transcriptions. In addition, the protein level of cyclin D1 was increased by MXC or TCS while p21 and Bax protein levels appeared to be reduced in these cells. Furthermore, MXC- or TCS-induced alterations of these genes were reversed in the presence of ICI 182,780 (10(-7)M), suggesting that the changes in these gene expressions may be regulated by an ER-dependent signaling pathway. In conclusion, the results of our investigation indicate that two potential EDCs, MXC and TCS, may stimulate ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an ER-dependent pathway.

  10. Ubi1 intron-mediated enhancement of the expression of Bt cry1Ah gene in transgenic maize (Zea mays L.)

    Institute of Scientific and Technical Information of China (English)

    WANG YueBing; LANG Zhihong; ZHANG Jie; HE KangLai; SONG FuPing; HUANG DaFang

    2008-01-01

    The cry1Ah gone was one of novel insecticidal genes cloned from Bacillus thuringiensis isolate BT8. Two plant expression vectors containing cry1Ah gone were constructed. The first intron of maize ubiqutin1 gone was inserted between the maize Ubiquitin promoter and cry1Ah gone in one of the plant expressing vectors (pUUOAH). The two vectors were introduced into maize immature embryonic calli by microprojectile bombardment, and the reproductively plants were acquired. PCR and Southern blot analysis showed that foreign genes had been integrated into maize genome and inherited to the next generation stably. The ELISA assay to T1 and T2 generation plants showed that the expression of Cry1Ah protein in the construct containing the ubi1 intron (pUUOAH) was 20% higher than that of the intronless construct (pUOAH). Bioassay results showed that the transgenic maize harboring cry1Ah gone had high resistance to the Asian corn borers and the insecticidal activity of the transgenic maize containing the ubi1 intron was higher than that of the intronless construct. These results indicated that the maize ubil intron can enhance the expression of the Bt cry1Ah gone in transgenic maize efficiently

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

    Science.gov (United States)

    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.

  12. The novel and taxonomically restricted Ah24 gene from grain amaranth (Amaranthus hypochondriacus has a dual role in development and defense

    Directory of Open Access Journals (Sweden)

    Julio Armando Massange-Sanchez

    2015-08-01

    Full Text Available Grain amaranths tolerate stress and produce highly nutritious seeds. We have identified several (abiotic stress-responsive genes of unknown function in Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed in young or developing tissues; it was also strongly induced by mechanical damage, insect herbivory and methyl jasmonate and in meristems and newly emerging leaves of severely defoliated plants. Interestingly, an in silico analysis of its 1304 bp promoter region showed a predominance of regulatory boxes involved in development, but not in defense. The Ah24 cDNA encodes a predicted cytosolic protein of 164 amino acids, the localization of which was confirmed by confocal microscopy. Additional in silico analysis identified several other Ah24 homologs, present almost exclusively in plants belonging to the Caryophyllales. The possible function of this gene in planta was examined in transgenic Ah24 overexpressing Arabidopsis thaliana and Nicotiana tabacum plants. Transformed Arabidopsis showed enhanced vegetative growth and increased leaf number with no penalty in one fitness component, such as seed yield, in experimental conditions. Transgenic tobacco plants, which grew and reproduced normally, had increased insect herbivory resistance. Modified vegetative growth in transgenic Arabidopsis coincided with significant changes in the expression of genes controlling phytohormone synthesis or signaling, whereas increased resistance to insect herbivory in transgenic tobacco coincided with higher jasmonic acid and proteinase inhibitor activity levels, plus the accumulation of nicotine and several other putative defense-related metabolites. It is proposed that the primary role of the Ah24 gene in A. hypochondriacus is to contribute to a rapid recovery post-wounding or defoliation, although its participation in defense against insect herbivory is also plausible.

  13. The novel and taxonomically restricted Ah24 gene from grain amaranth (Amaranthus hypochondriacus) has a dual role in development and defense

    Science.gov (United States)

    Massange-Sanchez, Julio A.; Palmeros-Suarez, Paola A.; Martinez-Gallardo, Norma A.; Castrillon-Arbelaez, Paula A.; Avilés-Arnaut, Hamlet; Alatorre-Cobos, Fulgencio; Tiessen, Axel; Délano-Frier, John P.

    2015-01-01

    Grain amaranths tolerate stress and produce highly nutritious seeds. We have identified several (a)biotic stress-responsive genes of unknown function in Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed in young or developing tissues; it was also strongly induced by mechanical damage, insect herbivory and methyl jasmonate and in meristems and newly emerging leaves of severely defoliated plants. Interestingly, an in silico analysis of its 1304 bp promoter region showed a predominance of regulatory boxes involved in development, but not in defense. The Ah24 cDNA encodes a predicted cytosolic protein of 164 amino acids, the localization of which was confirmed by confocal microscopy. Additional in silico analysis identified several other Ah24 homologs, present almost exclusively in plants belonging to the Caryophyllales. The possible function of this gene in planta was examined in transgenic Ah24 overexpressing Arabidopsis thaliana and Nicotiana tabacum plants. Transformed Arabidopsis showed enhanced vegetative growth and increased leaf number with no penalty in one fitness component, such as seed yield, in experimental conditions. Transgenic tobacco plants, which grew and reproduced normally, had increased insect herbivory resistance. Modified vegetative growth in transgenic Arabidopsis coincided with significant changes in the expression of genes controlling phytohormone synthesis or signaling, whereas increased resistance to insect herbivory in transgenic tobacco coincided with higher jasmonic acid and proteinase inhibitor activity levels, plus the accumulation of nicotine and several other putative defense-related metabolites. It is proposed that the primary role of the Ah24 gene in A. hypochondriacus is to contribute to a rapid recovery post-wounding or defoliation, although its participation in defense against insect herbivory is also plausible. PMID:26300899

  14. Effect of TBT and PAHs on CYP1A, AhR and Vitellogenin Gene Expression in the Japanese Eel, Anguilla japonica.

    Science.gov (United States)

    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.

  15. 花生AhDRRP基因启动子的克隆%Molecular clonning of promoter sequence of AhDRRP gene from Arachis hypogaea L.

    Institute of Scientific and Technical Information of China (English)

    钟旎; 李万福; 梁炫强

    2011-01-01

    采用基于PCR的基因组DNA步移法,首次从抗黄曲霉品种粤油20花生中克隆AhDRRP基因起始密码子ATG上游403 bp启动子序列,并对其进行植物顺式作用元件数据库PLACE预测分析.研究结果表明,该启动子序列含有大量的TATA box,CAAT box,GATA box; CURECORECR、DOFCOREZM、TAAAGSTKST1等多种抗逆应答元件以及植物激素调节元件2SSEEDPROTBANAPA、ARR1AT、SEF1MOTIF、SEF4MOTIFGM7S等,预示了该基因可能在植物的逆境应答中发挥重要作用.

  16. TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts.

    Science.gov (United States)

    Henry, Ellen C; Welle, Stephen L; Gasiewicz, Thomas A

    2010-03-01

    The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1'H-indolo-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5muM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible.

  17. Search for Ah(dioxin) receptor target genes which mediate dioxin toxicity: induction of p27{sup Kip1} cell cycle inhibitor and N-myristoyltransferase 2

    Energy Technology Data Exchange (ETDEWEB)

    Kolluri, S.K.

    1999-01-01

    Dioxins, in particular TCDD, are potent mammalian toxins acting predominantly in the thymus and skin, in body weight regulation and in liver carcinogenesis. The Ah receptor (AhR) a ligand activated transcription factor belonging to the bHLH-PAS protein family mediates the toxicity of dioxins. Despite the extensive research conducted during the past 20 years, the mechanism by which AhR mediates the toxicity of dioxins is not understood. Known AhR regulated genes mostly code for xenobiotica metabolizing enzymes but the AhR target gene(s) which mediate toxicity are not known. In this study 5L rat hepatoma cells were employed as a model system for dioxin toxicity in which TCDD severely delays cell cycle progression in the G1 phase by an AhR dependent mechanism. An AhR deficient variant subclone of 5L cells, the BP8 cells, are resistant to TCDD. These AhR-deficient cells were used for a mutational analysis of AhR overexpression to test the required properties of AhR to delay cell cycle progression. Both, the receptor`s capacity for sequence specific DNA recognition and the presence of the transcriptional activation domain are necessary to induce the cell cycle delay. This suggests that AhR mediates the TCDD effects on cell cycle by bona fide induction of yet to be identified target genes. Such AhR target genes were searched following two approaches, e.g. based on the biochemical analysis of the cell cycle machinery and by a systematic search for AhR induced genes. Evidence from biochemical analysis of the cell cycle machinery suggested that TCDD might induce cell cycle inhibitor(s). One of the inhibitory proteins, p27{sup Kip1}, is induced by TCDD in 5L cells. Induction of p27{sup Kip1} occurs through the direct induction of Kip1 mRNA by AhR. AhR-dependent activation of Kip1-transcription is a novel mechanism of Kip1 induction which is distinct from the accumulation of Kip1 protein caused by posttranscriptional regulation in all the cases reported so far. Kip1 is the

  18. Effects of 4-nitrophenol on expression of the ER-α and AhR signaling pathway-associated genes in the small intestine of rats.

    Science.gov (United States)

    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.

  19. Enhancement of hypoxia-induced gene expression in fish liver by the aryl hydrocarbon receptor (AhR) ligand, benzo[a]pyrene (BaP).

    Science.gov (United States)

    Yu, Richard Man Kit; Ng, Patrick Kwok Shing; Tan, Tianfeng; Chu, Daniel Ling Ho; Wu, Rudolf Shiu Sun; Kong, Richard Yuen Chong

    2008-11-21

    Fish in polluted coastal habitats commonly suffer simultaneous exposure to both hypoxia and xenobiotics. Although the adaptive molecular responses to each stress have been described, little is known about the interaction between the signaling pathways mediating these responses. Previous studies in mammalian hepatoma cell lines have shown that hypoxia-inducible factor (HIF)- and/or aryl hydrocarbon receptor (AhR)-activated gene expression is suppressed following co-exposure to hypoxia and the hallmark AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, whether similar crosstalk exists in the non-tumor liver tissues of fish and whether other non-TCDD ligands also play the same inhibitory role in this crosstalk remain unknown. Here, the in vivo hepatic mRNA expression profiles of multiple hypoxia- and AhR-responsive genes (later gene expression=mRNA expression of the gene) were examined in the orange-spotted grouper (Epinephelus coioides) upon single and combined exposures to hypoxia and benzo[a]pyrene (BaP). Combined exposure enhanced hypoxia-induced gene expression but did not significantly alter BaP-induced gene expression. Protein carbonyl content was markedly elevated in fish subjected to combined exposure, indicating accumulation of reactive oxygen species (ROS). Application of diethyldithiocarbamate (DDC) to hypoxia-treated grouper liver explants similarly exaggerated hypoxia-induced gene expression as in the combined stress tissues in vivo. These observations suggest that ROS derived from the combined hypoxia and BaP stress have a role in enhancing hypoxia-induced gene expression.

  20. MOLECULAR CLONING AND GUS-AIDED ACTIVITY ASSAYING OF PROMOTER SEQUENCE OF AhNCED1 GENE FROM Arachis hypogaea L.cv.Yueyou 7%粤油7号花生AhNCED1基因启动子克隆及其活性分析

    Institute of Scientific and Technical Information of China (English)

    万小荣; 莫爱琼; 刘帅; 梁建华; 李玲; 余土元; 郑奕雄

    2011-01-01

    AhNCED1是干旱胁迫下花生中调控脱落酸(abscisic acid,ABA)生物合成的关键基因。本文采用基于PCR的基因组DNA步移法,从抗旱性强的粤油7号花生中克隆AhNCED1基因起始密码子ATG上游2392bp启动子序列,构建该启动子驱动报告基因GUS的植物双元表达载体pAhNCED1p∷GUS,转化野生型拟南芥获得AhNCED1p∷GUS转基因植株。通过GUS染色及其酶活性测定分析AhNCED1p∷GUS转基因拟南芥中AhNCED1p启动子的活性。结果表明,AhNCED1p∷GUS转基因拟南芥叶片中AhNCED1p启动子活性最强,脱水胁迫显著增强7 d龄转基因拟南芥幼苗叶片中AhNCED1p启动子活性。300mmol·L-1山梨醇胁迫或100μmol L-1外源ABA处理3 h明显增强25d龄AhNCED1p∷GUS转基因拟南芥中AhNCED1p启动子活性。结果说明,粤油7号花生AhNCED1基因启动子受渗透胁迫和ABA诱导,与生物信息学预测AhNCED1基因启动子序列中存在逆境胁迫和ABA响应元件的结果相一致。%The nine-cis-epoxycarotenoid dioxygenase(NCED) is considered to be a rate-limiting enzyme involved in abscisic acid(ABA) biosynthesis in plants.The AhNCED1 gene was previously characterized from drought-resistant peanut variety,and was confirmed to be the key gene regulating ABA biosynthesis in peanut plants under drought stress.The levels of drought stress-induced AhNCED1 transcript and endogenous ABA in leaves of drought-resistant peanut were significantly higher than those in drought-sensitive peanut variety.The molecular mechanism of the difference in the levels of AhNCED1 gene expression and ABA accumulation between drought-resistant and drought-sensitive peanut varieties in response to drought stress still needs to be elucidated.In present study,a 2392-bp promoter sequence of 5' upstream of initial codon of AhNCED1 gene from drought-resistant Arachis hypogaea L.cv.Yueyou 7 was cloned through a PCR-based genomic DNA walking method.The promoter sequence was analyzed

  1. The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.

    Science.gov (United States)

    Bomfim, I L; Lamb, F; Fink, K; Szakács, A; Silveira, A; Franzén, L; Azhary, V; Maeurer, M; Feltelius, N; Darin, N; Hallböök, T; Arnheim-Dahlström, L; Kockum, I; Olsson, T

    2017-03-01

    The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.

  2. Identification of Influenza A/H7N9 Virus Infection-Related Human Genes Based on Shortest Paths in a Virus-Human Protein Interaction Network

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2014-01-01

    Full Text Available The recently emerging Influenza A/H7N9 virus is reported to be able to infect humans and cause mortality. However, viral and host factors associated with the infection are poorly understood. It is suggested by the “guilt by association” rule that interacting proteins share the same or similar functions and hence may be involved in the same pathway. In this study, we developed a computational method to identify Influenza A/H7N9 virus infection-related human genes based on this rule from the shortest paths in a virus-human protein interaction network. Finally, we screened out the most significant 20 human genes, which could be the potential infection related genes, providing guidelines for further experimental validation. Analysis of the 20 genes showed that they were enriched in protein binding, saccharide or polysaccharide metabolism related pathways and oxidative phosphorylation pathways. We also compared the results with those from human rhinovirus (HRV and respiratory syncytial virus (RSV by the same method. It was indicated that saccharide or polysaccharide metabolism related pathways might be especially associated with the H7N9 infection. These results could shed some light on the understanding of the virus infection mechanism, providing basis for future experimental biology studies and for the development of effective strategies for H7N9 clinical therapies.

  3. Immunotoxicological Evaluation of Corn Genetically Modified with Bacillus thuringiensis Cry1Ah Gene by a 30-Day Feeding Study in BALB/c Mice

    Science.gov (United States)

    Song, Yan; Liang, Chunlai; Wang, Wei; Fang, Jin; Sun, Nana; Jia, Xudong; Li, Ning

    2014-01-01

    This study was to investigate the immunotoxicological potential of corn genetically modified (GM) with Bacillus thuringiensis (Bt) Cry1Ah gene in BALB/c mice. Female BALB/c mice were randomly assigned to one of the four groups: the negative control group, the parental corn group, the GM corn group and the positive control group with 10 mice per group. Mice in the GM corn group and the parental corn group were fed with diets containing 70% corresponding corn for 30 days. Mice in the negative control group and the positive control group were fed with AIN93G diet, administered with saline or 200 mg/kg of cyclophosphamide (CY) via intraperitoneal injection 24 h before the termination of the study, respectively. At the end of the study, the immunotoxicological effects of the GM corn were evaluated through immunopathology parameters including body and organ weights, hematology and clinical chemistry parameters, histological examination, peripheral blood lymphocytes phenotype; humoral immunity including antibody plaque-forming cell, serum immunoglobulin, cytokine and half hemolysis value; cellular immunity such as mitogen-induced splenocyte proliferation, cytotoxic T-lymphocyte reaction, delayed-type hypersensitivity reaction; non-specific immunity including phagocytic activities of phagocytes, natural killer cell activity. A single dose of cyclophosphamide (200 mg/kg bw) was found to have significant adverse effects on immunopathology, cellular immunity, and humoral immunity in mice. The corn genetically modified with Bt Cry1Ah gene is considered consistent with the parental corn in terms of immunopathology, humoral immunity, cellular immunity and non-specific immunity. No adverse immunotoxicological effects of GM corn with Bt Cry1Ah gene were found when feeding mice for 30 days. PMID:24520311

  4. Immunotoxicological evaluation of corn genetically modified with Bacillus thuringiensis Cry1Ah gene by a 30-day feeding study in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Yan Song

    Full Text Available This study was to investigate the immunotoxicological potential of corn genetically modified (GM with Bacillus thuringiensis (Bt Cry1Ah gene in BALB/c mice. Female BALB/c mice were randomly assigned to one of the four groups: the negative control group, the parental corn group, the GM corn group and the positive control group with 10 mice per group. Mice in the GM corn group and the parental corn group were fed with diets containing 70% corresponding corn for 30 days. Mice in the negative control group and the positive control group were fed with AIN93G diet, administered with saline or 200 mg/kg of cyclophosphamide (CY via intraperitoneal injection 24 h before the termination of the study, respectively. At the end of the study, the immunotoxicological effects of the GM corn were evaluated through immunopathology parameters including body and organ weights, hematology and clinical chemistry parameters, histological examination, peripheral blood lymphocytes phenotype; humoral immunity including antibody plaque-forming cell, serum immunoglobulin, cytokine and half hemolysis value; cellular immunity such as mitogen-induced splenocyte proliferation, cytotoxic T-lymphocyte reaction, delayed-type hypersensitivity reaction; non-specific immunity including phagocytic activities of phagocytes, natural killer cell activity. A single dose of cyclophosphamide (200 mg/kg bw was found to have significant adverse effects on immunopathology, cellular immunity, and humoral immunity in mice. The corn genetically modified with Bt Cry1Ah gene is considered consistent with the parental corn in terms of immunopathology, humoral immunity, cellular immunity and non-specific immunity. No adverse immunotoxicological effects of GM corn with Bt Cry1Ah gene were found when feeding mice for 30 days.

  5. 29. LACK OF ASSOCIATION OF AH RECEPTOR GENE POLYMORPHISM WITH SUSCEPTIBILITY TO BLADDER CANCER IN SHANGHAI POPULATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@The diversity in genetic background largely predetermine the individual susceptibility towards health risk related to xenobiotic exposure. The receptors of signal transduction mechanism are involved in the modulation of toxicological outcome of xenobiotics. The survey of distribution of different polymorphic forms of Ah receptor in Chinese population and probing into their possible association with health risk related with xenobiotic exposure will not only contribute to a better understanding of mechanism of imperilment, but also inspire a clue for a further

  6. American Housing Survey (AHS)

    Data.gov (United States)

    Department of Housing and Urban Development — The AHS is the largest, regular national housing sample survey in the United States. The U.S. Census Bureau conducts the AHS to obtain up-to-date housing statistics...

  7. Triple-reassortant influenza A virus with H3 of human seasonal origin, NA of swine origin, and internal A(H1N1) pandemic 2009 genes is established in Danish pigs

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Hjulsager, Charlotte Kristiane; Larsen, Michael Albin

    2017-01-01

    This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been detec...

  8. Triple-reassortant influenza A virus with H3 of human seasonal origin, NA of swine origin, and internal A(H1N1) pandemic 2009 genes is established in Danish pigs

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Hjulsager, Charlotte Kristiane; Larsen, Michael Albin

    2017-01-01

    This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been detec...

  9. Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway.

    Science.gov (United States)

    Lee, Hye-Rim; Hwang, Kyung-A; Park, Min-Ah; Yi, Bo-Rim; Jeung, Eui-Bae; Choi, Kyung-Chul

    2012-05-01

    Various endocrine disrupting chemicals (EDCs) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors (ERs), causing human health problems such as abnormal reproduction and carcinogenesis. In this study, we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells. MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line; these cells are, therefore, a useful in vitro model for detecting estrogenic activity in response to EDCs. We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay. We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate cancer cell growth though ER signaling, we co-treated the cells with agonists (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI 182,780) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes, especially ones affecting the G1/S transition via ERα signaling. These collective results confirm the carcinogenicity of these EDCs in vitro. Further studies are required to determine whether EDCs promote carcinogenesis in vivo.

  10. The crystal structure of the AhRR/ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription.

    Science.gov (United States)

    Sakurai, Shunya; Shimizu, Toshiyuki; Ohto, Umeharu

    2017-09-13

    2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds (TCDDs) are extraordinarily potent environmental toxic pollutants. Most of the TCDD toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription. The control of AhR activation is critical for managing AhR-mediated diseases, but the mechanisms by which AhRR represses AhR activation remain poorly understood, due to the lack of structural information. Here, we determined the structure of the AhRR/ARNT heterodimer by X-ray crystallography, which revealed an asymmetric intertwined domain organization presenting structural features that are both conserved and distinct among bHLH-PAS family members. The structures of AhRR/ARNT and AhR/ARNT were similar in the bHLH-PAS-A region, while the PAS-B of ARNT in the AhRR/ARNT complex exhibited a different domain arrangement in this family reported so far. The structure clearly disclosed that AhRR competitively represses AhR binding to ARNT and target DNA, and further suggested the existence of an AhRR/ARNT-specific repression mechanism. This study provides a structural basis for understanding the mechanism by which AhRR represses AhR-mediated gene transcription. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  11. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Gu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States); Han, Seong-Su [Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Toborek, Michal [Department of Neurosurgery, University of Kentucky, Lexington, KY 40536 (United States); Hennig, Bernhard, E-mail: bhennig@uky.edu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States)

    2012-06-01

    Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We

  12. Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits

    NARCIS (Netherlands)

    Waard, de W.J.; Aarts, J.M.M.J.G.; Peijnenburg, A.A.C.M.; Baykus, H.; Talsma, E.F.; Punt, A.; Kok, de T.M.C.M.; Schooten, van F.J.; Hoogenboom, L.A.P.

    2008-01-01

    Cruciferous vegetables and citrus fruits are reported to possess health-beneficial properties, but also have been shown to contain natural aryl hydrocarbon receptor (AhR) agonists (NAhRAs). Binding to the AhR is widely assumed to activate the main pathway by which dioxins, like 2,3,7,8-tetrachlorodi

  13. The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure - effects in reproductive organs.

    Science.gov (United States)

    Brunnberg, Sara; Andersson, Patrik; Poellinger, Lorenz; Hanberg, Annika

    2011-12-01

    The dioxin/aryl hydrocarbon receptor (AhR) mediates most toxic effects of dioxins. In utero/lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fetal/neonatal development and the developing male reproductive tract are among the most sensitive tissues. TCDD causes antiestrogenic responses in rodent mammary gland and uterus and in human breast cancer cell lines in the presence of estrogen. Also, more recently an estrogen-like effect of TCDD/AhR has been suggested in the absence of estrogen. A transgenic mouse expressing a constitutively active AhR (CA-AhR) was developed as a model mimicking a situation of constant exposure to AhR agonists. Male and female reproductive tissues of CA-AhR mice were characterized for some of the effects commonly seen after dioxin exposure. Sexually mature CA-AhR female mice showed decreased uterus weight, while an uterotrophic assay in immature CA-AhR mice resulted in increased uterus weight. In immature mice, both TCDD-exposure and CA-AhR increased the expression of the estrogen receptor target gene Cathepsin D. When co-treated with 17β-estradiol no increase in Cathepsin D levels occurred in either TCDD-exposed or CA-AhR mice. In sexually mature male CA-AhR mice the weights of testis and ventral prostate were decreased and the epididymal sperm reserve was reduced. The results of the present study are in accordance with previous studies on dioxin-exposed rodents in that an activated AhR (here CA-AhR) leads to antiestrogenic effects in the presence of estrogen, but to estrogenic effects in the absence of estrogen. These results suggest the CA-AhR mouse model as a useful tool for studies of continuous low activity of the AhR from early development, resembling the human exposure situation.

  14. The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus.

    Science.gov (United States)

    Ninan, Ipe; Bath, Kevin G; Dagar, Karishma; Perez-Castro, Rosalia; Plummer, Mark R; Lee, Francis S; Chao, Moses V

    2010-06-30

    The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects episodic memory and affective behaviors. However, the precise role of the BDNF Val66Met polymorphism in hippocampal synaptic transmission and plasticity has not yet been studied. Therefore, we examined synaptic properties in the hippocampal CA3-CA1 synapses of BDNF(Met/Met) mice and matched wild-type mice. Although basal glutamatergic neurotransmission was normal, both young and adult mice showed a significant reduction in NMDA receptor-dependent long-term potentiation. We also found that NMDA receptor-dependent long-term depression was decreased in BDNF(Met/Met) mice. However, mGluR-dependent long-term depression was not affected by the BDNF Val66Met polymorphism. Consistent with the NMDA receptor-dependent synaptic plasticity impairment, we observed a significant decrease in NMDA receptor neurotransmission in the CA1 pyramidal neurons of BDNF(Met/Met) mice. Thus, these results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus.

  15. Association of polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 genes with levels of DNA damage in peripheral blood lymphocytes among coke-oven workers

    Energy Technology Data Exchange (ETDEWEB)

    Yongwen Chen; Yun Bai; Jing Yuan; Weihong Chen; Jianya Sun; Hong Wang; Huashan Liang; Liang Guo; Xiaobo Yang; Hao Tan; Yougong Su; Qingyi Wei; Tangchun Wu [Huazhong University of Science and Technology, Wuhan (China). Institute of Occupational Medicine and Ministry of Education Key Lab of Environment and Health

    2006-09-15

    Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non-coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. It was found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group. Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys{sup 554} variant genotype were higher than those with the AhR Arg{sup 554}/Arg{sup 554} genotype. Similarly, the Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype. However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation.

  16. Receptor-Dependent Coronavirus Infection of Dendritic Cells

    Science.gov (United States)

    Turner, Brian C.; Hemmila, Erin M.; Beauchemin, Nicole; Holmes, Kathryn V.

    2004-01-01

    In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway. PMID:15113927

  17. American Housing Survey (AHS) 2011

    Data.gov (United States)

    Department of Housing and Urban Development — The AHS is the largest, regular national housing sample survey in the United States. The U.S. Census Bureau conducts the AHS to obtain up-to-date housing statistics...

  18. Molecular epidemiology of influenza A(H1N1PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season

    Directory of Open Access Journals (Sweden)

    Katia Corrêa de Oliveira Santos

    Full Text Available ABSTRACT Compared to previous years, seasonal influenza activity commenced early in São Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016. In addition, influenza A(H1N1pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1pdm09 component of the vaccine for the 2016 influenza season.

  19. Newspapers and Newspaper Ink Contain Agonists for the Ah Receptor

    Science.gov (United States)

    Bohonowych, Jessica E. S.; Zhao, Bin; Timme-Laragy, Alicia; Jung, Dawoon; Di Giulio, Richard T.; Denison, Michael S.

    2010-01-01

    Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the AhR signaling pathway. AhR agonist activity was observed for dimethyl sulfoxide (DMSO), ethanol, and water extracts of printed newspaper, unprinted virgin paper, and black printing ink, where activation of luciferase reporter gene expression was transient, suggesting that the AhR active chemical(s) was metabolically labile. DMSO and ethanol extracts also stimulated AhR transformation and DNA binding, and also competed with [3H]TCDD for binding to the AhR. In addition, DMSO extracts of printed newspaper induced cytochrome P450 1A associated 7-ethoxyresorufin-O-deethylase activity in zebrafish embryos in vivo. Although the responsible bioactive chemical(s) remain to be identified, our results demonstrate that newspapers and printing ink contain relatively potent metabolically labile agonists of the AhR. Given the large amount of recycling and reprocessing of newspapers throughout the world, release of these easily extractable AhR agonists into the environment should be examined and their potential effects on aquatic organisms assessed. PMID:18203687

  20. Cloning and Bioinformatic Analysis of AhGDH1 Gene from Arachis hy pogaea L%花生谷氨酸脱氢酶基因 AhGDH1的克隆与生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    陈湘瑜; 徐日荣; 林栩松; 唐兆秀

    2016-01-01

    A glutamate dehydrogenase gene from A rachis hypogaea L .was obtained by using the in silico cloning technique .Its sequence was amplified using primers designed according to the cDNA sequence .The sequencing confirmed and named the gene AhGDH1 with a GenBank accession number of KT933119. Through the bioinformatic analysis ,the composition of amino acid sequence ,basic physical and chemical properties ,subcellular localization , transmembrane region , signal peptide , guide peptide , and secondary and tertiary structures of the protein were studied .The results showed that the length of cDNA of the gene was 1 713 bp ,which included a 1 236 bp open reading frame and encoded 411 amino acids residue .The encoding protein of the AhGDH1 gene consisted of two typical conserved domains .The homology comparison and phylogenetic analysis indicated that the amino acid encoded by AhGDH1 gene in A .hypogaeawas highly homologous with those encoded by GDH1 gene in Cicer arietinum and others . Thus , it was determined that the protein was a glutamate dehydrogenase . The information provided for the expression analysis and function identification of GDH1 gene in A .hypogaea in the future .%运用电子克隆技术获得花生1个谷氨酸脱氢酶基因cDNA序列,同时设计引物以花生cDNA为模板进行扩增,经测序得到证实,命名为 AhGDH1,GenBank登录号:KT933119。采用生物信息学方法,对该基因编码蛋白从氨基酸组成、基本理化性质、亚细胞定位、跨膜结构域、信号肽导肽、二级结构和三级结构等方面进行了预测和分析。结果表明:该基因cDNA序列长度为1713 bp ,包含1个1236 bp开放阅读框,编码411个氨基酸;该编码蛋白含有谷氨酸脱氢酶两个典型的保守结构域。同源比对分析显示,该基因编码的氨基酸序列与鹰嘴豆等植物的谷氨酸脱氢酶基因具有高度的相似性,进一步确定该蛋白为谷氨酸脱氢酶。

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

    Science.gov (United States)

    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.

  2. Molecular Cloning of Sucrose Synthase Gene and Expression Analysis under Drought Stress in Peanut (Arachis hypogaea L.)%花生蔗糖合酶基因AhSuSy的克隆和干旱胁迫表达分析

    Institute of Scientific and Technical Information of China (English)

    何美敬; 刘立峰; 穆国俊; 侯名语; 陈焕英; 崔顺立

    2012-01-01

    Sucrose synthase (SuSy), a key enzyme in sucrose metabolism, plays an important role in both plant growth and development and osmotic adjustment. A cDNA sequence of sucrose synthase gene, designated AhSuSy (GenBank accession number: JF346233), was isolated from peanut using homologous cloning, RACE, and TAIL-PCR. The full-length of AhSuSy cDNA is 2 790 bp, contained an ORF of 2 421 bp, the 5UTR and 3'UTR of 57 bp and 312 bp, respectively. A peptide of 806 amino acid residues was deduced according to the ORF, which showed more than 75% homologous to the corresponding proteins in soybean, Arabidopsis and maize. The AhSuSy was ligated into pET-32a(+) and transformed into E. Coli competent cell. After induced by IPTG, the fusion protein was obtained and its relative molecular weight was 92 kD, which was consistent with the theoretical value. The tissue specific expression analysis by using semi-quantitative RT-PCR assays indicated that AhSuSy was expressed in root, stem and leaf. After treated with 10% PEG, seedlings of peanut were used to determine transcript level for AhSuSy, sucrose synthase activity and sucrose content. The result showed that all of the three parameters were gradually increased during 4h to 12 h after treatment and the correlation coefficient between sucrose synthase activity and sucrose content was 0.993 (P=0.007<0.01) during this period, then declined from 12 h to 24 h after treatment, which indicated that AhSuSy may play a key role in adaptation of plants to drought stress.%蔗糖合酶(sucrose synthase,SuSy)是蔗糖代谢途径中的关键酶,在植物生长、发育和渗透调节过程中起着重要的作用.本研究利用同源克隆、RACE和TAIL-PCR相结合的方法从花生叶片中分离了蔗糖合酶基因,命名为AhSuSy (GenBank登录号为JF346233).该基因cDNA序列全长2 790 bp,包含一个2 421 bp的开放阅读框(ORF),5’端非编码区57 bp,3’端非编码区为312 bp.根据编码区预测AhSuSy编码806个氨基酸,

  3. Insect-Resistant and Glyphosate-Tolerant Transgenic Maize Transformed by Bt cry1Ah and 2mG2-epsps Genes%转Bt cry1Ah/2mG2-epsps双价基因抗虫/耐除草剂玉米研究

    Institute of Scientific and Technical Information of China (English)

    赫福霞; 郎志宏; 张杰; 陆伟; 何康来; 黄大昉

    2012-01-01

    构建了含有Bt杀虫基因cry1Ah和耐草甘膦基因2mG2-epsps的双价植物表达载体pMAGUHM,通过基因枪轰击Q31×Z31杂交组合的胚性愈伤组织,以2mG2-epsps为筛选标记,通过1 mmo1/L草甘膦异丙胺盐筛选,获得TO代转化植株80株,其中PCR检测有36株为阳性植株,阳性率达45%.对得到的阳性植株的T1、T2代进行了跟踪检测,证明外源基因已整合到玉米基因组中并正确表达.草甘膦及玉米螟抗性检测结果表明,有5个转基因品系表现出具有耐草甘膦和抗虫的双重特性.%A bivalent plant expression vector pMAGUHM expressing the modified Bt cry 1 Ah gene and giyphosate-tolerant 2mG2-epsps gene was constructed and transformed into Zea mays L. calli Q31 ×Z31 hybrid by microprejec-tile bombardment. Using the 2mG2-epspsgene as a selective marker,eighty glyphosate-tolerant maize plantlets were selected by 1 mmol/L glyphosate- isopropylammonium, and thirty-six glyphosate-tolerant maize plantlets were confirmed transgenic plants by PCR analysis. The positive rate was 45%. Further analysis was performed on the Tl and T2 generation and it was confirmed that Bt cry 1 Ah gene and 2mG2-epsps gene had been integrated into the maize genome and expressed successfully.The bioassay of corn borer (Pyramid nubilalis Hubern) resistance and glypho-sate tolerance indicated that five transgenic lines showed both glyphosate tolerant and insect resistant traits.

  4. Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China.

    Science.gov (United States)

    Han, Yan; Sun, Nan; Lv, Qiu-Yue; Liu, Dan-Hong; Liu, Da-Peng

    2016-10-01

    The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups.

  5. Novel avian influenza A(H7N9) virus in tree sparrow, Shanghai, China, 2013.

    Science.gov (United States)

    Zhao, Baihui; Zhang, Xi; Zhu, Wenfei; Teng, Zheng; Yu, Xuelian; Gao, Ye; Wu, Di; Pei, Enle; Yuan, Zhengan; Yang, Lei; Wang, Dayan; Shu, Yuelong; Wu, Fan

    2014-05-01

    In spring 2013, influenza A(H7N9) virus was isolated from an apparently healthy tree sparrow in Chongming Dongping National Forest Park, Shanghai City, China. The entire gene constellation of the virus is similar to that of isolates from humans, highlighting the need to monitor influenza A(H7N9) viruses in different species.

  6. Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus.

    Science.gov (United States)

    Su, Wen; Wang, Chengmin; Luo, Jing; Zhao, Yuliang; Wu, Yan; Chen, Lin; Zhao, Na; Li, Meng; Xing, Chao; Liu, Huimin; Zhang, Hong; Chang, Yung-fu; Li, Tianxian; Ding, Hua; Wan, Xiufeng; He, Hongxuan

    2015-09-22

    Since 2013, avian influenza A(H7N9) viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially H9N2, in Chinese poultry. Despite concerns about the pandemic threat posed by H7N9 viruses, little is known about the biological properties of H7N9 viruses that may recruit internal genes from genetically distinct H9N2 viruses circulating among wild birds. Here, we generated 63 H7N9 reassortants derived from an avian H7N9 and a wild-bird-origin H9N2 virus. Compared with the wild-type parent, 25/63 reassortants had increased pathogenicity in mice. A reassortant containing PB1 of the H9N2 virus was highly lethal to mice and chickens but was not transmissible to guinea pigs by airborne routes; however, three substitutions associated with adaptation to mammals conferred airborne transmission to the virus. The emergence of the H7N9-pandemic reassortant virus highlights that continuous monitoring of H7N9 viruses is needed, especially at the domestic poultry/wild bird interface.

  7. Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus

    Directory of Open Access Journals (Sweden)

    Wen Su

    2015-09-01

    Full Text Available Since 2013, avian influenza A(H7N9 viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially H9N2, in Chinese poultry. Despite concerns about the pandemic threat posed by H7N9 viruses, little is known about the biological properties of H7N9 viruses that may recruit internal genes from genetically distinct H9N2 viruses circulating among wild birds. Here, we generated 63 H7N9 reassortants derived from an avian H7N9 and a wild-bird-origin H9N2 virus. Compared with the wild-type parent, 25/63 reassortants had increased pathogenicity in mice. A reassortant containing PB1 of the H9N2 virus was highly lethal to mice and chickens but was not transmissible to guinea pigs by airborne routes; however, three substitutions associated with adaptation to mammals conferred airborne transmission to the virus. The emergence of the H7N9-pandemic reassortant virus highlights that continuous monitoring of H7N9 viruses is needed, especially at the domestic poultry/wild bird interface.

  8. Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A(H3N2) strains in Korea

    Science.gov (United States)

    Park, Sehee; Bae, Joon-Yong; Yoo, Kirim; Cheong, Hee Jin; Noh, Ji Yun; Hong, Kyung Wook; Lemey, Philippe; Vrancken, Bram; Kim, Juwon; Nam, Misun; Yun, Soo-Hyeon; Cho, Woo In; Song, Joon Young; Kim, Woo Joo; Park, Mee Sook; Song, Jin-Won; Kee, Sun-Ho; Song, Ki-Joon; Park, Man-Seong

    2017-01-01

    Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness. PMID:28257427

  9. Spt10 and Swi4 Control the Timing of Histone H2A/H2B Gene Activation in Budding Yeast ▿

    OpenAIRE

    Eriksson, Peter R.; Ganguli, Dwaipayan; Clark, David J.

    2010-01-01

    The expression of the histone genes is regulated during the cell cycle to provide histones for nucleosome assembly during DNA replication. In budding yeast, histones H2A and H2B are expressed from divergent promoters at the HTA1-HTB1 and HTA2-HTB2 loci. Here, we show that the major activator of HTA1-HTB1 is Spt10, a sequence-specific DNA binding protein with a putative histone acetyltransferase (HAT) domain. Spt10 binds to two pairs of upstream activation sequence (UAS) elements in the HTA1-H...

  10. AhR-mediated and antiestrogenic activity of humic substances.

    Science.gov (United States)

    Janosek, J; Bittner, M; Hilscherová, K; Bláha, L; Giesy, J P; Holoubek, I

    2007-04-01

    Humic substances (HS) were for decades regarded as inert in the ecosystems with respect to their possible toxicity. However, HS have been recently shown to elicit various adverse effects generally attributed to xenobiotics. In our study, we used MVLN and H4IIE-luc cell lines stably transfected with luciferase gene under control of estrogen receptor (ER) and Ah receptor (AhR; receptor connected with so-called dioxin-like toxicity) for assessment of anti/estrogenic and AhR-mediated effects of 12 commercially available humic substances. Out of those, five humic acids were shown to induce AhR-mediated activity with relative potencies related to TCDD 2.6 x 10(-8)-7.4 x 10(-8). Organic extracts of HS solutions also elicited high activities what means that lipophilic molecules are responsible for a great part of effect. However, relatively high activity remaining in extracted solution suggests also presence of polar AhR-agonists. Contribution of persistent organic compounds to the observed effects was ruled out by H(2)SO(4) treatment. Eight out of twelve HS elicited significant antiestrogenic effects with IC(50) ranging from 40 to 164 mg l(-1). The possible explanations of the antiestrogenic effect include sorption of 17-beta-estradiol (E2) on HS, changes in membrane permeability for E2 or another specific mechanism.

  11. Assessing Antigenic Drift of Seasonal Influenza A(H3N2) and A(H1N1)pdm09 Viruses.

    Science.gov (United States)

    Tewawong, Nipaporn; Prachayangprecha, Slinporn; Vichiwattana, Preeyaporn; Korkong, Sumeth; Klinfueng, Sirapa; Vongpunsawad, Sompong; Thongmee, Thanunrat; Theamboonlers, Apiradee; Poovorawan, Yong

    2015-01-01

    Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2) and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens and calculated the perfect-match vaccine efficacy using the pepitope model, which quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1, 3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014 seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant epitope mutations at epitopes B and E. Finally, the vaccine efficacy for A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These findings further confirmed the accelerating antigenic drift of the circulating influenza A(H3N2) in recent years.

  12. AH-64E Apache Remanufacture (AH-64E Remanufacture)

    Science.gov (United States)

    2015-12-01

    strike, armed reconnaissance, Manned-Unmanned Teaming, security and vertical maneuver missions across the full spectrum of warfare from Stability and...Jan 2008 LUT Nov 2009 Nov 2009 May 2010 Nov 2009 Milestone C Jul 2010 Jul 2010 Jan 2011 Sep 2010 IOT &E Mar 2012 Mar 2012 Sep 2012 Mar 2012 FRP Jul...Acronyms and Abbreviations IOT &E - Initial Operational Test and Evaluation LUT - Limited User Test AH-64E Remanufacture December 2015 SAR March 21, 2016

  13. Simulation studies for wells AH-4bis/AH-17 and AH-18, Ahuachapan Geothermal Field

    Energy Technology Data Exchange (ETDEWEB)

    Monterrosa, Manuel Ernesto

    1996-01-24

    Well AH-4bis, at the Ahuachapan Geothermal Field is planned to be drilled on the same pad as the former AH-4. A simulation study was carried out for two casing dameters 13 5/8 and 9 5/8” in order to estimate its production and to know its economic feasibility. The simulation results indcate a high probability of production in the range of 7 Mwe, equivalent to 120 kg/s total mass flow rate, 1250 kJ/kg at 6 bar-a for the new well AH-4bis. Well AH- 17 is good producer, during 1991 after ten years of production, the well was shut-in due to silica scaling problems. A wellbore simulation was carried out in order to predict the new production conditions after the work-over, mainly to estimate the water flow rate in order to reduce the silica scaling. The results indicate a very low water flow rate. The match between the simulated and measured production curves after the work-over was successful. The well AH-18 is located at the southern part of the actual bore field. CEL is planning to expand the borefield at this area and it is neccessary to estimate the possible production condtions at that zone. The results indicate a high probabilty of production at that area. The power potential is estimated at 3.5 Mwe per well at WHP 6 bar-a and the wells will not require induction.

  14. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    Directory of Open Access Journals (Sweden)

    Jacob Aude

    2011-08-01

    Full Text Available Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP or Δ9-tetrahydrocannabinol (Δ9-THC. Results After ex vivo exposure to TCDD (a highly potent AhR ligand for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold and Cyp1b1 protein (2-fold in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

  15. Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

    Science.gov (United States)

    Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

    2015-01-01

    Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF

  16. Casein kinase 1-epsilon deletion increases mu opioid receptor-dependent behaviors and binge eating1.

    Science.gov (United States)

    Goldberg, L R; Kirkpatrick, S L; Yazdani, N; Luttik, K P; Lacki, O A; Keith Babbs, R; Jenkins, D F; Evan Johnson, W; Bryant, C D

    2017-09-01

    Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0.2 mg/kg i.p.) as well as enhanced sensitivity to low-dose fentanyl reward (0.05 mg/kg). Interestingly, female knockout mice also showed a markedly greater escalation in consumption of sweetened palatable food - a behavioral pattern consistent with binge eating that also depends on mu opioid receptor activation. No difference was observed in fentanyl analgesia in the 52.5°C hot plate assay (0-0.4 mg/kg), naloxone conditioned place aversion (4 mg/kg), or methamphetamine conditioned place preference (0-4 mg/kg). To identify molecular adaptations associated with increased drug and food behaviors in knockout mice, we completed transcriptome analysis via mRNA sequencing of the striatum. Enrichment analysis identified terms associated with myelination and axon guidance and pathway analysis identified a differentially expressed gene set predicted to be regulated by the Wnt signaling transcription factor, Tcf7l2. To summarize, Csnk1e deletion increased mu opioid receptor-dependent behaviors, supporting previous studies indicating an endogenous negative regulatory role of Csnk1e in opioid behavior. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  17. Identification and analysis of novel flavonoid agonists and antagonists for the AH and estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, B.; Nagy, S.; Rogers, J.; Denison, M. [Dept. of Environmental Toxicology, Univ. of California, Davis (United States); Nantz, M.; Kurth, M.; Springsteel, M. [Dept. of Chemistry, Univ. of California, Davis (United States)

    2004-09-15

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biological and toxicological effects in a diverse range of species, tissues, and cell types. The most studied effect is induction of gene expression, and, the majority of AhR responsive genes, such as cytochrome P4501A1 (CYP1A1), utilize AhR dependent mechanism of action. While halogenated aromatic hydrocarbons (HAHs) and polycyclic aromatic hydrocarbons (PAHs) are the prototypical ligands of the Ah receptor, it has recently identified that the AhR is activated by a structurally diverse array of hydrophobic natural and synthetic chemicals. Given the structural diversity in AhR ligands, the physiochemical characteristics for high and low affinity ligands seems to be established. Environmental contaminants that can disrupt the endocrine homeostasis of an organism have also gained widespread attention in recent years and numerous chemicals have been identified as having either hormone or anti-hormone properties. However, like the AhR, the structural diversity and characteristics of endocrine disrupters that exert their action via nuclear receptors also seems to be depended on the estrogen receptor (ER). The flavonoids are a diverse family of chemicals commonly found in fruits and vegetables. Members of this family exert cytostatic, apoptotic, anti-inflammatory and anti-angiogenic activities. In addition, several flavonoids are potent modulators of both the expression and activities of specific cytochrome P450 genes/proteins and somel others have estrogenic and antiestrogenic activity. Accordingly flavonoids have attracted attention as possible chemoprotective or chemotherapeutic agents. We have previously developed and analyzed a novel chemical library of flavonoids which contained {proportional_to}200 compounds. The ability of these compounds to activate and/or inhibit AhR- and ER- dependent gene expression was examined by using our recently developed AhR- and ER

  18. Activation of arylhydrocarbon receptor (AhR) in T lineage cells inhibits cellular growth

    Energy Technology Data Exchange (ETDEWEB)

    Nohara, K.; Tomohiro, I.; Chiharu, T. [National Institute for Environmental Studies, Tsukuba (Japan)

    2004-09-15

    Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), exert their toxic effects by binding and activating the arylhydrocarbon receptor (AhR), a liganddependent transcription factor. Upon binding dioxins, the AhR in the cytoplasm is activated and translocated to the nucleus, where it heterodimerizes with another transcription factor, ARNT. The AhR/ARNT heterodimer modulates expressions of various genes by binding xenobiotic responsive elements (XREs) in their enhancer regions or modifies cellular functions through protein-protein interactions. The AhR activation by TCDD exposure induces various immunotoxic reactions including thymus involution and suppression of T cell-dependent antibody production. We have investigated the roles of AhR activation in T lineage cells and their underlying mechanisms by generating transgenic (Tg) mice expressing a constitutively active AhR (CA-AhR) mutant specifically in T cells and by transiently expressing the CA-AhR mutant in Jurkat T cells.

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

    Science.gov (United States)

    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.

  20. Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

    OpenAIRE

    2016-01-01

    ABSTRACT Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H...

  1. Peran Dokter sebagai Saksi Ahli Di Persidangan

    Directory of Open Access Journals (Sweden)

    Rika Susanti

    2013-05-01

    Full Text Available AbstrakPemanfaatan ilmu kedokteran forensik dalam penegakan hukum serta keadilan membutuhkan dokter sebagai saksi ahli medis di persidangan. Saksi ahli pada dasarnya adalah seseorang yang memiliki pengetahuan, pengalaman dan keahlian khusus sebagai dasar dalam memberikan keterangan ahli suatu perkara pidana. Kewajiban dokter untuk membuat keterangan ahli diatur dalam Kitab Undang-undang Acara Pidana dan dalam etika kedokteran. Kehadiran dokter sebagai saksi ahli dapat diminta oleh jaksa penuntut ataupun penasehat hukum tersangka atas persetujuan hakim. Dokter dapat menjadi saksi fakta (dokter yang merawat atau saksi pendapat (ahli independen tergantung keterangan yang dibutuhkan pengadilan. Dalam memberikan keterangan ahli, dokter harus mengikuti ketentuan yang berlaku di persidangan Indonesia, sehingga penting bagi dokter untuk mengetahui tata cara dan sikap dokter sebagai saksi ahli dan mengikuti pedoman menjadi saksi ahli kedokteran.Kata kunci: Dokter sebagai aksi ahli, dasar hukum, persidangan, pedoman saksi ahliAbstractThe utilization of forensic medical science in law enforcement and justice requires a medical doctor as an expert medical witness in court. An expert witness is basically a person who has knowledge, experience and special skill as a basis in providing expertise which is caused a criminal. The obligation of the doctor to make expert explanation is arranged in the book of the law in the crime and in medical ethics.The presence of the doctor as an expert witness can be requested by the prosecutor or the lawyer of the suspect upon approval the judge. Doctors can be as a witness of fact (the treating doctor or as a witness of opinion (the independent expert witness, depending on the information needed at the court. In providing expert information, the doctor should follow the applicable provisions in Council of Indonesia, so it is important for the doctor to know the ordinances and the attitude of doctors acting as medical

  2. 一株对鳞翅目害虫高毒力的苏云金芽孢杆菌菌株基因型鉴定及新基因cry2Ah3克隆%Identification of a Bacillus thuringiensis Strain Highly Toxic to Lepidoptera and Clone of a New Gene cry2Ah3

    Institute of Scientific and Technical Information of China (English)

    董明; 杜立新; 王容燕; 王金耀; 曹伟平; 宋健; 冯书亮

    2010-01-01

    HYW-8是本实验室自行分离的一株对鳞翅目害虫具有高毒力的苏云金芽孢杆菌,PCR-RFLP鉴定含有cry1Ab、cry1E基因和一种新的cry2A基因,根据cry2A全长基因序列设计特异引物,获得全长基因.测序结果表明,该基因开放阅读框为1 896 bp,编码632个氨基酸,相对分子质量(M)是70.774×103,等电点pI=7.79,与已知的cry2Ah2基因编码的蛋白的同源性最高为98%.该基因序列已在GenBank中登记注册,登录号为GU073380,并被国际Bt杀虫晶体蛋白基因命名委员会正式命名为cry2Ah3.SDS-PAGE分析,HYW-8菌株表达130×103大小蛋白,未见70×103大小蛋白.

  3. Over-expression of AhR (aryl hydrocarbon receptor induces neural differentiation of Neuro2a cells: neurotoxicology study

    Directory of Open Access Journals (Sweden)

    Ishihara-Sugano Mitsuko

    2006-09-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption in human and experimental animal offspring following perinatal exposure during development and growth. The molecular mechanism(s of the actions in the brain, however, have not been fully investigated. A major participant in the process of the dioxin-toxicity is the dioxin receptor, namely the aryl hydrocarbon receptor (AhR. AhR regulates the transcription of diverse genes through binding to the xenobiotic-responsive element (XRE. Since the AhR has also been detected in various regions of the brain, the AhR may play a key role in the developmental neurotoxicity of dioxins. This study focused on the effect of AhR activation in the developing neuron. Methods The influence of the AhR on the developing neuron was assessed using the Neuro2a-AhR transfectant. The undifferentiated murine neuroblastoma Neuro2a cell line (ATCC was stably transfected with AhR cDNA and the established cell line was named N2a-Rα. The activation of exogenous AhR in N2a-Rα cells was confirmed using RNAi, with si-AhR suppressing the expression of exogenous AhR. The neurological properties of N2a-Rα based on AhR activation were evaluated by immunohistochemical analysis of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH. Results N2a-Rα cells exhibited constant activation of the exogenous AhR. CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of ligand to the culture medium. N2a-Rα cells exhibited two significant functional features. Morphologically, N2a-Rα cells bore spontaneous neurites exhibiting axon-like properties with the localization of NF-H. In addition, cdc42 expression was increased in comparison to the control cell line. The other is the catecholaminergic neuron-like property. N2a-Rα cells expressed tyrosine hydroxylase (TH mRNA as a

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

    OpenAIRE

    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 i...

  5. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; Eijkeren JCH van; LBO

    1997-01-01

    The interspecies extrapolation of chemical toxicity is traditionally based on the daily administered dose of the chemical. However, in the case of compounds with strong bioaccumulating properties, such as 2,3,7,8-TetraChloroDibenzo-p-Dioxin (TCDD), chronic toxicity is expected to scale better with t

  6. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1997-01-01

    De extrapolatie van de toxiciteit van chemische stoffen van proefdieren naar de mens vindt traditioneel plaats op basis van de dagelijks toegediende hoeveelheid van een stof. Echter, voor stoffen met sterk accumulerende eigenschappen zoals 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) ligt een extrap

  7. AhR transcriptional activity in serum of Inuits across Greenlandic districts

    Directory of Open Access Journals (Sweden)

    Bonefeld-Jorgensen Eva C

    2007-10-01

    Full Text Available Abstract Background Human exposure to lipophilic persistent organic pollutants (POPs including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs, polychlorinated biphenyls (PCBs and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR. The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors. Methods The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast, Qaanaaq (North Coast and Tasiilaq (East Coast. The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors. Results In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food. Conclusion i We observed that the proportion of dioxin like (DL compounds in the

  8. Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease.

    Directory of Open Access Journals (Sweden)

    Sumit Punj

    Full Text Available 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.

  9. Cloning and Characterization of the Arogenate Dehydrogenase Gene from Arachis hypogaca L.%花生预苯胺酸脱氢酶基因AhADH的克隆及分子特性分析

    Institute of Scientific and Technical Information of China (English)

    张福婷; 周双彪; 张冲; 陈华; 蔡铁城; 庄伟建

    2014-01-01

    The full-length cDNA encoding ADH was isolated by modified rapid amplification of cDNA ends (RACE) in peanut (Arachis hypogaca). The cDNA, designated as AhADH, was 1 155 base pairs (bp) long containing an open reading frame ( ORF ) of 810 bp encoding a protein of 269 amino acids . The bioinformatics approach prediction showed that AhADH with a predicted molecular weight of 30.65 kD and the theoretical isoelectric point (PI) of 6.07. The secondary structure was mainly composed of helix and random crimps. Alignments of A. hypogaca ADH amino acid sequences revealed high homologies with other plant ADH, and contained prephenate/arogenate dehydrogenase domain. Real-time fluorescent quantitative PCR (qRT-PCR) analysis revealed that AhADH was preferentially expressed in stem compared with other tissues.%通过改良的RACE技术从花生中分离并克隆出ADH全长cDNA序列,并命名为AhADH,其全长为1155 bp,含一个编码269个氨基酸,长度为810 bp的开放阅读框。生物信息学分析显示AhADH蛋白的分子质量是30.65 kD,理论等电点是6.07,二级结构主要由α-螺旋和无规卷曲组成。序列比对表明花生ADH氨基酸序列含预苯酸/预苯胺酸脱氢酶结构域,且与多种其他植物的ADH具有高度同源性。qRT-PCR分析表明该基因具有组织表达差异性,且在茎中表达量最高。

  10. Anti-Restriction Protein, KlcAHS, Promotes Dissemination of Carbapenem Resistance

    Directory of Open Access Journals (Sweden)

    Xiaofei Jiang

    2017-05-01

    Full Text Available Carbapenemase-producing Klebsiella pneumoniae (KPC has emerged and spread throughout the world. A retrospective analysis was performed on carbapenem-resistant K. pneumoniae isolated at our teaching hospital during the period 2009–2010, when the initial outbreak occurred. To determine the mechanism(s that underlies the increased infectivity exhibited by KPC, Multilocus Sequence Typing (MLST was conducted. A series of plasmids was also extracted, sequenced and analyzed. Concurrently, the complete sequences of blaKPC−2-harboring plasmids deposited in GenBank were summarized and aligned. The blaKPC−2 and KlcAHS genes in the carbapenem-resistant K. pneumoniae isolates were examined. E. coli strains, carrying different Type I Restriction and Modification (RM systems, were selected to study the interaction between RM systems, anti-RM systems and horizontal gene transfer (HGT. The ST11 clone predominated among 102 carbapenem-resistant K. pneumoniae isolates, all harbored the blaKPC−2 gene; 98% contained the KlcAHS gene. KlcAHS was one of the core genes in the backbone region of most blaKPC−2 carrying plasmids. Type I RM systems in the host bacteria reduced the rate of pHS10842 plasmid transformation by 30- to 40-fold. Presence of the anti-restriction protein, KlcAHS, on the other hand, increased transformation efficiency by 3- to 6-fold. These results indicate that RM systems can significantly restrict HGT. In contrast, KlcAHS can disrupt the RM systems and promote HGT by transformation. These findings suggest that the anti-restriction protein, KlcAHS, represents a novel mechanism that facilitates the increased transfer of blaKPC-2 and KlcAHS-carrying plasmids among K. pneumoniae strains.

  11. Aminoflavone, a ligand of the Aryl Hydrocarbon Receptor (AhR), inhibits HIF-1α expression in an AhR-independent fashion

    Science.gov (United States)

    Terzuoli, Erika; Puppo, Maura; Rapisarda, Annamaria; Uranchimeg, Badarch; Cao, Liang; Burger, Angelika M.; Ziche, Marina; Melillo, Giovanni

    2010-01-01

    Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1β/ARNT, which is shared with HIF-1α, a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacological activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1α transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1α by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1α expression in AhR100 cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1α in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1α mRNA expression by approximately 50%. Notably, actinomycin-D completely abrogated the ability of AF to down-regulate HIF-1α mRNA, indicating that active transcription was required for the inhibition of HIF-1α expression. Finally, AF inhibited HIF-1α protein accumulation and the expression of HIF-1-target genes in MCF-7 xenografts. These results demonstrate that AF inhibits HIF-1α in an AhR-independent fashion and they unveil additional activities of AF that may be relevant for its further clinical development. PMID:20736373

  12. Screening of Bacillus thuringiensis Strains with High Toxicity against Spodoptera exigua and Identification of a New cry2Ah5 Gene%对甜菜夜蛾高杀虫毒力苏云金杆菌菌株的筛选及cry2Ah5的克隆表达

    Institute of Scientific and Technical Information of China (English)

    张雅昆; 赵丹; 郭巍; 王伟; 陆秀君; 李瑞军

    2016-01-01

    利用生物活性测定方法从本实验室已分离保存的Bt菌株中筛选出了5株对甜菜夜蛾具有较高杀虫毒力的菌株.该5株Bt菌株对甜菜夜蛾初孵幼虫的LC50值为0.556 ~ 0.914 mg/mL胞晶混合物,其中GS3菌株杀虫活性最高,LC50值为0.556 mg/mL胞晶混合物;包含晶体形态主要是球形、大菱形、小菱形等;所含基因类型主要是cry1Aa、cry1Ab、cry La、cry1Ia、cry1Ib、cry2Ab、cry2Ad、cry2Ah、cry7Ab、cry9Ba等;5株菌株均表达约60 kD和130~150 kD蛋白,其中2株还表达较弱的80 kD蛋白.从GS3菌株中克隆得到一种新的cry2A基因,GenBank登录号为KT692984,由Bt基因国际命名委员会命名为cry2Ah5.该基因开放阅读框为1899 bp,编码632个氨基酸,编码蛋白分子量为70.8 kD,等电点pI为8.18,与其他Cry2Ah蛋白序列相似性为97%~99%.该基因在大肠杆菌BL21(DE3)中表达约70 kD蛋白,与预测分子量相符.本研究筛选得到5株对甜菜夜蛾具有较高杀虫毒力的Bt菌株,克隆表达了一种新的cry2A基因cry2Ah5,为甜菜夜蛾的生物防治提供了新的菌株及基因资源.

  13. Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, Emelia [Department of Medicine, McGill University, Montreal, Quebec (Canada); Zago, Michela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Sarill, Miles [Department of Medicine, McGill University, Montreal, Quebec (Canada); Rico de Souza, Angela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Gomez, Alvin; Matthews, Jason [Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON (Canada); Hamid, Qutayba; Eidelman, David H. [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Baglole, Carolyn J., E-mail: Carolyn.baglole@McGill.ca [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada)

    2014-11-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR{sup −/−}) and wild-type (AhR{sup +/+}) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR{sup −/−} cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR{sup −/−} compared to AhR{sup +/+} cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR{sup +/+} fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR{sup +/+} lung fibroblasts in response to serum, corresponding to a decrease in p27{sup KIP1} protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27{sup KIP1} in AhR{sup −/−} fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the

  14. Methamphetamine induces dopamine D1 receptor-dependent endoplasmic reticulum stress-related molecular events in the rat striatum.

    Directory of Open Access Journals (Sweden)

    Subramaniam Jayanthi

    Full Text Available Methamphetamine (METH is an illicit toxic psychostimulant which is widely abused. Its toxic effects depend on the release of excessive levels of dopamine (DA that activates striatal DA receptors. Inhibition of DA-mediated neurotransmission by the DA D1 receptor antagonist, SCH23390, protects against METH-induced neuronal apoptosis. The initial purpose of the present study was to investigate, using microarray analyses, the influence of SCH23390 on transcriptional responses in the rat striatum caused by a single METH injection at 2 and 4 hours after drug administration. We identified 545 out of a total of 22,227 genes as METH-responsive. These include genes which are involved in apoptotic pathways, endoplasmic reticulum (ER stress, and in transcription regulation, among others. Of these, a total of 172 genes showed SCH23390-induced inhibition of METH-mediated changes. Among these SCH23390-responsive genes were several genes that are regulated during ER stress, namely ATF3, HSP27, Hmox1, HSP40, and CHOP/Gadd153. The secondary goal of the study was to investigate the role of DA D1 receptor stimulation on the expression of genes that participate in ER stress-mediated molecular events. We thus used quantitative PCR to confirm changes in the METH-responsive ER genes identified by the microarray analyses. We also measured the expression of these genes and of ATF4, ATF6, BiP/GRP78, and of GADD34 over a more extended time course. SCH23390 attenuated or blocked METH-induced increases in the expression of the majority of these genes. Western blot analysis revealed METH-induced increases in the expression of the antioxidant protein, Hmox1, which lasted for about 24 hours after the METH injection. Additionally, METH caused DA D1 receptor-dependent transit of the Hmox1 regulator protein, Nrf2, from cytosolic into nuclear fractions where the protein exerts its regulatory functions. When taken together, these findings indicate that SCH23390 can provide

  15. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    KAUST Repository

    Lemtiri-Chlieh, Fouad

    2011-12-19

    Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.

  16. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Lemtiri-Chlieh Fouad

    2011-12-01

    Full Text Available Abstract Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP, widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7, a Rho GDP/GTP exchange factor (Rho-GEF localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.

  17. 2009年新型甲型H1N1流感病毒血凝素基因进化及变异特征分析%Genetic evolution and variation of hemagglutinin gene of the novel A/H1N1 influenza pandemic virus in 2009

    Institute of Scientific and Technical Information of China (English)

    李淑华; 韩一芳; 谢佳新; 韩磊; 苏彤; 鹿文英; 曹广文

    2009-01-01

    目的 了解自2009年3月新型甲型H1N1流感流行以来,其主要免疫原件基因-HA基因的进化及氨基酸变异特性.方法 从NCBI下载2009年新型甲型H1N1流感病毒以及北美地区、欧洲地区、亚洲地区以往流行的甲型H1N1流感病毒HA基因序列,利用MEGA 4.0软件对所选序列进行基因进化系统发育树分析;对2009年新型甲型H1N1流感病毒HA基因的核苷酸同源性及氨基酸特异性进行分析,并与北美地区、欧洲地区、亚洲地区分离株进行比较.结果 2009年新型甲型HlNl流感病毒HA基因与2006-2007年美国A/swine/H1N1流感病毒同源性最高,核苷酸序列差异为0%~0.8%;与美国各州1930-2007年分离的A/swine/H1N1流感病毒具有明显的时间上的进化关系;与欧洲及亚洲地区A/swine/H1N1流感病毒进化无关.其重要的抗原性位点与A/human/H1N1流感病毒及流感疫苗株存在较大差异.全球流行半年多以来该病毒株没有发生明显变异.结论 2009年新型甲型H1N1流感病毒HA基因是北美A/swine/H1N1流感病毒长期进化的结果,目前尚未发现明显抗原位点的变异.%Objective To elucidate the characteristics of genetic evolution and variation trend of hemagglutinin ( HA). a major antigenic gene of the novel A/H1N1 influenza pandemic virus in 2009. Methods HA gene sequences of the novel A/H1N1 influenza pandemic virus in 2009, as well as that of the A/H1N1 influenza virus spread in North America, Europe and Asia, were downloaded from NCBI database. MEGA4.0 software was used to analyze the constructed phylogenetic tree of the selected sequences of HA gene. The nucleotide homology and amino acid specificity of the novel A/H1N1 influenza pandemic virus in 2009 were analyzed and compared with those in North America, Europe and Asia regions. Results HA gene of the novel A/H1N1 influenza pandemic virus in 2009 showed a highest homology (93. 2%-93. 4%) with the corresponding sequences of A/swine/H1N1 influenza

  18. Maqashidusy Syari'ah Dan Kloning

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    Asymuni Abdurrahman

    1997-06-01

    Full Text Available MASALAH kloning ini, merupakan masalah yang baru timbul sekalipun embrio masalah ini sudah lama dikenal ilmuan, terutama dikalangan ahli botani atau ilmu tumbuh-tumbuhan dan ilmu biologi. Pengertian kloning bersifat umum, tidak terbatas pada tumbuhan dan hewan saja. Tetapi juga dalam perkembangan ilmu rekayasa genetika dimungkinkan untuk dapat diterapkan pada manusia. Kloning dalam batas pelaksanaannya untuk tumbuh-tumbuhan dan hewan tidaklah menjadi permasalahan, tetapi akan menjadi permasalahan kalau sampai kloning ini diterapkan pada manusia yang dapat memproduksi manusia tanpa pernikahan. Sekalipun sampai sekarang belum berhasil kloning terhadap manusia, namun perlu mendapat antisipasi pemikiran dari segi syari'ah, khususnya dari segi maqashidusy syari'ah.

  19. SISTEM LEMBAGA KEUANGAN SHARI’AH

    Directory of Open Access Journals (Sweden)

    Shinta Dewianty

    2012-04-01

    Full Text Available Lembaga Keuangan Shari’ah merupakan embrio kekuatan ekonomi di negara ini, di zamannya ia mampu menjadi sistem yang bisa mensejahterakan umatnya. Di masa krisis, ia mampu lolos dari kebangkrutan, sekalipun tidak mendapat bantuan dana BLBI. Konsep yang mengandung keshari’ahan ini harus menjadi kekuatan baru dalam membangkitkan kembali perekonomian negeri ini. Sistem lembaga Keuangan Shari’ah ini berkembang pesat memainkan peranan penting dalam mengalokasikan sumber daya dan meningkatkan pembangunan ekonomi. Tulisan ini merupakan studi pustaka dimana penulis mencoba menjelaskan bagaimana sistem lembaga keuangan islam di berbagai Negara, dan kemudian di bandingkan dengan penerapan sistem lembaga keuangan di Indonesia.

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

    Science.gov (United States)

    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.

  1. TCDD-induced transcriptional profiles in different mouse strains that have an identical AhR genotype

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qing; Suzuki, Junko S.; Tohyama, Chiharu; Ohsako, Seiichiroh [Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Tsukuba (Japan); Takei, Teiji [Environmental Health and Safety Division, Ministry of the Environment, Kasumigaseki, Tokyo (Japan); Lin, Tinmin; Peterson, R.E. [Wisconsin Univ., Wisconsin, MA (United States). School of Pharmacy and Molecular and Environmental Toxicology Center

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that is known to cause hepatotoxicity, teratogenicity and carcinogenicity. A characteristic feature in the toxicity of TCDD is exceptionally large differences in susceptibility among animal species or even strains belonging to the same species. These strain differences in susceptibility to TCDD have now been elucidated to be due to the difference in ligand binding affinity or transcriptional activity of the aryl hydrocarbon receptor (AhR). Actually the C57BL/6 type AhR (AhR{sup b}) showed 6-fold higher ligand binding affinity than the DBA/2 type AhR (AhR{sup d}). The H/W rat AhR has a C-terminal truncation of the transactivating domain compared to the L-E rat AhR. On the other hand, there is considerable species variability in response sensitivity to TCDD that cannot be ascribed simply to polymorphisms of the AhR gene. A non-AhR gene susceptibility loci for hepatic porphyria has been observed in mice treated with iron compounds prior to TCDD injection by using a quantitative trait locus analysis of an F2 intercross between susceptible C57BL/6 and resistant DBA/2 stains. In the rat, a gene B with Han/Wistar type AhR is likely to be involved in resistance to TCDD lethality. These observations suggest that other modulating genes, so-called ''modifier genes'', have profound effects on the AhR-mediated gene expression phenotype. Based on the nucleotide sequence of the AhR coding region, the BALB/c, CBA/J, and C3H/He mouse strains are clustered together on a single branch. In the present study, we try to confirm the existence of modifiers by using microarray analysis to examine hepatic gene expression after TCDD exposure in BALB/c, CBA/J, and C3H/He mice. To recognize the existence of a modifier besides the AhR, it is a prerequisite experimental condition that the analyzed strains have an identical AhR genotype. Therefore, we selected BALB/c, CBA/J, and C3H/He mice as the model

  2. Effect of Calpain inhibitor I on glucocorticoid receptor-dependent degradation and its transactivation ability

    Institute of Scientific and Technical Information of China (English)

    程晓刚; 粟永萍; 罗成基; 刘晓宏

    2004-01-01

    Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocoaicoid receptor, and enhances glucocorticoid receptor transactivation ability.

  3. AL-KAFA’AH FI AL-NIKAH

    Directory of Open Access Journals (Sweden)

    Najmah Sayuti

    2015-11-01

    Full Text Available Kafa'ah in marriage is basically equality, suitability and proportionality between the prospective couples getting married. Humans are required to kafa'ah in religion and religiosity. Non-Muslims can't kafa'ah with Muslims because of inequalities in beliefe. Some kafa'ah that should be considered in marriage is nasab, religion, belief or religiosity, profession, liberty and property.

  4. PGE2 released by primary sensory neurons modulates Toll-like receptor 4 activities through an EP4 receptor-dependent process.

    Science.gov (United States)

    Tse, Kai-Hei; Chow, Kevin B S; Wise, Helen

    2016-04-15

    Exogenous prostaglandin E2 (PGE2) displays mixed regulatory properties with regard to inflammatory gene expression in dorsal root ganglion (DRG) cells. We show here that endogenously-produced nanomolar concentrations of PGE2, such as that generated in response to Toll-like receptor 4 (TLR4) stimulation, inhibits both cyclooxygenase-2 (COX-2) and tumour necrosis factor alpha (TNFα) mRNA expression in DRG cells in an EP4 receptor-dependent manner. DRG neurons appear to be the major source of PGE2 in the DRG and likely serve as both an autocrine and paracrine system for limiting over-activation of both DRG neurons and glial cells in response to TLR4 stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

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

    Science.gov (United States)

    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.

  7. In-flight AHS MTF measurements

    Science.gov (United States)

    Viallefont-Robinet, Françoise; Fontanilles, Guillaume; de Miguel, Eduardo

    2008-10-01

    The disposal of couples of images of the same landscape acquired with two spatial resolutions gives the opportunity to assess the in-flight Modulation Transfer Function (MTF) of the lower resolution sensor in the common spectral bands. For each couple, the higher resolution image stands for the landscape so that the ratio of the spectra obtained by FFT of the two images, gives the lower resolution sensor MTF. This paper begins with a brief recall of the method including the aliasing correction. The next step presents the data to be processed, provided by the Instituto Nacional de Tecnica Aeroespacial (INTA). The model of the AHS MTF is described. The presentation of the corresponding AHS results naturally follows. Last part of the paper consists in a comparison with other measurements: measurements obtained with the edge method and laboratory measurements.

  8. Doktrin Shi’ah Membelenggu Ukhuwwah

    Directory of Open Access Journals (Sweden)

    Moh. Hasyim Afandi

    2015-09-01

    Full Text Available Ukhuwah is a basic necessity for every human being. Either in religious life or society, man needs ukhuwah. Ukhuwah does not have to force someone equal in all respects. Ukhuwah principle is tolerance, mutual respect, mutual appriciation and not force. Indonesia is a diverse country, whether ethnic, religious, cultural or others. With Bhineka Tunggal Ika, diversity can be tied in a single container NKRI. This republic can be realized thanks to the struggle of leaders who promote ukhuwah. The emergence of Shi’ah ideology ukhuwah disturbing in this country. With the doctrine of takfir (which really only understand Shia’ah, the others infidels and leaders (believe that the imam is the supreme authority in religion and world. If this kind of ideology is left, the disintegration will happen. Because of the belief that they will not tolerate, respect, and appreciate other philosophies.

  9. Mengangkat "Sing Liyan" Untuk Formulasi Nilai Tambah Syari'ah

    OpenAIRE

    Iwan Triyuwono

    2011-01-01

    Abstract: Making Use “Sing Liyan”/ “The Other” to Formulate Shari’ah Value Added: This study attempts to formulate Shari’ah value-added as consequence of adopting Shari’ah Enterprise Theory (SET) as a basic theory of Shari’ah Accounting. The issue emerges as a result of a conflicting idea of whether Shari’ah accounting utilizes SET or Entity Theory (ET). For some reasons, this study implicitly prefers to SET than ET. Hence, the study is only concerned with value-added instead of income in the...

  10. Southeast Asian Sharī‘ahs

    Directory of Open Access Journals (Sweden)

    M.B. Hooker

    2013-08-01

    Full Text Available The Southeast Asian materials show that the sharī‘ah’s providing various pathways (through time and place for individual Muslims to follow when doing their duty to God, which is fidelity to Revealed Truth. There are many paths and it is pointless to insist upon an historical ‘purist’ mono-legacy, however attractive this might appear theoretically. The realities of life (economics, social structure, alternative philosophies, and so on dictate otherwise. Local sharī‘ahs adapt realities to Revelation irrespective of whether sources of legislation or forms of government are Muslim or non-Muslim this was never an issue in Southeast Asia. The localized sharī‘ahs were achieved via an acceptance of legal pluralism and hybridization of laws. The result is that Revealed obligations are phrased in local terms, change over time is allowed for, and the end result is a truly original and unique set of ‘Southeast Asian’ sharī‘ahs.Copyright (c 2014 by SDI. All right reserved.DOI: 10.15408/sdi.v20i2.387

  11. Neuregulin and BDNF induce a switch to NMDA receptor-dependent myelination by oligodendrocytes.

    Directory of Open Access Journals (Sweden)

    Iben Lundgaard

    2013-12-01

    Full Text Available Myelination is essential for rapid impulse conduction in the CNS, but what determines whether an individual axon becomes myelinated remains unknown. Here we show, using a myelinating coculture system, that there are two distinct modes of myelination, one that is independent of neuronal activity and glutamate release and another that depends on neuronal action potentials releasing glutamate to activate NMDA receptors on oligodendrocyte lineage cells. Neuregulin switches oligodendrocytes from the activity-independent to the activity-dependent mode of myelination by increasing NMDA receptor currents in oligodendrocyte lineage cells 6-fold. With neuregulin present myelination is accelerated and increased, and NMDA receptor block reduces myelination to far below its level without neuregulin. Thus, a neuregulin-controlled switch enhances the myelination of active axons. In vivo, we demonstrate that remyelination after white matter damage is NMDA receptor-dependent. These data resolve controversies over the signalling regulating myelination and suggest novel roles for neuregulin in schizophrenia and in remyelination after white matter damage.

  12. A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes.

    Science.gov (United States)

    Benford, Heather; Bolborea, Matei; Pollatzek, Eric; Lossow, Kristina; Hermans-Borgmeyer, Irm; Liu, Beihui; Meyerhof, Wolfgang; Kasparov, Sergey; Dale, Nicholas

    2017-05-01

    Hypothalamic tanycytes are glial-like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor-dependent mechanism. Here, we show that tanycytes in rodents respond to non-nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor. The initial sweet tastant-evoked response, which requires the presence of extracellular Ca(2+) , leads to release of ATP and a larger propagating Ca(2+) response mediated by P2Y1 receptors. In Tas1r2 null mice the proportion of glucose nonresponsive tanycytes was greatly increased in these mice, but a subset of tanycytes retained an undiminished sensitivity to glucose. Our data demonstrate that the sweet taste receptor mediates glucosensing in about 60% of glucosensitive tanycytes while the remaining 40% of glucosensitive tanycytes use some other, as yet unknown mechanism. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  13. Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR)-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli

    Science.gov (United States)

    Guruge, Keerthi S.; Yamanaka, Noriko; Sonobe, Miyuki; Fujizono, Wataru; Yoshioka, Miyako; Akiba, Masato; Yamamoto, Takehisa; Joshua, Derrick I.; Balakrishna, Keshava; Yamashita, Nobuyoshi; Kannan, Kurunthachalam; Tsutsui, Toshiyuki

    2015-01-01

    Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of

  14. Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Keerthi S Guruge

    Full Text Available Extracts of wastewater collected from 4 sewage treatment plants (STPs receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and

  15. Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR)-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli.

    Science.gov (United States)

    Guruge, Keerthi S; Yamanaka, Noriko; Sonobe, Miyuki; Fujizono, Wataru; Yoshioka, Miyako; Akiba, Masato; Yamamoto, Takehisa; Joshua, Derrick I; Balakrishna, Keshava; Yamashita, Nobuyoshi; Kannan, Kurunthachalam; Tsutsui, Toshiyuki

    2015-01-01

    Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of

  16. The antisense expression of AhPEPC1 increases seed oil production in peanuts (Arachis hypogaea L.

    Directory of Open Access Journals (Sweden)

    L. Pan

    2016-12-01

    Full Text Available Although phosphoenolpyruvate carboxylases (PEPCs are reported to be involved in fatty acid accumulation, nitrogen assimilation, and salt and drought stresses, knowledge regarding PEPC gene functions is still limited, particularly in peanuts (Arachis hypogaea L.. In this study, the antisense expression of the peanut PEPC isoform 1 (AhPEPC1 gene increased the lipid content by 5.7%–10.3%. This indicated that AhPEPC1 might be related to plant lipid accumulation. The transgenic plants underwent more root elongation than the wild-type under salinity stress. Additionally, the specific down regulation of the AhPEPC1 gene improved the salt tolerance in peanuts. This is the first report on the role of PEPC in lipid accumulation and salt tolerance in peanuts.

  17. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

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    Hana Apsari Pawestri

    2016-07-01

    5N1 and A/H1N1pdm09 Methods. We conducted Gen Bank National Center for Biotechnology Information (NCBI for A/H5N1 and A/H1N1pdm09 Influenza virus sequences database search started from 1997 until 2015. Data pertinent to this study is PB1 gene of A/H5N1 and A/H1N1pdm09 Influenza viruses. We conducted the multiple alignments to determine the various length and important mutation.   Results. The PB1-F2 sequences from the 3262 Influenza A/H5N1 and 2472 Influenza A/H1N1pdm09 were studied. The analysis showed that all Influenza A/H5N1 carrying the full length 90 amino acids of PB2-F1 sequences, except the Influenza pandemic A/H1N1 2009, only 87 amino acids. In addition, the mutation indicates the presence of a significant correlation with the virulence shown by Serine at nucleotide number 66 which replaces Asparagines (N66S. The mutation occurs in 8.5% of Influenza A/H5N1 and 0.5% of Influenza A/H1N1pdm09. Conclusion. Several varying length and important mutation of PB2-F1 sequences from different subtype of A/H5N1 and A/H1N1pdm09 were obtained which are indicating the positively selected in specific subtype due to introduction and adaptation into different host. The further studies are required to understanding this variability and contribution of PB1-F2 proteins in virulence and pathogenesis of influenza viruses. Key Words : Pathogenesis, Influenza virus, PB-F2 Protein

  18. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

    Directory of Open Access Journals (Sweden)

    Hana Apsari Pawestri

    2016-07-01

    5N1 and A/H1N1pdm09 Methods. We conducted Gen Bank National Center for Biotechnology Information (NCBI for A/H5N1 and A/H1N1pdm09 Influenza virus sequences database search started from 1997 until 2015. Data pertinent to this study is PB1 gene of A/H5N1 and A/H1N1pdm09 Influenza viruses. We conducted the multiple alignments to determine the various length and important mutation. Results. The PB1-F2 sequences from the 3262 Influenza A/H5N1 and 2472 Influenza A/H1N1pdm09 were studied. The analysis showed that all Influenza A/H5N1 carrying the full length 90 amino acids of PB2-F1 sequences, except the Influenza pandemic A/H1N1 2009, only 87 amino acids. In addition, the mutation indicates the presence of a significant correlation with the virulence shown by Serine at nucleotide number 66 which replaces Asparagines (N66S. The mutation occurs in 8.5% of Influenza A/H5N1 and 0.5% of Influenza A/H1N1pdm09. Conclusion. Several varying length and important mutation of PB2-F1 sequences from different subtype of A/H5N1 and A/H1N1pdm09 were obtained which are indicating the positively selected in specific subtype due to introduction and adaptation into different host. The further studies are required to understanding this variability and contribution of PB1-F2 proteins in virulence and pathogenesis of influenza viruses. Key Words : Pathogenesis, Influenza virus, PB-F2 Protein

  19. Intracellular Localization and Trafficking of Serine Proteinase AhSub and Cysteine Proteinase AhCP of Acanthamoeba healyi

    OpenAIRE

    Moon, E.-K.; Lee, S.-T.; Chung, D.-I.; Kong, H.-H.

    2006-01-01

    Proteinases have been proposed to play important roles in pathogenesis and various biologic actions in Acanthamoeba. Although genetic characteristics of several proteases of Acanthamoeba have been reported, the intracellular localization and trafficking of these enzymes has yet to be studied. In the present study, we analyzed the intracellular localization and trafficking of two proteinases, AhSub and AhCP, of Acanthamoeba healyi by transient transfection. Full-length AhSub-enhanced green flu...

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

    Science.gov (United States)

    Ghotbaddini, Maryam; Powell, Joann B

    2015-07-06

    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.

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

    Directory of Open Access Journals (Sweden)

    Maryam Ghotbaddini

    2015-07-01

    Full Text Available 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.

  2. Genetic structure of human A/H1N1 and A/H3N2 influenza virus on Corsica Island: phylogenetic analysis and vaccine strain match, 2006-2010.

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    Alessandra Falchi

    Full Text Available BACKGROUND: The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season. METHODS: Nasopharyngeal samples from 371 patients with influenza-like illness (ILI were collected by General Practitioners (GPs of the Sentinelles Network through a randomised selection routine. RESULTS: Phylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006-2007 to 2008-2009. Seasonal Corsican influenza A/H1N1 isolated during the 2007-2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008-2009 season. The A/H1N1 2009 (A/H1N1pdm strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E. The percentages of the perfect match vaccine efficacy, estimated by using the p(epitope model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene. CONCLUSION: The molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006-2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.

  3. Development and characterization of a green fluorescent protein-based rat cell bioassay system for detection of AH receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Bin; Denison, M. [California Univ., Davis, CA (United States). Dept. of Environmental Toxicology

    2004-09-15

    Proper epidemiological, risk assessment and exposure analysis of TCDD and related HAHs requires accurate measurements of these chemicals both in the species of interest and in various exposure matrices (i.e. biological, environmental, food and feed). While high-resolution instrumental analysis techniques are established for these chemicals, these procedures are very costly, time-consuming and are impractical for large scale sampling studies. Accordingly, numerous bioanalytical methods have been developed for the detection of these chemicals in extracts from a variety of matrices, the majority of which take the advantage of the ability of these chemicals to activate one or more aspects of the AhR-dependent mechanism of action. One of the most sensitive bioassay systems developed to date is the so-called CALUX (Chemically Activated Luciferase Expression) assay, which is based on novel recombinant cell lines that contain a stably transfected dioxin (AhR)-responsive firefly luciferase gene. Treatment of these cells with TCDD and related HAHs and polycyclic aromatic hydrocarbons (PAHs), as well as other AhR ligands, results in induction of reporter gene expression in a time-, dose-, AhR-, and chemical-specific manner. The level of reporter gene expression correlates with the total concentration of the TCDD-like AhR inducers (agonists) present in the sample. Although the firefly luciferase reporter gene contributes to the high degree of sensitivity of the assay, it also has limitations with respect to our need for a rapid and inexpensive bioassay for high-throughput screening analysis. Accordingly, we previously developed a stably transfected murine cell line containing an AhRresponsive enhanced green fluorescent protein (EGFP) reporter gene. This cell line provided us with a high-throughput cell bioassay system for identification and characterization of AhR agonists and antagonists. Here we have extended these studies and describe the development, optimization, and

  4. Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals.

    Science.gov (United States)

    Kaplan, Bryan S; Russier, Marion; Jeevan, Trushar; Marathe, Bindumadhav; Govorkova, Elena A; Russell, Charles J; Kim-Torchetti, Mia; Choi, Young Ki; Brown, Ian; Saito, Takehiko; Stallknecht, David E; Krauss, Scott; Webby, Richard J

    2016-01-01

    Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on

  5. Evaluation of 20 Ah Li Ion Cells

    Science.gov (United States)

    Smart, Marshall; Ratnakumar, B. V.; Huang, Charles K.; Surampudi, S.; Hill, Carole; Radzykewycz, Dan T.; Marsh, Richard A.

    1998-01-01

    Lithium ion cells of 20 Ah capacity were fabricated by Bluestar Advanced Technology Corporation, Canada under a developmental contract from US Air Force. In this paper, we report our studies on the evaluation of these cells under various test conditions. These include generic test conditions such as discharges and charges at different temperatures to understand the rate-limiting processes in the discharge/charge processes as a function of temperature, and cycle life under standard cycling conditions (100% DOD) at ambient temperature. In addition, tests are being done to ascertain the performance of the cells in the Mars 2001 Lander application, which includes pulse testing of the cells at 60 A and 40 A loads for 100 mS and 1 min., respectively at different states of charge and temperatures, and cycling at low temperature at partial depths of discharge.

  6. Ah receptor agonist activity in frequently consumed food items

    NARCIS (Netherlands)

    Waard, de W.J.; Aarts, J.M.M.J.G.; Peijnenburg, A.A.C.M.; Kok, de T.M.C.M.; Schooten, van F.J.; Hoogenboom, L.A.P.

    2008-01-01

    The aryl hydrocarbon receptor (AhR) receives much attention for its role in the toxicity of dioxins and dioxin-like polychlorinated biphenyls. However, many other compounds have also been reported to bind and activate AhR, of which natural food components are of special interest from a human health

  7. Ah receptor agonist activity in frequently consumed food items

    NARCIS (Netherlands)

    Waard, de W.J.; Aarts, J.M.M.J.G.; Peijnenburg, A.A.C.M.; Kok, de T.M.C.M.; Schooten, van F.J.; Hoogenboom, L.A.P.

    2008-01-01

    The aryl hydrocarbon receptor (AhR) receives much attention for its role in the toxicity of dioxins and dioxin-like polychlorinated biphenyls. However, many other compounds have also been reported to bind and activate AhR, of which natural food components are of special interest from a human health

  8. Evolusi Sharî‘ah dan Wacana Fiqih

    Directory of Open Access Journals (Sweden)

    Abu Yasid

    2014-01-01

    Full Text Available Sharî‘ah has always been deemed as an integral part of Muslims life. As a binding and commanding divine law, Sharî‘ah has in other words been internalized in the being and existence of Muslims through their obedience and regular practice. The question that this paper tries to answer is whether Sharî‘ah is divine and transcendent, or is it evolving from being transcendent to becoming mere ideas and legal dictum of the ulama? To delve on this question the paper begins by saying that any legal formulation does stem from observation of social reality. Given the changing nature of social reality –we argue- the product of legal extrapolation does exhibit some form of evolution. We further argue that so long as the heart of the divine law is human interest (maşlahah both worldly and heavenly, Sharî‘ah cannot escape from the law of evolution considering that the interest of the vast span of humanity differs from one setting to another. That is why many jurists speak of the Maqasid al-Sharî‘ah (the aims of Sharî‘ah implying that Sharî‘ah does evolve given the multiplicity of these aims. Simply speaking, the paper is directed toward proving that Sharî‘ah cannot be seen as stagnant and that it is subjected–like any other forms of knowledge–to the law of evolution.

  9. Development of a platoon driving AHS; AHS jikkensha ni okeru gunsoko seigyo no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Y.; Inoue, H. [Nissan Motor Co. Ltd., Tokyo (Japan)

    1997-10-01

    Nissan and the Public Work Research Institute of the Ministry of Construction are developing an Automated Highway System. We are investigating a longitudinal control system in AHS. In this paper, a vehicle control method using two actuators an engine and a brake, is described. Experimental and simulated results are shown. A Platoon driving control method using road-to-vehicle and vehicle-to-vehicle communication is described. And the influence of the communication on the control performance is shown by experiments and simulation. The effects of the communication device and control device mentioned above are verified by experimental results in an AHS field test conducted in September 1996 on a dosed highway. 5 refs., 8 figs.

  10. RASIONALITAS KONVERSI BANK KONVENSIONAL KE BANK SYARI’AH

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    Aji Damanuri

    2016-02-01

    Aji Damanuri   Abstract: Shari>’ah banking, for the last ten years, has increased in prosperity not only at the quantity of conventional banks but also at the count of assets and customers. This economical opportunity drives amount of conventional banks both to convert their institutions to be shari>’ah banks and to open officially shari>’ah platform units with their own assets. This system takes a significant question, is the conversion effected by both banker ideological factor and capitalists or pure economical rational calculation? Is a religious consideration linked to economical rationality? This paper is to elaborate the conversion using not only ‘choice theory’ (teori pilihan but also ‘rational action’ (tindakan rasional to seek religious action possibility in a reasonable way of shari>’ah banking.   Keywords: shari>’ah bank, conversion, rational action, religiosity.

  11. BCL6--regulated by AhR/ARNT and wild-type MEF2B--drives expression of germinal center markers MYBL1 and LMO2.

    Science.gov (United States)

    Ding, Jie; Dirks, Wilhelm G; Ehrentraut, Stefan; Geffers, Robert; MacLeod, Roderick A F; Nagel, Stefan; Pommerenke, Claudia; Romani, Julia; Scherr, Michaela; Vaas, Lea A I; Zaborski, Margarete; Drexler, Hans G; Quentmeier, Hilmar

    2015-06-01

    Genetic heterogeneity is widespread in tumors, but poorly documented in cell lines. According to immunoglobulin hypermutation analysis, the diffuse large B-cell lymphoma cell line U-2932 comprises two subpopulations faithfully representing original tumor subclones. We set out to identify molecular causes underlying subclone-specific expression affecting 221 genes including surface markers and the germinal center oncogenes BCL6 and MYC. Genomic copy number variations explained 58/221 genes differentially expressed in the two U-2932 clones. Subclone-specific expression of the aryl-hydrocarbon receptor (AhR) and the resulting activity of the AhR/ARNT complex underlaid differential regulation of 11 genes including MEF2B. Knock-down and inhibitor experiments confirmed that AhR/ARNT regulates MEF2B, a key transcription factor for BCL6. AhR, MEF2B and BCL6 levels correlated not only in the U-2932 subclones but in the majority of 23 cell lines tested, indicting overexpression of AhR as a novel mechanism behind BCL6 diffuse large B-cell lymphoma. Enforced modulation of BCL6 affected 48/221 signature genes. Although BCL6 is known as a transcriptional repressor, 28 genes were up-regulated, including LMO2 and MYBL1 which, like BCL6, signify germinal center diffuse large B-cell lymphoma. Supporting the notion that BCL6 can induce gene expression, BCL6 and the majority of potential targets were co-regulated in a series of B-cell lines. In conclusion, genomic copy number aberrations, activation of AhR/ARNT, and overexpression of BCL6 are collectively responsible for differential expression of more than 100 genes in subclones of the U-2932 cell line. It is particularly interesting that BCL6 - regulated by AhR/ARNT and wild-type MEF2B - may drive expression of germinal center markers in diffuse large B-cell lymphoma.

  12. Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

    Science.gov (United States)

    Dijkstra, Frederika; Jonges, Marcel; van Beek, Ruud; Donker, Gé A; Schellevis, François G; Koopmans, Marion; van der Sande, Marianne A.B; Osterhaus, Albert D.M.E; Boucher, Charles A.B; Rimmelzwaan, Guus F; Meijer, Adam

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivir resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. PMID:22253652

  13. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013.

    Science.gov (United States)

    Wang, D; Yang, L; Gao, R; Zhang, X; Tan, Y; Wu, A; Zhu, W; Zhou, J; Zou, S; Li, Xiyan; Sun, Y; Zhang, Y; Liu, Y; Liu, T; Xiong, Y; Xu, J; Chen, L; Weng, Y; Qi, X; Guo, J; Li, Xiaodan; Dong, J; Huang, W; Zhang, Y; Dong, L; Zhao, X; Liu, L; Lu, J; Lan, Y; Wei, H; Xin, L; Chen, Y; Xu, C; Chen, T; Zhu, Y; Jiang, T; Feng, Z; Yang, W; Wang, Y; Zhu, H; Guan, Y; Gao, G F; Li, D; Han, J; Wang, S; Wu, G; Shu, Y

    2014-06-26

    A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans. The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic.

  14. PERDA Sharî‘ah antara Legalitas dan Prospek

    Directory of Open Access Journals (Sweden)

    Mudzakir Mudzakir

    2014-01-01

    Full Text Available Many have been done to study the problem of Sharî‘ah and other related issues. But little has been done to investigate the notion of the application of Sharî‘ah in Indonesia in the form of regional law, otherwise known as Perda Sharî‘ah. Apart from its importance and sensitivity, the Perda Sharî‘ah is quite ignored by the academic circle in this country. It is toward filling this gap that this paper is written. It is interested first in discussing the nature of Syariah, its values, history, and sources. Then it moves to the currents of thought and modes of interpretation as far as Sharî‘ah is concerned. It finally discusses the ways Sharî‘ah is applied in daily live and how a country like Indonesia –or rather certain districts in it- are involved in formalizing Sharî‘ah as their regional law. The main argument of this paper is that, Islam is not solely about law. Islam is a religion of ethics, morality, belief, and spirituality. Islam is also a way of life, the consequence of which being that it should be comprehended universally as comprehensive system of living. Hence, we argue, that the application of Islam in the form of regional law would mean a simplification of the more universal form of Islam, and a reduction of the more holistic message of the religion.

  15. Women and Shari‘ah Law: Lessons from Aceh

    Directory of Open Access Journals (Sweden)

    Asna Husin

    2015-12-01

    Full Text Available This study surveys the role of women in the development of shari`ah from the introduction of Islam to Aceh in the 12th centurydown to the modern erawith the formal adoption of Islamic law by an Indonesian parliamentary Bill on Aceh’s Special Status in 1999. After briefly exploring this history, we examine contemporary debates on the current implementation of Islamic law by means of five women of differing backgrounds in this Indonesian province. We review historical documents and existing literature as well as qanuns of Aceh (local regulations which stipulate shari`ah requirements. We also interview the five women, including one whose husband and another who herself were subjected to shari`ah punishment. The results are complex reflecting the intricacy of contemporary understandings of the shari`ah and the issues surrounding rights of women in Islamic law. One voice represents her agreement to the shari`ah punishment of her husband on account of its positive outcome for her family. The other four are critical of the current implementation of the shari`ah in Aceh, yet are not opposed to it; these ladies argue for women-friendly shari`ah.

  16. Two patients with complete defects in interferon gamma receptor-dependent signaling.

    NARCIS (Netherlands)

    Noordzij, J.G.; Hartwig, N.G.; Verreck, F.A.; Bruin-Versteeg, S. de; Boer, T. de; Dissel, J.T. van; Groot, R. de; Ottenhoff, T.H.M.; Dongen, J.J.M. van

    2007-01-01

    Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon-gamma receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here re

  17. The Chromatin Remodeler CHD8 Is Required for Activation of Progesterone Receptor-Dependent Enhancers

    Science.gov (United States)

    Giannopoulou, Eugenia G.; Soronellas, Daniel; Vázquez-Chávez, Elena; Vicent, Guillermo P.; Elemento, Olivier; Beato, Miguel; Reyes, José C.

    2015-01-01

    While the importance of gene enhancers in transcriptional regulation is well established, the mechanisms and the protein factors that determine enhancers activity have only recently begun to be unravelled. Recent studies have shown that progesterone receptor (PR) binds regions that display typical features of gene enhancers. Here, we show by ChIP-seq experiments that the chromatin remodeler CHD8 mostly binds promoters under proliferation conditions. However, upon progestin stimulation, CHD8 re-localizes to PR enhancers also enriched in p300 and H3K4me1. Consistently, CHD8 depletion severely impairs progestin-dependent gene regulation. CHD8 binding is PR-dependent but independent of the pioneering factor FOXA1. The SWI/SNF chromatin-remodelling complex is required for PR-dependent gene activation. Interestingly, we show that CHD8 interacts with the SWI/SNF complex and that depletion of BRG1 and BRM, the ATPases of SWI/SNF complex, impairs CHD8 recruitment. We also show that CHD8 is not required for H3K27 acetylation, but contributes to increase accessibility of the enhancer to DNaseI. Furthermore, CHD8 was required for RNAPII recruiting to the enhancers and for transcription of enhancer-derived RNAs (eRNAs). Taken together our data demonstrate that CHD8 is involved in late stages of PR enhancers activation. PMID:25894978

  18. Two patients with complete defects in interferon gamma receptor-dependent signaling.

    NARCIS (Netherlands)

    Noordzij, J.G.; Hartwig, N.G.; Verreck, F.A.; Bruin-Versteeg, S. de; Boer, T. de; Dissel, J.T. van; Groot, R. de; Ottenhoff, T.H.M.; Dongen, J.J.M. van

    2007-01-01

    Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon-gamma receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here

  19. The chromatin Remodeler CHD8 is required for activation of progesterone receptor-dependent enhancers.

    Science.gov (United States)

    Ceballos-Chávez, María; Subtil-Rodríguez, Alicia; Giannopoulou, Eugenia G; Soronellas, Daniel; Vázquez-Chávez, Elena; Vicent, Guillermo P; Elemento, Olivier; Beato, Miguel; Reyes, José C

    2015-04-01

    While the importance of gene enhancers in transcriptional regulation is well established, the mechanisms and the protein factors that determine enhancers activity have only recently begun to be unravelled. Recent studies have shown that progesterone receptor (PR) binds regions that display typical features of gene enhancers. Here, we show by ChIP-seq experiments that the chromatin remodeler CHD8 mostly binds promoters under proliferation conditions. However, upon progestin stimulation, CHD8 re-localizes to PR enhancers also enriched in p300 and H3K4me1. Consistently, CHD8 depletion severely impairs progestin-dependent gene regulation. CHD8 binding is PR-dependent but independent of the pioneering factor FOXA1. The SWI/SNF chromatin-remodelling complex is required for PR-dependent gene activation. Interestingly, we show that CHD8 interacts with the SWI/SNF complex and that depletion of BRG1 and BRM, the ATPases of SWI/SNF complex, impairs CHD8 recruitment. We also show that CHD8 is not required for H3K27 acetylation, but contributes to increase accessibility of the enhancer to DNaseI. Furthermore, CHD8 was required for RNAPII recruiting to the enhancers and for transcription of enhancer-derived RNAs (eRNAs). Taken together our data demonstrate that CHD8 is involved in late stages of PR enhancers activation.

  20. Whole-genome sequences of influenza A(H3N2 viruses isolated from Brazilian patients with mild illness during the 2014 season

    Directory of Open Access Journals (Sweden)

    Paola Cristina Resende

    2015-02-01

    Full Text Available The influenza A(H3N2 virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in South America. In this study we evaluate five whole genome sequences of influenza A(H3N2 viruses detected in patients with mild illness collected from January-March 2014. To sequence the genomes, a new generation sequencing (NGS protocol was performed using the Ion Torrent PGM platform. In addition to analysing the common genes, haemagglutinin, neuraminidase and matrix, our work also comprised internal genes. This was the first report of a whole genome analysis with Brazilian influenza A(H3N2 samples. Considerable amino acid variability was encountered in all gene segments, demonstrating the importance of studying the internal genes. NGS of whole genomes in this study will facilitate deeper virus characterisation, contributing to the improvement of influenza strain surveillance in Brazil.

  1. EDUKASI MARKETING BANK SYARÎ’AH

    Directory of Open Access Journals (Sweden)

    Wadhan Wadhan

    2013-08-01

    Full Text Available Abstract: Marketing is a significant aspect to increase consumer trust. Hence, it is essential to educate the consumer with the lesson of the importance of syarî’ah products concerning the marketing aspects. In fact, many banks serves the customer with syariah service in Indonesia.  The basic concept of spiritual marketing is the managements of creation, taste, heart and work (the implementation. Those concepts are under the guidence of faith integrity, obidience, and loyality to Allâh swt. The key of ethics and moral of business is truly placed on the doers. A Muslim busines manager must hold tightly the ethic and moral of business that cope –khusn al-huluq, trusty, dan tolerant. There are three marketing strategies of syariah banking; marker driven strategic, viral marketing way, and fish net strategy. Element of  mega marketing that had been intruduced by Rasûlullâh since the fifteenth century, and now can be adopted to any kinds of businesses including syariah banking. Key Words: Marketing, Marketer, dan Mega Marketing  

  2. Disruption of contact inhibition in rat liver epithelial cells by various types of AhR ligands

    Energy Technology Data Exchange (ETDEWEB)

    Vondracek, J.; Chramostova, K.; Kozubik, A. [Institute of Biophysics, Brno (Czech Republic); Krcmar, P.; Machala, M. [Veterinary Research Institute, Brno (Czech Republic)

    2004-09-15

    cytochrome P450 1A1 (CYP1A1) mRNA expression, a model AhR-dependent target gene. The results are compared with data on the effects of both persistent and non-persistent AhR ligands on WB-F344 cells.

  3. Full-genome analysis of avian influenza A(H5N1) virus from a human, North America, 2013.

    Science.gov (United States)

    Pabbaraju, Kanti; Tellier, Raymond; Wong, Sallene; Li, Yan; Bastien, Nathalie; Tang, Julian W; Drews, Steven J; Jang, Yunho; Davis, C Todd; Fonseca, Kevin; Tipples, Graham A

    2014-05-01

    Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found.

  4. AhR Activation Underlies the CYP1A Autoinduction by A-998679 in Rats

    Directory of Open Access Journals (Sweden)

    Michael J. Liguori

    2012-10-01

    Full Text Available 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, 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.

  5. Shari’ah Compliant Finance: Toward Economic Jihad

    Science.gov (United States)

    2010-04-12

    not definitively possess the said item. 21 Murabaha: A Cost-Plus Financing Methodology Similarly, a shepherd cannot sell an unborn calf, even if the...denying Islam as the one true religion is an apostate and subject to a death penalty. The Shari’ah law provides a legal context for killing non-believers...under Allah’s guidance. Again, Westerners show surprise when individuals are put to death under Shari’ah law for seemingly everyday missteps and

  6. Coactivator Recruitment of AhR/ARNT1

    Directory of Open Access Journals (Sweden)

    Alexander Endler

    2014-06-01

    Full Text Available A common feature of nuclear receptors (NRs is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of the specific genes in the nucleus. Another common feature of NRs is their dependence on coactivators, which bridge the basic transcriptional machinery and other cofactors to the target genes, in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase (HAT function. In this review, we focus on our recent findings related to the recruitment of steroid receptor coactivator 1 (SRC1/NCoA1 by the estrogen receptor-α (ERα and by the arylhydrocarbon receptor/arylhydrocarbon receptor nuclear translocator 1 (AhR/ARNT1 complex. We also describe the extension of our previously published findings regarding the binding between ARNT1.1 exon16 and SRC1e exon 21, via in silico analyses of androgen receptor (AR NH2-carboxyl-terminal interactions, the results of which were verified by in vitro experiments. Based on these data, we suggest a newly derived tentative binding site of nuclear coactivator 2/glucocorticoid receptor interacting protein-1/transcriptional intermediary factor 2 (NCOA-2/ GRIP-1/TIF-2 for ARNT1.1 exon 16. Furthermore, results obtained by immunoprecipitation have revealed a second leucine-rich binding site for hARNT1.1 exon 16 in SRC1e exon 21 (LSSTDLL. Finally, we discuss the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD as an endocrine disruptor for estrogen related transcription.

  7. Fatal intoxications associated with the designer opioid AH-7921.

    Science.gov (United States)

    Kronstrand, R; Thelander, G; Lindstedt, D; Roman, M; Kugelberg, F C

    2014-10-01

    AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a designer opioid with ∼80% of morphine's µ-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography-MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 µg/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.

  8. Dose- and time-dependent expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in PCB-, B[a]P-, and TBT-exposed intertidal copepod Tigriopus japonicus.

    Science.gov (United States)

    Kim, Bo-Mi; Rhee, Jae-Sung; Hwang, Un-Ki; Seo, Jung Soo; Shin, Kyung-Hoon; Lee, Jae-Seong

    2015-02-01

    The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (ARNT) genes from the copepod Tigriopus japonicus (Tj) were cloned to examine their potential functions in the invertebrate putative AhR-CYP signaling pathway. The amino acid sequences encoded by the Tj-AhR and Tj-ARNT genes showed high similarity to homologs of Daphnia and Drosophila, ranging from 68% and 70% similarity for the AhR genes to 56% for the ARNT genes. To determine whether Tj-AhR and Tj-ARNT are modulated by environmental pollutants, transcriptional expression of Tj-AhR and Tj-ARNT was analyzed in response to exposure to five concentrations of polychlorinated biphenyl (PCB 126) (control, 10, 50, 100, 500 μg L(-1)), benzo[a]pyrene (B[a]P) (control, 5, 10, 50, 100 μg L(-1)), and tributyltin (TBT) (control, 1, 5, 10, 20 μg L(-1)) 24h after exposure. A time-course experiment (0, 3, 6, 12, 24h) was performed to analyze mRNA expression patterns after exposure to PCB, B[a]P, and TBT. T. japonicus exhibited dose-dependent and time-dependent upregulation of Tj-AhR and Tj-ARNT in response to pollutant exposure, and the degree of expression was dependent on the pollutant, suggesting that pollutants such as PCB, B[a]P, and TBT modulate expression of Tj-AhR and Tj-ARNT genes in the putative AhR-CYP signaling pathway.

  9. Phylogenetic analysis of hemagglutinin (HA) gene of the novel avian influenza virus A/H7N9%新型甲型H7N9流感病毒血凝素基因进化分析

    Institute of Scientific and Technical Information of China (English)

    关蔚; 李自雄; 林吉; 韩一芳; 苏彤; 殷建华; 张宏伟; 曹广文

    2013-01-01

    目的 探讨2013年4月流行的新型甲型H7N9禽流感病毒的表面蛋白血凝素(HA)基因的进化,以及氨基酸的变异情况.方法 从美国国家生物技术信息中心(NCBI)和全球禽流感基因共享数据库(GISAID)中下载H7N9流感病毒以及有代表性的H7N2、H7N3、H7N7亚型流感病毒的HA基因序列,运用Molecular Evolutionary Genetics Analysis (MEGA)version 5.05软件进行序列分析,用邻接法构建基因进化树;通过氨基酸序列分析HA蛋白受体结合位点、糖基化位点和裂解位点的变化.结果 2013年新型甲型H7N9流感病毒与2011年浙江禽类H7N3流感病毒株(JQ906573.1)的相似性达到95.3%~95.6%;受体结合位点氨基酸发生变异,为Q226L,5个糖基化位点高度保守;HA裂解位点位于aa339和aa340之间,仅有1个碱性氨基酸:R.结论 2013年新型甲型H7N9流感病毒HA基因是由中国禽类H7亚型进化而来,Q226L变异导致的受体结合位点的变化可能是新型流感病毒具有人感染性的原因.%Objective To investigate the evolution and variations in coding amino acids of hemagglutinin (HA) gene of the novel avian influenza virus H7N9 in 2013 epidemic.Methods The HA gene sequences of influenza virus H7N9,H7N2,H7N3 and H7N7 subtypes were downloaded from the database of The National Center for Biotechnology Information (NCBI) and The Global Initiative on Sharing All Influenza Data (GISAID).MEGA 5.05 software was used for sequence analysis and NJ method was used for constructing the phylogenetic trees.The amino acid sequences at the receptor binding sites,glycosylation sites,and cleavage sites was aligned and analyzed.Results The HA genes this novel A/H7N9 virus in 2013 shared a 95.3%-95.6% similarity with JQ906573.1|Zhejiang (H7N3 virus) isolated in 2011.The most important variation in this novel H7N9 isolates was found at the receptor binding site:Q226L.The 5 glycosylation sites were highly conservative.One basic amino acid (R) at the HA

  10. SYARI’AH DALAM PERSPEKTIF PELAKU BISNIS MLM SYARI’AH AHADNET INTERNASIONAL ( Studi Kasus di Kota Semarang

    Directory of Open Access Journals (Sweden)

    Choirul Huda

    2016-05-01

    Full Text Available PT. Ahadnet International, a business Multi Level Marketing (MLM Syariah, is a MLM business operations based on the principles of syari'ah . The business attracted many people from among Muslims because it offers businesses with marketing Islamic halal products and toyyib. No doubt, many Muslims were later merged into the Ahadnet MITRANIAGA. Nevertheless, the Muslims interests of this business does not mean not raising the issue. Labeling the word “Syariah” is attached to the naming MLM International Syari’ah Ahadnet it needs proper interpretation. Wrong interpretation of the word shariah for the Ahadnet International MLM syari’ah business will bring counterproductive, both for the company, MITRANIAGA and for Islam itself. Seeing this phenomenon, it is through this study, researchers are trying to see how far the understanding of the actors (MITRANIAGA International Ahadnet the term shari’ah. Their understanding of Shari’ah will affect the way they work on the syariah business in genera,  particularly MLM syari’ah business

  11. Antibacterial efficacy of AH Plus and AH26 sealers mixed with amoxicillin, triple antibiotic paste and nanosilver

    Science.gov (United States)

    Kangarlou, Ali; Neshandar, Rojin; Matini, Negin; Dianat, Omid

    2016-01-01

    Background. Elimination of bacteria from the root canal system is one of the aims of endodontic treatment; hence the incorporation of antibiotics into sealers can increase their antimicrobial efficacy. The aim of the present study was to determine the in vitro antimicrobial effects of AH26 and AH Plus sealers mixed with amoxicillin, triple antibiotic paste and nanosilver on Enterococcus faecalis. Methods. In this experiment, amoxicillin, triple antibiotic paste and nanosilver powder were added at 10% of the total sealer weight to AH26 and AH Plus sealers and then cultured freshly or after 1, 3, and 7 days with suspension of E. faecalis for 24 hours. The zones of growth inhibition for E. faecalis were evaluated in each group. Results. Incorporation of nanosilver did not increase antibacterial effects of the sealers. Sealers combined with amoxicillin exhibited the highest antibacterial efficacy in fresh condition. In the set specimens, the results demonstrated that the mixture of sealers and triple antibiotic pastes exhibited the greatest antibacterial efficacy. Conclusion. Amoxicillin and triple antibiotic paste significantly improved the antibacterial properties of AH Plus and AH26 sealers. Such properties decreased with time, but the use of sealer-amoxicillin/triple paste combination was still superior to using sealers alone or in combination with nanosilver. PMID:28096947

  12. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.

    Science.gov (United States)

    Wedde, Marianne; Biere, Barbara; Wolff, Thorsten; Schweiger, Brunhilde

    2015-10-01

    This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic analysis of the hemagglutinin (HA) genes of both subtypes revealed similar evolution of the HA variants that were also seen worldwide with minor exceptions. The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since 2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were detected late in the 2009-2010 season. With respect to A(H3N2), we found herald strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were predominantly seen for minor and not for major HA clades. Generally, amino acid substitutions were most frequently found in the globular domain, including substitutions near the antigenic sites or the receptor binding site. Differences between both influenza A subtypes were seen with respect to the position of the indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more substitutions in the stem region than in the antigenic sites. In contrast, in A(H3N2) viruses most changes were identified in the major antigenic sites and five changes of potential glycosylation sites were identified in the head of the HA monomer. Interestingly, we found in seasons with less influenza activity a relatively high increase of substitutions in the head of the HA in both subtypes. This might be explained by the fact that mutations under negative selection are subsequently compensated by secondary mutations to restore important functions e.g. receptor binding properties. A better knowledge of basic evolution strategies of influenza viruses will contribute to the refinement of predictive mathematical models for identifying novel antigenic drift variants.

  13. Aryl hydrocarbon receptor (AhR agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

    Directory of Open Access Journals (Sweden)

    Schlezinger Jennifer J

    2003-12-01

    Full Text Available Abstract Background Bone marrow stromal cells produce cytokines required for the normal growth and development of all eight hematopoietic cell lineages. Aberrant cytokine production by stromal cells contributes to blood cell dyscrasias. Consequently, factors that alter stromal cell cytokine production may significantly compromise the development of normal blood cells. We have shown that environmental chemicals, such as aromatic hydrocarbon receptor (AhR agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell function. Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, to alter stromal cell cytokine responses. Methods Bone marrow stromal cells were treated with AhR agonists and bacterial lipopolysaccharide (LPS to mimic innate inflammatory cytokine responses and to study the effects of AhR ligands on those responses. Steady state cytokine RNA levels were screened by RNAse protection assays (RPA and quantified by real-time PCR. Cytokine (IL-6 protein production was measured by ELISA. NF-κB EMSAs were used to study IL-6 transcriptional regulation. Results RPAs indicated that AhR+ bone marrow stromal cells consistently up-regulated genes encoding IL-6 and LIF in response to LPS, presumably through activation of Toll-like receptor 4. Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was reflected in a profound down-regulation of IL-6 protein induction, with DMBA and TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-κB binding to IL-6 promoter sequences, an event known to induce IL-6 transcription, indicated a significant decrease in

  14. Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study.

    Science.gov (United States)

    Jensen, Brenda A; Leeman, Rebecca J; Schlezinger, Jennifer J; Sherr, David H

    2003-12-16

    Bone marrow stromal cells produce cytokines required for the normal growth and development of all eight hematopoietic cell lineages. Aberrant cytokine production by stromal cells contributes to blood cell dyscrasias. Consequently, factors that alter stromal cell cytokine production may significantly compromise the development of normal blood cells. We have shown that environmental chemicals, such as aromatic hydrocarbon receptor (AhR) agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell function. Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to alter stromal cell cytokine responses. Bone marrow stromal cells were treated with AhR agonists and bacterial lipopolysaccharide (LPS) to mimic innate inflammatory cytokine responses and to study the effects of AhR ligands on those responses. Steady state cytokine RNA levels were screened by RNAse protection assays (RPA) and quantified by real-time PCR. Cytokine (IL-6) protein production was measured by ELISA. NF-kappaB EMSAs were used to study IL-6 transcriptional regulation. RPAs indicated that AhR+ bone marrow stromal cells consistently up-regulated genes encoding IL-6 and LIF in response to LPS, presumably through activation of Toll-like receptor 4. Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was reflected in a profound down-regulation of IL-6 protein induction, with DMBA and TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-kappaB binding to IL-6 promoter sequences, an event known to induce IL-6 transcription, indicated a significant decrease in the LPS-mediated induction of DNA-binding Rel

  15. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

  16. Improving global influenza surveillance: trends of A(H5N1 virus in Africa and Asia

    Directory of Open Access Journals (Sweden)

    Escorcia Magdalena

    2012-01-01

    Full Text Available Abstract Background Highly pathogenic avian influenza A(H5N1 viruses are an important health problem in many Asian and African countries. The current increase in human cases demonstrates that influenza A(H5N1 is still a significant global pandemic threat. Many health organizations have recognized the need for new strategies to improve influenza global surveillance. Specifically, the World Health Organization through the global technical consultation for influenza surveillance have called for a detailed picture of the current limitations, especially at the nation level, to evaluate, standardize and strength reporting systems. The main goal of our study is to demonstrate the value of genetic surveillance as part of a strategic surveillance plan. As a proof of concept, we evaluated the current situation of influenza A(H5N1 in Asian and Africa. Results Our analysis revealed a power-law distribution in the number of sequences of A(H5N1 viruses analyzed and/or reported to influenza surveillance networks. The majority of the Asian and African countries at great risk of A(H5N1 infections have very few (approximately three orders of magnitude sequenced A(H5N1 viruses (e.g. hemagglutinin genes. This suggests that countries under pandemic alert for avian influenza A(H5N1 have very limited participation (e.g. data generation, genetic analysis and data share in avian influenza A(H5N1 surveillance. More important, this study demonstrates the usefulness of influenza genetic surveillance to detect emerging pandemic threat viruses. Conclusions Our study reveals that some countries suffering from human cases of avian influenza have limited participation (e.g. genetic surveillance or data share with global surveillance networks. Also, we demonstrate that the implementation of genetic surveillance programs could increase and strengthen worldwide epidemic and pandemic preparedness. We hope that this work promotes new discussions between policy makers and health

  17. Oseltamivir-resistant influenza A(H1N1pdm09 virus in southern Brazil

    Directory of Open Access Journals (Sweden)

    Camila Marx

    2013-05-01

    Full Text Available The neuraminidase (NA genes of A(H1N1pdm09 influenza virus isolates from 306 infected patients were analysed. The circulation of oseltamivir-resistant viruses in Brazil has not been reported previously. Clinical samples were collected in the state of Rio Grande do Sul (RS from 2009-2011 and two NA inhibitor-resistant mutants were identified, one in 2009 (H275Y and the other in 2011 (S247N. This study revealed a low prevalence of resistant viruses (0.8% with no spread of the resistant mutants throughout RS.

  18. Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005

    NARCIS (Netherlands)

    Adlhoch, C.; Gossner, C.; Koch, G.; Brown, I.; Bouwstra, R.J.; Verdonck, F.; Penttinen, P.; Harder, T.

    2014-01-01

    Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are descri

  19. Melanization and pathogenicity in the insect, Tenebrio molitor, and the crustacean, Pacifastacus leniusculus, by Aeromonas hydrophila AH-3.

    Directory of Open Access Journals (Sweden)

    Chadanat Noonin

    Full Text Available Aeromonas hydrophila is the most common Aeromonas species causing infections in human and other animals such as amphibians, reptiles, fish and crustaceans. Pathogenesis of Aeromonas species have been reported to be associated with virulence factors such as lipopolysaccharides (LPS, bacterial toxins, bacterial secretion systems, flagella, and other surface molecules. Several mutant strains of A. hydrophila AH-3 were initially used to study their virulence in two animal species, Pacifastacus leniusculus (crayfish and Tenebrio molitor larvae (mealworm. The AH-3 strains used in this study have mutations in genes involving the synthesis of flagella, LPS structures, secretion systems, and some other factors, which have been reported to be involved in A. hydrophila pathogenicity. Our study shows that the LPS (O-antigen and external core is the most determinant A. hydrophila AH-3 virulence factor in both animals. Furthermore, we studied the immune responses of these hosts to infection of virulent or non-virulent strains of A. hydrophila AH-3. The AH-3 wild type (WT containing the complete LPS core is highly virulent and this bacterium strongly stimulated the prophenoloxidase activating system resulting in melanization in both crayfish and mealworm. In contrast, the ΔwaaE mutant which has LPS without O-antigen and external core was non-virulent and lost ability to stimulate this system and melanization in these two animals. The high phenoloxidase activity found in WT infected crayfish appears to result from a low expression of pacifastin, a prophenoloxidase activating enzyme inhibitor, and this gene expression was not changed in the ΔwaaE mutant infected animal and consequently phenoloxidase activity was not altered as compared to non-infected animals. Therefore we show that the virulence factors of A. hydrophila are the same regardless whether an insect or a crustacean is infected and the O-antigen and external core is essential for activation of the

  20. Melanization and pathogenicity in the insect, Tenebrio molitor, and the crustacean, Pacifastacus leniusculus, by Aeromonas hydrophila AH-3.

    Science.gov (United States)

    Noonin, Chadanat; Jiravanichpaisal, Pikul; Söderhäll, Irene; Merino, Susana; Tomás, Juan M; Söderhäll, Kenneth

    2010-12-29

    Aeromonas hydrophila is the most common Aeromonas species causing infections in human and other animals such as amphibians, reptiles, fish and crustaceans. Pathogenesis of Aeromonas species have been reported to be associated with virulence factors such as lipopolysaccharides (LPS), bacterial toxins, bacterial secretion systems, flagella, and other surface molecules. Several mutant strains of A. hydrophila AH-3 were initially used to study their virulence in two animal species, Pacifastacus leniusculus (crayfish) and Tenebrio molitor larvae (mealworm). The AH-3 strains used in this study have mutations in genes involving the synthesis of flagella, LPS structures, secretion systems, and some other factors, which have been reported to be involved in A. hydrophila pathogenicity. Our study shows that the LPS (O-antigen and external core) is the most determinant A. hydrophila AH-3 virulence factor in both animals. Furthermore, we studied the immune responses of these hosts to infection of virulent or non-virulent strains of A. hydrophila AH-3. The AH-3 wild type (WT) containing the complete LPS core is highly virulent and this bacterium strongly stimulated the prophenoloxidase activating system resulting in melanization in both crayfish and mealworm. In contrast, the ΔwaaE mutant which has LPS without O-antigen and external core was non-virulent and lost ability to stimulate this system and melanization in these two animals. The high phenoloxidase activity found in WT infected crayfish appears to result from a low expression of pacifastin, a prophenoloxidase activating enzyme inhibitor, and this gene expression was not changed in the ΔwaaE mutant infected animal and consequently phenoloxidase activity was not altered as compared to non-infected animals. Therefore we show that the virulence factors of A. hydrophila are the same regardless whether an insect or a crustacean is infected and the O-antigen and external core is essential for activation of the proPO system

  1. Multiple reassortment events among highly pathogenic avian influenza A(H5N1) viruses detected in Bangladesh.

    Science.gov (United States)

    Gerloff, Nancy A; Khan, Salah Uddin; Balish, Amanda; Shanta, Ireen S; Simpson, Natosha; Berman, Lashondra; Haider, Najmul; Poh, Mee Kian; Islam, Ausraful; Gurley, Emily; Hasnat, Md Abdul; Dey, T; Shu, Bo; Emery, Shannon; Lindstrom, Stephen; Haque, Ainul; Klimov, Alexander; Villanueva, Julie; Rahman, Mahmudur; Azziz-Baumgartner, Eduardo; Ziaur Rahman, Md; Luby, Stephen P; Zeidner, Nord; Donis, Ruben O; Sturm-Ramirez, Katharine; Davis, C Todd

    2014-02-01

    In Bangladesh, little is known about the genomic composition and antigenicity of highly pathogenic avian influenza A(H5N1) viruses, their geographic distribution, temporal patterns, or gene flow within the avian host population. Forty highly pathogenic avian influenza A(H5N1) viruses isolated from humans and poultry in Bangladesh between 2008 and 2012 were analyzed by full genome sequencing and antigenic characterization. The analysis included viruses collected from avian hosts and environmental sampling in live bird markets, backyard poultry flocks, outbreak investigations in wild birds or poultry and from three human cases. Phylogenetic analysis indicated that the ancestors of these viruses reassorted (1) with other gene lineages of the same clade, (2) between different clades and (3) with low pathogenicity avian influenza A virus subtypes. Bayesian estimates of the time of most recent common ancestry, combined with geographic information, provided evidence of probable routes and timelines of virus spread into and out of Bangladesh.

  2. Genetic Characterization of Clade 2.3.2.1 Avian Influenza A(H5N1) Viruses, Indonesia, 2012

    Science.gov (United States)

    Hartawan, Risza; Pudjiatmoko; Wibawa, Hendra; Hardiman; Balish, Amanda; Donis, Ruben; Davis, C. Todd; Samaan, Gina

    2014-01-01

    After reports of unusually high mortality rates among ducks on farms in Java Island, Indonesia, in September 2012, influenza A(H5N1) viruses were detected and characterized. Sequence analyses revealed all genes clustered with contemporary clade 2.3.2.1 viruses, rather than enzootic clade 2.1.3 viruses, indicating the introduction of an exotic H5N1 clade into Indonesia. PMID:24656213

  3. Photometric data analysis of the eclipsing binary system AH Tauri

    CERN Document Server

    El-Sadek, M A; Essam, A; Rassem, M A

    2014-01-01

    Two sets of photometric observations of the system AH Tauri have been analyzed using the latest version of the Wilson-Devinney code. The results show that AH Tauri may classified as A-type of W-UMa eclipsing binary. The mass ratio of q = 0.81, an over-contact degree of f = 0.095, and a slightly temperature difference between the two components have been obtained. The asymmetry of its light curve explained by the presence of a dark spot on the massive component. The physical, geometrical, and absolute parameters have been derived and compared with previous work.

  4. T cells induce extended class II MHC compartments in dendritic cells in a Toll-like receptor-dependent manner.

    Science.gov (United States)

    Boes, Marianne; Bertho, Nicolas; Cerny, Jan; Op den Brouw, Marjolein; Kirchhausen, Tomas; Ploegh, Hidde

    2003-10-15

    Interaction of Ag-loaded dendritic cells with Ag-specific CD4 T cells induces the formation of long tubular class II MHC-positive compartments that polarize toward the T cell. We show involvement of a Toll-like receptor-mediated signal in this unusual form of intracellular class II MHC trafficking. First, wild-type dendritic cells loaded with LPS-free Ag failed to show formation of class II-positive tubules upon Ag-specific T cell engagement, but did so upon supplementation of the Ag with low concentrations of LPS. Second, Ag-loaded myeloid differentiation factor 88 -deficient dendritic cells failed to form these tubules upon interaction with T cells, regardless of the presence of LPS. Finally, inclusion of a cell-permeable peptide that blocks TNFR-associated factor 6 function, downstream of myeloid differentiation factor 88, blocked T cell-dependent tubulation. A Toll-like receptor-dependent signal is thus required to allow Ag-loaded dendritic cells to respond to T cell contact by formation of extended endosomal compartments. This activation does not result in massive translocation of class II MHC molecules to the cell surface.

  5. TOWARDS LOCATING THE NIGERIAN SHARI'AH PENAL CODES ...

    African Journals Online (AJOL)

    Alfa

    State adopted Sharī'ah as its legal system and eleven other states later followed suit. .... He shall pay the blood money where the heirs consent to pardon him iv. .... the heirs remit the death penalty and pardoning for homicide punishable.

  6. Modifications to Optimize the AH-1Z Human Machine Interface

    Science.gov (United States)

    2013-04-18

    The AH-1Z incorporates a Helmet Mounted System Display (HMSD). It consists of the Optimized TopOwl Version II ( OTO V2) helmet and helmet mounted...The OTO HMD display technology relies upon a monochromatic depiction of information in the display color schemes. Providing color to a heads up

  7. Ekonomi Sharî‘ah dan Ketidakadilan Kapitalisme Global

    Directory of Open Access Journals (Sweden)

    MN Harisudin

    2014-01-01

    Full Text Available This paper understands that the Sharî‘ah Economics is a serious contender for the modern global capitalistic economic system. Capitalism has been responsible for the collapse of not only the global economic system but also the moral deterioration of human being. Injustice is the main mark of capitalism. Hence, in a capitalistic society, no law of the game is upheld economically speaking. The strong and the rich rule. The weak is always a victim. This is the main concern of this paper, vis-à-vis which it introduces the Sharî‘ah perspective as providing a good alternative. The paper first speaks of the sources of this “Islamic” system -namely the Qur’an, the Sunna, Ijma and Qiyas- and then delves into its heart, namely justice. The study holds that the main imprint ot Syari’ ah economic system is justice. Being divinely revealed, this system is always in line with the very nature of man as a social being whose responsibility it is to do something beneficial for his fellow human being. Man is not created solely to accumulate wealth, but to serve God, his religion, his community by using wealth among others. Hence, wealth is not the goal, but the means. The goal that every man wants to acquire is happiness. Sharî‘ah Economics–the paper argues- is ordained to provide a practical guideline toward happiness.

  8. CCD Photometric Study and Period Investigation of AH Tauri

    Science.gov (United States)

    Xiang, Fu-Yuan; Xiao, Ting-Yu; Yu, Yun-Xia

    2015-07-01

    In this paper, we present new CCD photometric observations of AH Tauri in the R band observed in 2006 at the Yunnan Observatory. Two new times of light minima were derived from these observations. We modeled the light curves using the 2003 version of the Wilson-Devinney program. The results show that the variations of the light curves can be expained by a cool spot on the primary star. The fill-out factor is about 6.6%, indicating that AH Tauri is a shallow-contact system. The mass ratio was determined to be about 0.505. In addition, the orbital period variations of AH Tauri were investigated based on all of the photoelectric and CCD light minimum times, including our two new data. It was found that the orbital period exhibits a possible periodic variation with a period of {P}{mod}=54.62\\(+/- 0.20) years and a secular period decrease of {dP}/{dt}=-(1.823+/- 0.215)× {10}-7 {days} {{yr}}-1. Since AH Tauri is an overcontact solar-like system, we discuss three mechanisms of the mass transfer, the light-time effect of the third body, and magnetic activity responsible for the orbital period changes.

  9. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    Science.gov (United States)

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  10. PEMIKIRAN ISLAM DALAM PERSPEKTIF SUNNI DAN SYI’AH

    Directory of Open Access Journals (Sweden)

    Muh. Shohibul Itmam

    2013-09-01

    Full Text Available THE ISLAMIC THINKING IN SUNNI AND SYI’AH PERSPECTIVES. This paper attempts to describe the problems associated with Islam in particular with regard to Sunni and Syi’ah teachings. The number of  streams that developed in Islam today has resulted Islam got claims from various clerical community, such as terrorism and others, resulting in the ruination image of  Islam in the constellation of  the religions of  man. As the flow and the teachings of  the most dominating civilization of  the world religions, Sunni and Syiah, including the Wahhabi, are necessary to clarify the existence or clarified the diversity in the constellation of  Islam, considering the number of streams that are currently claiming truth on themselves. Iran as the country becoming a reference in the world of  developing Syi’ah should be used as a reference in the study of  understanding associated with Sunni and Syi’ah. From this country, the world of  Islam knows the concept ofgoverning “Wilayatul Faqih”. The concept was pioneered by the government of Imam Khomeini who became known after Islamic Revolution in Iran 1979 and continues to be developed up to now. Every year Iran is celebrated with a huge demonstration with the slogan in Persian, “Islam Pyruz ast, ast Nabud Istikbar”, Islam is victorious, crushed the vanity of the islam enemy. keywords: Islam, Sunni, Syi’ah, Perspective, Differences, Similarities. Tulisan ini mencoba mengurai persoalan yang berhubungan dengan Islam secara khusus yang berkaitan dengan ajaran Sunni dan Syi’ah. Banyaknya aliran yang berkembang dalam Islam dewasa ini telah mengakibatkan Islam mendapat klaim dari berbagai komunitas agamawan, seperti teroris dan lainnya, yang mengakibatkan redupnya citra Islam dalam percaturan agama-agama manusia. Sebagai aliran dan ajaran yang paling mendominasi peradaban agama dunia, Sunni dan  Syi’ah,  termasuk  Wahabi,  perlu  memperjelas  eksistensinya atau diperjelas

  11. HIV-1 and its gp120 inhibits the influenza A(H1N1pdm09 life cycle in an IFITM3-dependent fashion.

    Directory of Open Access Journals (Sweden)

    Milene Mesquita

    Full Text Available HIV-1-infected patients co-infected with A(H1N1pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1pdm09 life cycle in vitro. We show here that exposure of A(H1N1pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA gene from in vitro experiments and from samples of HIV-1/A(H1N1pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1pdm09 co-infected patients during the recent influenza form 2009/2010.

  12. Isolation of AhDHNs from Arachis hypogaea L. and evaluation of ...

    African Journals Online (AJOL)

    African Journal of Biotechnology. Journal Home ... 100 μM ABA enhanced AhDHNs expression in peanut leaves. When peanut ... AhDHNs expressions increased greatly in peanut leaves treated with 30% polyethylene glycol (PEG). Sodium ...

  13. Elucidation of the Vibrio anguillarum genetic response to the potential fish probiont Pseudomonas fluorescens AH2, using RNA-arbitrarily primed PCR

    DEFF Research Database (Denmark)

    Holmstrøm, Kim; Gram, Lone

    2003-01-01

    with the iron chelator 2,2-dipyridyl. A chromosomal transcript homologous to vibE that participates in vibriobactin synthesis in Vibrio cholerae was also upregulated during AH2 exposure. This transcript could represent a functionally active gene in V. anguillarum involved in biosynthesis of anguibactin......The antagonistic interaction between a potential fish probiont, Pseudomonas fluorescens strain AH2, and its target organism, Vibrio anguillarum, was investigated by studying the genetic response of the target organism when it was exposed to the antagonist. We compared the differential display...

  14. Itraconazole cis-diastereoisomers activate aryl hydrocarbon receptor AhR and pregnane X receptor PXR and induce CYP1A1 in human cell lines and human hepatocytes.

    Science.gov (United States)

    Stepankova, Martina; Pastorkova, Barbora; Bachleda, Petr; Dvorak, Zdenek

    2017-04-05

    Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR. Gene reporter assays showed that itraconazole dose-dependently activated both AhR and PXR, and the activation of AhR but not of PXR was enantiospecific. Itraconazole diastereoisomers transformed AhR and PXR into their DNA-binding forms, as demonstrated by electromobility shift assays. Cytochrome P450 CYP1A1 mRNA and protein were induced by itraconazole diastereoisomers in human hepatoma cells HepG2, human skin cells HaCaT, and in primary human hepatocytes. The expression of CYP3A4 in human intestinal LS180 cells was not influenced by itraconazole, but we observed downregulation of CYP3A4 in human hepatocytes. Collectively, we show that itraconazole is a dual activator of AhR and PXR, with differential effects on the target genes for xenoreceptors. The enantiospecific pattern was observed only in gene reporter assays for AhR. The data presented here might be of toxicological and clinical importance.

  15. Overexpression of Grain Amaranth (Amaranthus hypochondriacus) AhERF or AhDOF Transcription Factors in Arabidopsis thaliana Increases Water Deficit- and Salt-Stress Tolerance, Respectively, via Contrasting Stress-Amelioration Mechanisms

    Science.gov (United States)

    Massange-Sánchez, Julio A.; Palmeros-Suárez, Paola A.; Espitia-Rangel, Eduardo; Rodríguez-Arévalo, Isaac; Sánchez-Segura, Lino; Martínez-Gallardo, Norma A.; Alatorre-Cobos, Fulgencio; Tiessen, Axel; Délano-Frier, John P.

    2016-01-01

    Two grain amaranth transcription factor (TF) genes were overexpressed in Arabidopsis plants. The first, coding for a group VII ethylene response factor TF (i.e., AhERF-VII) conferred tolerance to water-deficit stress (WS) in transgenic Arabidopsis without affecting vegetative or reproductive growth. A significantly lower water-loss rate in detached leaves coupled to a reduced stomatal opening in leaves of plants subjected to WS was associated with this trait. WS tolerance was also associated with an increased antioxidant enzyme activity and the accumulation of putative stress-related secondary metabolites. However, microarray and GO data did not indicate an obvious correlation between WS tolerance, stomatal closure, and abscisic acid (ABA)-related signaling. This scenario suggested that stomatal closure during WS in these plants involved ABA-independent mechanisms, possibly involving reactive oxygen species (ROS). WS tolerance may have also involved other protective processes, such as those employed for methyl glyoxal detoxification. The second, coding for a class A and cluster I DNA binding with one finger TF (i.e., AhDof-AI) provided salt-stress (SS) tolerance with no evident fitness penalties. The lack of an obvious development-related phenotype contrasted with microarray and GO data showing an enrichment of categories and genes related to developmental processes, particularly flowering. SS tolerance also correlated with increased superoxide dismutase activity but not with augmented stomatal closure. Additionally, microarray and GO data indicated that, contrary to AhERF-VII, SS tolerance conferred by AhDof-AI in Arabidopsis involved ABA-dependent and ABA-independent stress amelioration mechanisms. PMID:27749893

  16. The inhibition of lung cancer cell migration by AhR-regulated autophagy

    Science.gov (United States)

    Tsai, Chi-Hao; Li, Ching-Hao; Cheng, Yu-Wen; Lee, Chen-Chen; Liao, Po-Lin; Lin, Cheng-Hui; Huang, Shih-Hsuan; Kang, Jaw-Jou

    2017-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in multiple organs and tissues. Whereas AhR mediates the metabolism of xenobiotic and endogenous compounds, its novel function in cancer epithelial-mesenchymal transition (EMT) remains controversial. Autophagy also participates in tumour progression through its functions in cell homeostasis and facilitates adaptation to EMT progression. In the present study, we found that AhR-regulated autophagy positively modulates EMT in non-small cell lung cancer cells. The motility of A549, H1299, and CL1-5 cells were correlated with different AhR expression levels. Invasive potential and cell morphology also changed when AhR protein expression was altered. Moreover, AhR levels exerted a contrasting effect on autophagy potential. Autophagy was higher in CL1-5 and H1299 cells with lower AhR levels than in A549 cells. Both AhR overexpression and autophagy inhibition decreased CL1-5 metastasis in vivo. Furthermore, AhR promoted BNIP3 ubiquitination for proteasomal degradation. AhR silencing in A549 cells also reduced BNIP3 ubiquitination. Taken together, these results provide a novel insight into the cross-linking between AhR and autophagy, we addressed the mechanistic BNIP3 modulation by endogenous AhR, which affect cancer cell EMT progression. PMID:28195146

  17. Guiding outbreak management by the use of influenza A(H7Nx) virus sequence analysis

    NARCIS (Netherlands)

    Jonges, M.; Meijer, A.; Fouchier, R.A.M.; Koch, G.; Li, J.; Pan, J.C.; Shu, Y.L.; Koopmans, M.P.G.; Chen, H.

    2013-01-01

    The recently identified human infections with avian influenza A(H7N9) viruses in China raise important questions regarding possible source and risk to humans. Sequence comparison with an influenza A(H7N7) outbreak in the Netherlands in 2003 and an A(H7N1) epidemic in Italy in 1999–2000 suggests that

  18. Guiding outbreak management by the use of influenza a(H7NX) virus sequence analysis

    NARCIS (Netherlands)

    M. Jonges (Marcel); A. Meijer (Adam); R.A.M. Fouchier (Ron); G. Koch (Guus); J. Li; J.C. Pan; H. Chen (Hong); Y.L. Shu (Yue-Long); M.P.G. Koopmans D.V.M. (Marion)

    2013-01-01

    textabstractThe recently identified human infections with avian influenza A(H7N9) viruses in China raise important questions regarding possible source and risk to humans. Sequence comparison with an influenza A(H7N7) outbreak in the Netherlands in 2003 and an A(H7N1) epidemic in Italy in 1999-2000 s

  19. Possible role of songbirds and parakeets in transmission of influenza A(H7N9) virus to humans.

    Science.gov (United States)

    Jones, Jeremy C; Sonnberg, Stephanie; Koçer, Zeynep A; Shanmuganatham, Karthik; Seiler, Patrick; Shu, Yuelong; Zhu, Huachen; Guan, Yi; Peiris, Malik; Webby, Richard J; Webster, Robert G

    2014-03-01

    Avian-origin influenza A(H7N9) recently emerged in China, causing severe human disease. Several subtype H7N9 isolates contain influenza genes previously identified in viruses from finch-like birds. Because wild and domestic songbirds interact with humans and poultry, we investigated the susceptibility and transmissibility of subtype H7N9 in these species. Finches, sparrows, and parakeets supported replication of a human subtype H7N9 isolate, shed high titers through the oropharyngeal route, and showed few disease signs. Virus was shed into water troughs, and several contact animals seroconverted, although they shed little virus. Our study demonstrates that a human isolate can replicate in and be shed by such songbirds and parakeets into their environment. This finding has implications for these birds' potential as intermediate hosts with the ability to facilitate transmission and dissemination of A(H7N9) virus.

  20. Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

    Directory of Open Access Journals (Sweden)

    Esposito Susanna

    2010-08-01

    Full Text Available Abstract A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6% and in all 17 samples (100%; p

  1. Detection of avian influenza A/H7N9/2013 virus by real-time reverse transcription-polymerase chain reaction.

    Science.gov (United States)

    Kang, Xiaoping; Wu, Weili; Zhang, Chuntao; Liu, Licheng; Feng, Huahua; Xu, Lizhi; Zheng, Xin; Yang, Honglei; Jiang, Yongqiang; Xu, Bianli; Xu, Jin; Yang, Yinhui; Chen, Weijun

    2014-09-01

    The first case of avian influenza A/H7N9 infection was reported in Shanghai in mid-February, 2013; by May 1, 2013, it had infected 127 people and caused 26 deaths in 10 provinces in China. Therefore, it is important to obtain reliable epidemiological data on the spread of this new infectious agent, a need that may be best met by the development of novel molecular methods. Here, a new method was described for the detection of avian influenza A/H7N9 using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Using serial dilutions of avian influenza A H7N9 cultures, the detection limit of the assay was determined to be approximately 3.2×10(-4) HAUs (hemagglutination units) for the H7 gene and 6.4×10(-4) HAUs for N9 gene. In tests of serial dilutions of in vitro-transcribed avian influenza A H7 and N9 gene RNA, positive results were obtained for target RNA containing at least three copies of the H7 gene and six copies of the N9 gene. Thirteen throat swabs from H7N9 patients were tested; all tested positive in the assay. Specificity was evaluated by testing 18 other subtypes of influenza viruses; all tested negative. A total of 180 throat swabs from patients infected with influenza virus, including 60 from patients infected with seasonal influenza A/H1N1 virus, 60 from patients infected with pandemic influenza A/H1N1/2009 virus, 30 from patients infected with seasonal influenza A/H3N2 virus and 30 from patients infected with influenza B virus, were also tested; all tested negative.

  2. The progress of research on influenza A(H1N1)%甲型H1N1流感的研究进展

    Institute of Scientific and Technical Information of China (English)

    雷晓燕; 孙永红

    2010-01-01

    Influenza A(H1N1)virus is a re-mixed strains of human influenza virus genes,avian influenza virus gene and swine influenza virus gene.Influenza A(H1N1)pandemic influenza has spread around the world,which has drawn worldwide attention.In order to early discovery,early diagnosis,early treatment and effective prevention of Influenza A(H1N1),we describe the characteristics of linfluenza A(H1N1)virus,epidemiology,pathogenesis,clinical manifestations,laboratory examination and effective treatment and preventive measures.%甲型H1N1流感病毒是人流感病毒基因、禽流感病毒基因和猪流感病毒基因混合的重配株,其造成的疫情来势凶猛,引起世界各国的广泛关注.为了早发现、早诊断、早治疗及有效地预防甲型H1N1流感,本文综述了甲型H1N1流感病毒的特点、流行病学、致人发病的机制、甲型H1N1流感患者的临床表现、实验室检查及有效的治疗和预防措施.

  3. Phylogeography of Influenza A(H3N2) Virus in Peru, 2010–2012

    Science.gov (United States)

    Nelson, Martha I.; Kasper, Matthew; Tinoco, Yeny; Simons, Mark; Romero, Candice; Silva, Marita; Lin, Xudong; Halpin, Rebecca A.; Fedorova, Nadia; Stockwell, Timothy B.; Wentworth, David; Holmes, Edward C.; Bausch, Daniel G.

    2015-01-01

    It remains unclear whether lineages of influenza A(H3N2) virus can persist in the tropics and seed temperate areas. We used viral gene sequence data sampled from Peru to test this source–sink model for a Latin American country. Viruses were obtained during 2010–2012 from influenza surveillance cohorts in Cusco, Tumbes, Puerto Maldonado, and Lima. Specimens positive for influenza A(H3N2) virus were randomly selected and underwent hemagglutinin sequencing and phylogeographic analyses. Analysis of 389 hemagglutinin sequences from Peru and 2,192 global sequences demonstrated interseasonal extinction of Peruvian lineages. Extensive mixing occurred with global clades, but some spatial structure was observed at all sites; this structure was weakest in Lima and Puerto Maldonado, indicating that these locations may experience greater viral traffic. The broad diversity and co-circulation of many simultaneous lineages of H3N2 virus in Peru suggests that this country should not be overlooked as a potential source for novel pandemic strains. PMID:26196599

  4. Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

    Science.gov (United States)

    Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

    2014-12-18

    Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

  5. 过表达转录因子 AhAREB1对拟南芥生长素分布的影响%Auxin Distribution in Arabidopsis Plants Over-Expressing AhAREB1 Encoding a Transcription Factor

    Institute of Scientific and Technical Information of China (English)

    林莹莹; 李晓云; 刘帅; 钟钰婷; 李玲

    2015-01-01

    本课题组前期研究表明,过表达AhAREB1(花生AREB转录因子基因)植株矮小,叶片卷曲,抗旱能力增强,体内IAA含量升高,推测AhAREB1可能影响植株体内IAA分布。该文采用携带3个重复IAA化学诱导启动子元件的pDR5:GUS植株与AhAREB1过表达拟南芥植株的杂交纯合后代,通过GUS组织化学染色方法,探讨AhAREB1转录因子对植株体内IAA分布的影响。结果表明,过表达AhAREB1植株体内IAA增加,主要分布在幼苗的根尖和成苗的叶片边缘;在过表达植株IAA响应基因IAA29和IAA运输蛋白基因LAX3表达均显著下调,而IAA响应蛋白基因ARF2和ARF9显著上调。过表达AhAREB1植株体内IAA分布不均衡是引起表型变化的原因之一。%Our previous study showed that Arabidopsis plants over-expressing AhAREB1 ( a peanut AREB transcrip-tion factor) displayed growth retardation, curly leaves, enhanced drought tolerance and increased IAA content.It is implied that auxin distribution may be affected by the expression of AhAREB1.In the present study, the homozy-gous transgenic Arabidopsis, generated by hybridizing the pDR5::GUS ( harboring GUS gene driven by a promoter with three repeat IAA-induced elements) plants with AhAREB1 over-expressing plants, was used to further investi-gate the effect of the expression of AhAREB1 transcription factor on auxin distribution through GUS histochemical staining .The results showed that the IAA content was increased in AhAREB1 over-expressing plants when compared with that in the controlled plants.The IAA mainly accumulated in the root tip of transgenic seedlings, instead on the edge of the leaves in mature plants.The expressions of IAA-responsive genes IAA29 and IAA-transport gene LAX3 in AhAREB1 over-expressing plants were significantly down-regulated, whereas The expressions of other two IAA-responsive genes ARF2 and ARF9 were significantly up-regulated.Take together, the unbalanced IAA distri

  6. PERKEMBANGAN HOTEL SYARI’AH DI INDONESIA; MENGONSEP PARIWISATA ISLAMI

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    Fahruddin Ali Sabri

    2012-05-01

    Full Text Available Fahruddin Ali Sabri (Penulis, dosen STAIN Pamekasan, Jl. Raya Panglegur Km. 04 Pamekasan. Kontak 08521346464, e-mail didin021@yahoo.com     Abstract Indonesian tourism sector has been developed rapidly and significantly. Hotels sector high income contribution indicates the significant development, so it influences public prosperity. Syari’ah Hotel is one of the hotel models offering certain facilities that matches Islamic values.  Its  development opens promising market chance that must be grounded on non-alcohol, drug-abused free and adultery prohibition concept. It facilitates the guests to have comfortable and safe stay. Kata-kata kunci Hotel, Pariwisata dan Syarî’ah

  7. Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.

    Directory of Open Access Journals (Sweden)

    Judith M Fonville

    Full Text Available Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.

  8. Characterization of the transgenic CA-AhR mouse - cell specific expression of the CA-AhR using CYP1A1 as a marker

    Energy Technology Data Exchange (ETDEWEB)

    Brunnberg, S.; Lindstam, M.; Andersson, P.; Hanberg, A. [Institute of Environmental Medicine, Stockholm (Sweden); Poellinger, L. [Department of Cell and Molecular Biology, Stockholm (Sweden)

    2004-09-15

    The risk assessments of dioxins and dioxin-like PCBs performed by WHO and EU lead to major concerns. The tolerable daily intake for humans has been assessed to be within the range of human exposures occurring in the general population today. Dioxins are known to adversely impair reproduction and affect development of reproductive organs, as well as the early development of the immune and the nervous systems. The Aryl hydrocarbon Receptor (AhR) mediates most toxic effects of dioxins, such as 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and PCBs. In order to study the mechanisms of 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 most (or all) organs. Consequently, the CA-AhR mice show several of the well-known effects of dioxin exposure. Since the CA-AhR is continuously active at a relatively low level and from early development, this model resembles the human exposure scenario and is thus suitable for studies on mechanisms of action of Ah receptor ligands.

  9. Development of influenza A(H7N9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs

    Science.gov (United States)

    Ridenour, Callie; Johnson, Adam; Winne, Emily; Hossain, Jaber; Mateu-Petit, Guaniri; Balish, Amanda; Santana, Wanda; Kim, Taejoong; Davis, Charles; Cox, Nancy J; Barr, John R; Donis, Ruben O; Villanueva, Julie; Williams, Tracie L; Chen, Li-Mei

    2015-01-01

    Background The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation. Methods Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera. Results Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a twofold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage. However, HI tests indicated that the antigenic properties of two CVVs remained unchanged. Conclusions If influenza A(H7N9) viruses were to acquire sustained human-to-human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation. PMID:25962412

  10. Continued dominance of pandemic A(H1N1 2009 influenza in Victoria, Australia in 2010

    Directory of Open Access Journals (Sweden)

    James E. Fielding

    2011-08-01

    Full Text Available The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95% were influenza A infections - 1001 (55% pandemic A(H1N1 2009, 4 (<1% A(H3N2 and 807 (45% not subtyped; 88 (5% were influenza B; and 14 (< 1% were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9% were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene.

  11. Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site.

    Science.gov (United States)

    Mögling, Ramona; Richard, Mathilde J; Vliet, Stefan van der; Beek, Ruud van; Schrauwen, Eefje J A; Spronken, Monique I; Rimmelzwaan, Guus F; Fouchier, Ron A M

    2017-06-01

    Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin. Using representative virus recombinants it was shown that the haemagglutinin of a recent A(H3N2) virus indeed had decreased activity to agglutinate turkey erythrocytes, while its neuraminidase displayed increased haemagglutinating activity. Viruses with chimeric and mutant neuraminidases were used to identify the amino acid substitution histidine to arginine at position 150 flanking the neuraminidase catalytic site as the determinant of this neuraminidase-mediated haemagglutination. An analysis of publicly available neuraminidase gene sequences showed that viruses with histidine at position 150 were rapidly replaced by viruses with arginine at this position between 2005 and 2008, in agreement with the phenotypic data. As a consequence of neuraminidase-mediated haemagglutination of recent A(H3N2) viruses and poor haemagglutination via haemagglutinin, haemagglutination inhibition assays with A(H3N2) antisera are no longer useful to characterize the antigenic properties of the haemagglutinin of these viruses for vaccine strain selection purposes. Continuous monitoring of the evolution of these viruses and potential consequences for vaccine strain selection remains important.

  12. Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010-2011 in Spain.

    Science.gov (United States)

    Ledesma, Juan; Pozo, Francisco; Reina, Gabriel; Blasco, Miriam; Rodríguez, Guadalupe; Montes, Milagrosa; López-Miragaya, Isabel; Salvador, Carmen; Reina, Jordi; Ortíz de Lejarazu, Raúl; Egido, Pilar; López Barba, José; Delgado, Concepción; Cuevas, María Teresa; Casas, Inmaculada

    2012-01-01

    Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010-2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Andrysik, Zdenek [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Vondracek, Jan [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic) and Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic)]. E-mail: vondracek@ibp.cz; Machala, Miroslav [Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Krcmar, Pavel [Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Svihalkova-Sindlerova, Lenka [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Kranz, Anne [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Weiss, Carsten [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Faust, Dagmar [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Kozubik, Alois [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Dietrich, Cornelia [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany)

    2007-02-03

    Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their effects were significantly reduced in cells expressing a dominant-negative AhR mutant (dnAhR). Roscovitine, a chemical inhibitor of cdk2, abolished the induction of cell proliferation by BbF. However, neither BaA nor BbF modulated expression of the principal cdk inhibitor involved in maintenance of contact inhibition, p27{sup Kip1}, or pRb phosphorylation. The strongly mutagenic BaP induced apoptosis, a decrease in total cell numbers and significantly higher percentage of cells entering S-phase than either BaA or BbF. Given that BaP induced high levels of Cyclin A/cdk2 activity, downregulation of p27{sup Kip1} and hyperphosphorylation of pRb, the accumulation of cells in S-phase was probably due to cell proliferation, although S-phase arrest due to blocked replication forks can not be excluded. Both types of effects of BaP were significantly attenuated in dnAhR cells. Transfection of WB-F344 cells with siRNA targeted against AhR decreased induction of Cyclin A induced by BbF or BaP, further supporting the role of AhR in proliferative effects of PAHs. This suggest that activation of AhR plays a significant role both in disruption of contact inhibition by weakly mutagenic PAHs and in genotoxic effects of BaP possibly leading to enhanced cell proliferation. Thus, PAHs may

  14. Oxysterol generation and liver X receptor-dependent reverse cholesterol transport: not all roads lead to Rome.

    Science.gov (United States)

    Pannu, Parveer S; Allahverdian, Sima; Francis, Gordon A

    2013-04-10

    Cell cholesterol metabolism is a tightly regulated process, dependent in part on activation of nuclear liver X receptors (LXRs) to increase expression of genes mediating removal of excess cholesterol from cells in the reverse cholesterol transport pathway. LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles. Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol-27-hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR-dependent gene activation. This block does not appear to be compensated by oxysterol production in other cell compartments. The purpose of this review is to summarize current knowledge about oxysterol-dependent activation by LXR of genes involved in reverse cholesterol transport, and what these defects of cell cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR-dependent genes.

  15. Calorimetry of 25 Ah lithium/thionyl chloride cells

    Science.gov (United States)

    Johnson, C. J.; Dawson, S.

    1991-01-01

    Heat flow measurements of 25-Ah lithium thionyl chloride cells provided a method to calculate an effective thermal potential, E(TP) of 3.907 V. The calculation is useful to determine specific heat generation of this cell chemistry and design. The E(TP) value includes heat generation by electrochemical cell reactions, competitive chemical reactions, and resistance heating at the tabs, connectors, and leads. Heat flow was measured while applying electrical loads to the cell in an isothermal calorimeter set at 0, 20, and 60 C.

  16. Calorimetry of 25 Ah lithium/thionyl chloride cells

    Science.gov (United States)

    Johnson, C. J.; Dawson, S.

    1991-01-01

    Heat flow measurements of 25-Ah lithium thionyl chloride cells provided a method to calculate an effective thermal potential, E(TP) of 3.907 V. The calculation is useful to determine specific heat generation of this cell chemistry and design. The E(TP) value includes heat generation by electrochemical cell reactions, competitive chemical reactions, and resistance heating at the tabs, connectors, and leads. Heat flow was measured while applying electrical loads to the cell in an isothermal calorimeter set at 0, 20, and 60 C.

  17. Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit.

    Science.gov (United States)

    Zhang, YiMin; Liu, JiMin; Yu, Liang; Zhou, Ning; Ding, Wei; Zheng, ShuFa; Shi, Ding; Li, LanJuan

    2016-01-06

    Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%-2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.

  18. Human infection with avian influenza A(H7N9) virus re-emerges in China in winter 2013.

    Science.gov (United States)

    Chen, E; Chen, Y; Fu, L; Chen, Z; Gong, Z; Mao, H; Wang, D; Ni, M Y; Wu, P; Yu, Z; He, T; Li, Z; Gao, J; Liu, S; Shu, Y; Cowling, B J; Xia, S; Yu, H

    2013-10-24

    Through a national surveillance system for unexplained pneumonia, a severe case of influenza A(H7N9) in a man in his mid-30s was identified in Zhejiang Province, China on 14 October 2013. Epidemiological and clinical findings were consistent with the patterns reported during the outbreak in spring 2013, and laboratory findings showed that the virus had 99.6% identity with earlier H7N9 viruses identified in humans in the spring except for five mutations in the NA gene.

  19. AH-64 IHADSS aviator vision experiences in Operation Iraqi Freedom

    Science.gov (United States)

    Hiatt, Keith L.; Rash, Clarence E.; Harris, Eric S.; McGilberry, William H.

    2004-09-01

    Forty AH-64 Apache aviators representing a total of 8564 flight hours and 2260 combat hours during Operation Iraqi Freedom and its aftermath were surveyed for their visual experiences with the AH-64's monocular Integrated Helmet and Display Sighting System (IHADSS) helmet-mounted display in a combat environment. A major objective of this study was to determine if the frequencies of reports of visual complaints and illusions reported in the previous studies, addressing mostly benign training environments, differ in the more stressful combat environments. The most frequently reported visual complaints, both while and after flying, were visual discomfort and headache, which is consistent with previous studies. Frequencies of complaints after flying in the current study were numerically lower for all complaint types, but differences from previous studies are statistically significant only for visual discomfort and disorientation (vertigo). With the exception of "brownout/whiteout," reports of degraded visual cues in the current study were numerically lower for all types, but statistically significant only for impaired depth perception, decreased field of view, and inadvertent instrumental meteorological conditions. This study also found statistically lower reports of all static and dynamic illusions (with one exception, disorientation). This important finding is attributed to the generally flat and featureless geography present in a large portion of the Iraqi theater and to the shift in the way that the aviators use the two disparate visual inputs presented by the IHADSS monocular design (i.e., greater use of both eyes as opposed to concentrating primarily on display imagery).

  20. Structural Insights into the Association of Hif1 with Histones H2A-H2B Dimer and H3-H4 Tetramer.

    Science.gov (United States)

    Zhang, Mengying; Liu, Hejun; Gao, Yongxiang; Zhu, Zhongliang; Chen, Zijun; Zheng, Peiyi; Xue, Lu; Li, Jixi; Teng, Maikun; Niu, Liwen

    2016-10-04

    Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  2. Recombinant equine herpesvirus 1 (EHV-1) vaccine protects pigs against challenge with influenza A(H1N1)pmd09.

    Science.gov (United States)

    Said, Abdelrahman; Lange, Elke; Beer, Martin; Damiani, Armando; Osterrieder, Nikolaus

    2013-05-01

    Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs but also a threat to human health. The pandemic influenza A(H1N1)pdm09 virus likely originated in swine through reassortment between a North American triple reassortant and Eurasian avian-like SIV. The North American triple reassortant virus harbors genes from avian, human and swine influenza viruses. An effective vaccine may protect the pork industry from economic losses and curb the development of new virus variants that may threaten public health. In the present study, we evaluated the efficacy of a recombinant equine herpesvirus type 1 (EHV-1) vaccine (rH_H1) expressing the hemagglutinin H1 of A(H1N1)pdm09 in the natural host. Our data shows that the engineered rH_H1 vaccine induces influenza virus-specific antibody responses in pigs and is able to protect at least partially against challenge infection: no clinical signs of disease were detected and virus replication was reduced as evidenced by decreased nasal virus shedding and faster virus clearance. Taken together, our results indicate that recombinant EHV-1 encoding H1 of A(H1N1)pdm09 may be a promising alternative for protection of pigs against infection with A(H1N1)pdm09 or other influenza viruses.

  3. Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections.

    Science.gov (United States)

    Horm, Srey Viseth; Tarantola, Arnaud; Rith, Sareth; Ly, Sowath; Gambaretti, Juliette; Duong, Veasna; Y, Phalla; Sorn, San; Holl, Davun; Allal, Lotfi; Kalpravidh, Wantanee; Dussart, Philippe; Horwood, Paul F; Buchy, Philippe

    2016-07-20

    Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.

  4. Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation.

    Science.gov (United States)

    Metzger, Eric; Willmann, Dominica; McMillan, Joel; Forne, Ignasi; Metzger, Philipp; Gerhardt, Stefan; Petroll, Kerstin; von Maessenhausen, Anne; Urban, Sylvia; Schott, Anne-Kathrin; Espejo, Alexsandra; Eberlin, Adrien; Wohlwend, Daniel; Schüle, Katrin M; Schleicher, Michael; Perner, Sven; Bedford, Mark T; Jung, Manfred; Dengjel, Jörn; Flaig, Ralf; Imhof, Axel; Einsle, Oliver; Schüle, Roland

    2016-02-01

    Prostate cancer evolution is driven by a combination of epigenetic and genetic alterations such as coordinated chromosomal rearrangements, termed chromoplexy. TMPRSS2-ERG gene fusions found in human prostate tumors are a hallmark of chromoplexy. TMPRSS2-ERG fusions have been linked to androgen signaling and depend on androgen receptor (AR)-coupled gene transcription. Here, we show that dimethylation of KDM1A at K114 (to form K114me2) by the histone methyltransferase EHMT2 is a key event controlling androgen-dependent gene transcription and TMPRSS2-ERG fusion. We identified CHD1 as a KDM1A K114me2 reader and characterized the KDM1A K114me2-CHD1 recognition mode by solving the cocrystal structure. Genome-wide analyses revealed chromatin colocalization of KDM1A K114me2, CHD1 and AR in prostate tumor cells. Together, our data link the assembly of methylated KDM1A and CHD1 with AR-dependent transcription and genomic translocations, thereby providing mechanistic insight into the formation of TMPRSS2-ERG gene fusions during prostate-tumor evolution.

  5. Highly Pathogenic Reassortant Avian Influenza A(H5N1) Virus Clade 2.3.2.1a in Poultry, Bhutan

    Science.gov (United States)

    Marinova-Petkova, Atanaska; Franks, John; Tenzin, Sangay; Dahal, Narapati; Dukpa, Kinzang; Dorjee, Jambay; Feeroz, Mohammed M.; Rehg, Jerold E.; Barman, Subrata; Krauss, Scott; McKenzie, Pamela; Webby, Richard J.

    2016-01-01

    Highly pathogenic avian influenza A(H5N1), clade 2.3.2.1a, with an H9-like polymerase basic protein 1 gene, isolated in Bhutan in 2012, replicated faster in vitro than its H5N1 parental genotype and was transmitted more efficiently in a chicken model. These properties likely help limit/eradicate outbreaks, combined with strict control measures. PMID:27584733

  6. Revisiting Shari’ah, democracy and human rights in Nigeria

    Directory of Open Access Journals (Sweden)

    Williams O. Mbamalu

    2012-11-01

    Full Text Available This article argued that in a pluralistic and complex society such as Nigeria the invocation of Shari’ah (Islamic law does not augur well for the survival of democracy. The traditional belief of every Muslim is that fundamentalism has been and must continue to be rooted in the concept of theocracy upon which the medieval institution of the Caliphate actually rested. Muslim political leaders challenge the agitation for a secular state in Nigeria as an inspiration by Christian theology based on Western European thought. This article argued that political and social progress in Nigeria is unrealistic without the separation of religion and politics. It was identified in this article that the separation of religion and politics does not go down well with Islamic eschatology and cosmology, because Islam’s main theological drive is toward an Islamic world empire. The solution offered in this article was that emphasis should be on ensuring that any legal framework or constitutional arrangement should be one that safeguards the interests of all citizens.’n Blik op Shari’ah, demokrasie en menseregte in Nigerië. Hierdie artikel argumenteer dat, in ’n pluralistiese en komplekse samelewing soos Nigerië, die aanroeping van Shari’ah (Islamitiese wet niks goeds voorspel vir die oorlewing van die demokrasie is nie. Die radisionele geloof van elke Moslem is dat fundamentalisme in die konsep van teokrasie, wat sy oorsprong in die  Middeleeuse instelling van die Kalifaat het, gewortel is en so moet bly. Politieke Moslemleiers beskuldig die Christelike teologie (wat op die Wes-Europese gedagte gebaseer is as die oorsaak van die onrus as gevolg van die poging om ‘n sekulere staat in Nigerie tot stand te bring. In hierdie artikel is is ook geargumenteer dat politieke en sosiale vooruitgang in Nigerië nie moontlik is sonder die skeiding van godsdiens en politiek nie. Daar is ook bevind dat die skeiding tussen godsdiens en politiek nie by die

  7. ASURANSI SYARI’AH ANTARA AJARAN SYARA’ DAN PEMBENARAN BUDAYA

    Directory of Open Access Journals (Sweden)

    Nur Aziz Muslim

    2005-09-01

    Full Text Available Abstrak: Islam sebagai agama universal harus tampil elegan dalam mengurai permasalahan kehidupan manusia. Meskipun ia hadir sebagai blue print dari Tuhan, kehadirannya tidak bisa lepas dari budaya. Meskipun kehadiran budaya sebagai sesuatu yang berada di luar blue print Tuhan, keberadaan budaya kerap kali memengaruhi diundangkannya suatu ketentuan hukum Dalam masalah mu’âmalah (ekonomi syari’ah misalnya, asuransi yang merupakan hasil karya manusia harus direspon secara positif karena tidak ada larangan terhadapnya dan ia sejalan dengan prinsip universal ajaran  Islam, yakni saling menolong, saling melindungi, dan saling menanggung. Karena itu, memasukkan asuransi sebagai entry dalam ensiklopedi Islam merupakan keharusan, karena dalam Islam adat juga dapat digunakan sebagai sumber hukum Islam. Pertimbangan ini dikuatkan dengan adanya kemaslahatan yang ada di dalam asuransi itu sendiri bagi umat Islam. Meskipun tidak bisa dipungkiri adanya tarik ulur tentang halal atau tidaknya asuransi masih mewarnai ijtihad para ulama yang mempunyai otoritas tentang masalah itu, namun seyogyanya yang perlu dipertimbangkan juga adalah adanya sentimen positif dari masyarakat tentang keberadaan asuransi syari’ah dengan pertumbuhannya dari tahun ketahun yang menunjukkan pertumbuhan yang sangat fantastis. Abstract: As a universal religion, Islam should appears elegantly in describing social problems. Islam as a norms are the blue print of God, however, its implementation is not free from the influence of culture, as the out sider of God blue print. Culture often influences the enactment of Islamic legal provision. In case of mu’âmalah (Islamic economy, insurance for instant, is a man made system of economy that should be regarded positively since there is no prohibition on it  and it is in accordance with the universal Islamic teaching; helping each other, guarding one another and taking risk together. Therefore, taking it as an entry in Islamic

  8. An Exploratory Study of the Rhetoric in CSR Reports: A Comparison of Shari’ah Compliant Company and Non –Shari’ah Compliant Company in Malaysia

    OpenAIRE

    Abdul Razak Rafizan

    2017-01-01

    This paper advances previous research in corporate social reporting (CSR) by using a taxonomy of five distinct rhetorical strategies to examine any differences in term of type of ethical categories and to identify moral attitudes towards different societal activities between Shari’ah compliant company Bank Islam Malaysia Berhad (BIMB) and Non-Shari’ah compliant company Malayan Banking Berhad (Maybank). The data is analyzed using content analysis. The findings revealed that there are different...

  9. Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures

    Science.gov (United States)

    Chattopadhyay, Indranil; Wang, Jianmin; Qin, Maochun; Gao, Lingqiu; Holtz, Renae; Vessella, Robert L.; Leach, Robert W.; Gelman, Irwin H.

    2017-01-01

    Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells. Src induces additional gene signatures unique to CRPC cell lines, LNCaP-C4-2 and CWR22Rv1, and to CRPC LuCaP35.1 xenografts. By comparing the Src-induced AR-cistrome and/or transcriptome in LNCaP to those in CRPC and LuCaP35.1 tumors, we identified an 11-gene Src-regulated CRPC signature consisting of AR-dependent, AR binding site (ARBS)-associated genes whose expression is altered by DHT in LNCaP[Src527F] but not in LNCaP cells. The differential expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival, with the expression of BCAT1 required for Src-induced androgen-independent proliferation. Lastly, Src enhances AR binding to non-canonical ARBS enriched for FOXO1, TOP2B and ZNF217 binding motifs; cooperative AR/TOP2B binding to a non-canonical ARBS was both Src- and DHT-sensitive and correlated with increased levels of Src-induced phosphotyrosyl-TOP2B. These data suggest that CRPC progression is facilitated via Src-induced sensitization of AR to intracrine androgen levels, resulting in the engagement of canonical and non-canonical ARBS-dependent gene signatures. PMID:28055971

  10. HUBUNGAN HUKUM KEMITRAAN DALAM LINKAGE PROGRAM PERBANKAN SYARI’AH

    Directory of Open Access Journals (Sweden)

    Johan Arifin

    2016-05-01

    Full Text Available Linkage program is a strategy that aims to empower and provide access to capital for small and medium enterprises (UMKM through the involvement of participation in the financial industry. It is based on the fact that BPR/S or Shari'ah microfinance institutions like Baitul Maal Wa Tamwil (BMT sometimes have problems in mobilizing public sector funds. While commercial banks on the other hand tend to have excess funds that the public sector (over liquidity but space is limited to micro business reach its movement.In other words, that the benefits of this program, commercial banks have easy access to UMKM and BMT benefit from the availability of funds to be distributed to the debtor, with due regard to the risk management process so as not to encourage an increase in the ratio of financing problems (non-performing financing.

  11. Molecular cloning and characterization of a cDNA encoding a laminin-binding protein (AhLBP) from Acanthamoeba healyi.

    Science.gov (United States)

    Hong, Yeon-Chul; Lee, Won-Myung; Kong, Hyun-Hee; Jeong, Hae-Jin; Chung, Dong-Il

    2004-01-01

    Adherence of Acanthamoeba to host tissue is believed to be crucial in the establishment of amoebic keratitis or GAE. We have isolated a cDNA from a GAE-causing gymnoamoeba, Acanthamoeba healyi, encoding a protein that binds laminin by screening with a peptide G-specific DNA probe. The cDNA clone (AhLBP) was identified on the basis of sequence homology to the nonintegrin mammalian metastasis-associated 67-kDa laminin receptor (67-LR). The predicted amino acid sequence is 256 residues long with a calculated molecular mass of 28.2kDa and a theoretical pI of 5.48. Southern and Northern blot analyses suggested the gene as a single copy in A. healyi genome and expressed as a single transcript of approximately 1.0kb. Virulent strains of Acanthamoeba revealed higher level of the AhLBP mRNA expression than soil isolates. Specific binding of the purified recombinant protein to laminin was confirmed by sandwich Western blot. The polypeptide encoded by AhLBP shared substantial identity with the acidic class ribosomal proteins involved in protein synthesis. Therefore, the AhLBP may be multifunctional in A. healyi, acting as a laminin-binding molecule but also playing a role in cell division and growth. AhLBP-EGFP fusion protein expressed in A. healyi was localized mainly at the cell membrane and nucleus and at cytoplasm with lesser degree. N-terminal 64 amino acids were important for the localization at the cell membrane. This is the first description of a cDNA encoding a laminin-binding protein from protozoan parasites.

  12. Subclinical avian influenza A(H5N1) virus infection in human, Vietnam.

    Science.gov (United States)

    Le, Mai Quynh; Horby, Peter; Fox, Annette; Nguyen, Hien Tran; Le Nguyen, Hang Khanh; Hoang, Phuong Mai Vu; Nguyen, Khanh Cong; de Jong, Menno D; Jeeninga, Rienk E; Rogier van Doorn, H; Farrar, Jeremy; Wertheim, Heiman F L

    2013-10-01

    Laboratory-confirmed cases of subclinical infection with avian influenza A(H5N1) virus in humans are rare, and the true number of these cases is unknown. We describe the identification of a laboratory-confirmed subclinical case in a woman during an influenza A(H5N1) contact investigation in northern Vietnam.

  13. Human Infection with Avian Influenza A(H7N9) Virus - China

    Science.gov (United States)

    ... Biorisk reduction Human infection with avian influenza A(H7N9) virus – China Disease outbreak news 18 January 2017 ... laboratory-confirmed human infection with avian influenza A(H7N9) virus and on 12 January 2017, the Health ...

  14. Comparison of the △12 fatty acid desaturase gene between high-oleic and normal-oleic peanut genotypes

    Institute of Scientific and Technical Information of China (English)

    ShanlinYu; Lijuan Pan; Qingli Yang; Ping Min; Zengkai Ren; Hongsheng Zhang

    2008-01-01

    △12fatty acid desaturase gene has been targeted as a logical candidate controlling the high oleate trait in peanut seeds. By RT-PCR method, the full-length cDNAs of △12 fatty acid desaturase gene were isolated from peanut (Arachis hypogaea L.) genotypes with normal and high ratio of oleic to linoleic acid, which were designated AhFAD2B and AhFAD2B', respectively. Sequence alignment of their coding regions revealed that an extra A was inserted at the position +442 bp of AhFAD2B' sequence of high oleic acid genotypes, which resulted in the shift of open reading frame and a truncated protein AhFAD2B', with the loss of one histidine box involved in metal ion complex required for the reduction of oxygen. Analysis of transcript level showed that the expression of △12 fatty acid desaturase gene in high oleic acid genotype was slightly lower than that in normal genotype. The enzyme activity experiment of yeast (Saccharomyces cerevisiae) cell transformed with AhFAD2B or AhFAD2B' proved that only AhFAD2B gene product showed significant A12 fatty acid desaturase activity,but AhFAD2B' gene product did not. These results suggested that the change of AhFAD2B' gene sequence resulted in lower activity or deactivation of △12 fatty acid desaturase in high oleic acid genotype.

  15. Genotoxicity and cytotoxicity of the epoxy resin-based root canal sealer AH plus.

    Science.gov (United States)

    Leyhausen, G; Heil, J; Reifferscheid, G; Waldmann, P; Geurtsen, W

    1999-02-01

    Previous studies with four rapid in vitro and in vivo test systems have shown that the epoxy resin-based root canal sealer AH26 may be genotoxic and cytotoxic (9). The purpose of this study was to determine the cytotoxic and genotoxic effects of the new resinous root canal sealer AH Plus by means of the growth inhibition test with primary human periodontal ligament fibroblasts and permanent 3T3 monolayers, the procaryotic umu test, the eucaryotic DNA synthesis inhibition test, and the in vivo alkaline filter elution test. In addition, Ames tests were performed with extracts from AH Plus. AH Plus caused only slight or no cellular injuries. Furthermore, no genotoxicity and mutagenicity were revealed by AH Plus. These data should be taken into consideration when deciding about a root canal sealer.

  16. Effects of currently used pesticides in the AhR-CALUX assay

    DEFF Research Database (Denmark)

    Long, Manhai; Laier, Peter; Vinggaard, Anne Marie

    2003-01-01

    to be a rapid and sensitive assay for assessing the potency of AhR-activating compounds. We have used the AhR-CALUX assay to investigate the AhR-mediated activity of the persistent organochlorine insecticide dieldrin and twenty-two pesticides currently used in Denmark by employing the rat H4IIE and the human TV......101L hepatoma cell lines. In comparison the results indicated that the rat H4IIE cell line is more sensitive than the human TV101L for detection of TCDD inducing AhR-CALUX activity. The pesticides iprodione, chlorpyrifos and prochloraz showed dose-dependent AhR agonistic effects in both cell lines...... at concentrations above 10, 1 and 1 microM, respectively. However, some pesticides (methiocarb, chlorothalonil, tribenuron-methyl, paclobutrazol and tolchlofos-methyl) elicited differential responses in the two cell lines....

  17. Novel archaeal plasmid pAH1 and its interactions with the lipothrixvirus AFV1

    DEFF Research Database (Denmark)

    Basta, Tamara; Smyth, John; Forterre, Patrick

    2009-01-01

    to establish a system for studying plasmid-virus interactions we characterized the genome of pAH1 which closely resembles those of the Sulfolobus conjugative plasmids pARN3 and pARN4. pAH1 integrates site specifically into, and excises from, the host chromosome indicating a dynamic interaction with the latter....... Although nucleotide sequence comparisons revealed extensive intergenomic exchange during the evolution of archaeal conjugative plasmids, pAH1 was shown to be stably maintained suggesting that the host system is suitable for studying plasmid-virus interactions. AFV1 infection and propagation leads to a loss...... of the circular form of pAH1 and this effect correlates positively with the increase in the intracellular quantity of AFV1 DNA. We infer that the virus inhibits plasmid replication since no pAH1 degradation was observed. This mechanism of archaeal viral inhibition of plasmid propagation is not observed...

  18. Lack of ligand-selective binding of the aryl hydrocarbon receptor to putative DNA binding sites regulating expression of Bax and paraoxonase 1 genes.

    Science.gov (United States)

    DeGroot, Danica E; Hayashi, Ai; Denison, Michael S

    2014-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the biological and toxicological effects of structurally diverse chemicals through its ability to bind specific DNA recognition sites (dioxin responsive elements (DREs)), and activate transcription of adjacent genes. While the DRE has a highly conserved consensus sequence, it has been suggested that the nucleotide specificity of AhR DNA binding may be ligand-dependent. The upstream regulatory regions of the murine Bax and human paraoxonase 1 (PON1) genes reportedly contain unique DRE-like sequences that respond to AhRs activated by some ligands but not others. Given the significant implications of this observation to understanding the diversity in AhR responses and that of other ligand-dependent nuclear receptors, a combination of DNA binding, nuclear translocation and gene expression analysis was used to investigate the molecular mechanisms underlying these ligand-selective responses. Although known AhR agonists stimulated AhR nuclear translocation, DRE binding and gene expression, the ligand-selective DRE-like DNA elements identified in the Bax and PON1 upstream regulatory regions failed to bind ligand-activated AhR or confer AhR-responsiveness upon a reporter gene. These results argue against the reported ligand-selectivity of AhR DNA binding and suggest DNA binding by ligand activated AhR involves DRE-containing DNA.

  19. Forskolin inhibits the Gs-stimulated adenylate cyclase in rat ascites hepatoma AH66F cells.

    Science.gov (United States)

    Miyamoto, K; Sanae, F; Koshiura, R; Matsunaga, T; Hasegawa, T; Takagi, K; Satake, T

    1989-09-01

    Forskolin increased intracellular cyclic AMP and augmented cyclic AMP formation by prostaglandin E1 (PGE1) in normal rat hepatocytes and ascites hepatoma AH66 cells. However, in AH66F cells which were derived from the AH66 cell line, the diterpene only slightly increased the cyclic AMP level, and dose-dependently inhibited the accumulation caused by PGE1. Forskolin dose-dependently activated adenylate cyclase in these membranes, and the magnitude of activation by forskolin was largest in the following order: hepatocytes, AH66 cells, and AH66F cells. This difference may be based on the number of forskolin-binding sites. The binding affinity of forskolin for each cell membrane was similar. The number and affinity of forskolin-binding sites in these cells were not influenced by 5'-guanylylimidodiphosphate [Gpp(NH)p]. In hepatocytes and AH66 cells, forskolin and other adenylate cyclase activators such as PGE1, GTP, Gpp(NH)p, F-, and Mn2+ synergistically increased the enzyme activity. In AH66F cells, the forskolin-stimulated activity was hardly influenced by the GTP analog, and forskolin diminished the activities induced by the GTP analog in a manner similar to that of diterpene alone. Forskolin (10 microM) also significantly inhibited the activities induced by PGE1, GTP, and F-. The effect of forskolin with Mn2+ was additive in AH66F cells. The data suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide-binding protein and the catalytic unit in the membrane of normal hepatocytes and AH66 cells, but it interferes with the coupling in AH66F cells.

  20. Mitochondrial activity and oxidative stress functions are influenced by the activation of AhR-induced CYP1A1 overexpression in cardiomyocytes.

    Science.gov (United States)

    Zhou, Bing; Wang, Xi; Li, Feng; Wang, Yingting; Yang, Lei; Zhen, Xiaolong; Tan, Wuhong

    2017-07-01

    There is an endemic cardiomyopathy currently occurring in China, termed, Keshan disease (KD). The authors previously compared mitochondrial‑associated gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD patients and normal controls, using mitochondria‑focused cDNA microarray technology. The results detected an upregulation of the enzyme‑associated CYP1A1 gene, (ratios ≥2.0). The aryl hydrocarbon receptor (AhR) regulates the expression of numerous cytochrome P450 (CYP) genes including members of the CYP1 family; CYP1A1 and CYP1A2. Several previous studies have suggested roles for the aryl hydrocarbon receptor (AhR) and the genes that it regulates. An example involves cytochrome P4501A1 (CYP1A1), in the pathogenesis of heart failure, cardiac hypertrophy and other cardiomyopathies. Mitochondria comprise ~30% of the intracellular volume in mammalian cardiomyocytes, and subtle alterations in mitochondria can markedly influence cardiomyopathies. The present study investigated alterations in the activity and functions of mitochondria following AhR‑induced overexpression of CYP1A1. AC16 cells were treated with the CYP1A1 inducer 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD), and cytotoxicity was then evaluated in MTT assays. Reverse transcription‑quantitative polymerase chain reactions, western blot analysis and 7‑ethoxyresorufin O‑deacylase assays were performed to analyze the mRNA and protein levels, and the enzymatic activity of CYP1A1. Mitochondrial activity and mass were analyzed using an inverted fluorescence microscope and a fluorescence microplate reader. Reactive oxygen species (ROS) activity was analyzed using flow cytometry. The results of the current study demonstrated that TCDD gradually increased mRNA and protein levels of AhR and CYP1A1, in addition to the enzymatic activity. Mitochondrial activity and the quality of mitochondrial membranes were also significantly attenuated, and mitochondrial ROS

  1. Emergency surveillance for novel influenza A(H7N9) virus in domestic poultry, feral pigeons and other wild birds in Bhutan.

    Science.gov (United States)

    Tenzin, T; Tenzin, S; Tshering, D; Lhamo, K; Rai, P B; Dahal, N; Dukpa, K

    2015-12-01

    Following the March 2013 outbreak of novel avian influenza A(H7N9) virus in humans and the subsequent isolation of the virus from chickens, ducks and pigeons in the People's Republic of China, concerns were raised that the H7N9 virus would spread beyond China through the poultry value chain linking to a number of bordering countries. For this reason, a rapid emergency surveillance exercise took place in Bhutan between May and July 2013 with the objective of determining whether influenza A(H7N9) virus was silently circulating in domestic poultryandwild birds in Bhutan.Atotal of 1716 oropharyngeal,tracheal and cloacal swabs together with faecal droppings were collected from poultry, wild birds and feral pigeons throughout the country; these samples included 150 that had been previously collected for surveillance of influenza A(H5N1) virus. Overall, 733 of the samples were tested. A QIAamp Viral RNA Mini K it was used to extract viral RNA from a mix of oropharyngeal, tracheal and cloacal swabs and faecal droppings. The matrix gene of avian influenza type A virus was detected using a specific real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay, and positive samples were further tested in RT-PCR for simultaneous detection of the H7 and N9 genes. Among the 733 samples tested, 46 (26 prospective, 20 retrospective) were confirmed positive for influenza A, a prevalence of 6.3% (95% CI: 4.6 to 8.3). The influenza A-positive samples were from areas in the south of Bhutan that had experienced previous outbreaks of highly pathogenic influenza A(H5N1). None of the samples tested positive for H7N9 strains, providing evidence that influenza A(H7N9) virus was not present in the sampled population. A risk-based approach for surveillance of influenza A(H7N9) and H5N1 is recommended in Bhutan, based on the epidemiology of the disease in China and other countries in South and Southeast Asia.

  2. Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9)

    NARCIS (Netherlands)

    Chen, Yu; Zhou, Jie; Cheng, Zhongshan; Yang, Shigui; Chu, Hin; Fan, Yanhui; Li, Cun; Wong, Bosco Ho-Yin; Zheng, Shufa; Zhu, Yixin; Yu, Fei; Wang, Yiyin; Liu, Xiaoli; Gao, Hainv; Yu, Liang; Tang, Linglin; Cui, Dawei; Hao, Ke; Bosse, Yohan; Obeidat, Maen; Brandsma, Corry-Anke; Song, You-Qiang; Kai-Wang, Kelvin; Sham, Pak Chung; Yuen, Kwok-Yung; Li, Lanjuan

    2015-01-01

    The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restri

  3. Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9)

    NARCIS (Netherlands)

    Chen, Yu; Zhou, Jie; Cheng, Zhongshan; Yang, Shigui; Chu, Hin; Fan, Yanhui; Li, Cun; Wong, Bosco Ho-Yin; Zheng, Shufa; Zhu, Yixin; Yu, Fei; Wang, Yiyin; Liu, Xiaoli; Gao, Hainv; Yu, Liang; Tang, Linglin; Cui, Dawei; Hao, Ke; Bosse, Yohan; Obeidat, Maen; Brandsma, Corry-Anke; Song, You-Qiang; Kai-Wang, Kelvin; Sham, Pak Chung; Yuen, Kwok-Yung; Li, Lanjuan

    2015-01-01

    The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restri

  4. BALANCED SCORE CARD APPROACH FOR BETTER SHARI’AH CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Sheila Nu Nu Htay

    2013-01-01

    Full Text Available Islamic financial institutions have emerged due to the non-Shari’ah compliant nature of conventional financial from interest, uncertainty, gambling and prohibited activities from the Islamic perspective. In order to achieve the mission of Shari’ah compliance, organizations such as Accounting and Auditing Organization for Islamic Financial Institutions, Islamic Financial Services Board and countries like Malaysia have provided Shari’ah governance guidelines. However, there are some court-cases regarding non-Shari’ah compliant issues and consequently, this has tarnished the reputation of the Islamic financial institutions. There is no guideline on Shari’ah performance measures available to find out to what extent Islamic financial institutions meet its mission. This study tries to fulfill the needs of the industry by providing the balanced score card for Shari’ah governance. This proposed score card is designed based on the concepts of accountability, responsibility, independence and competency of the Shari’ah board members. It suggests measures how any Islamic financial institutions discharge their fiduciary duty towards shareholders, depositors, participants of Islamic industry. The main drive towards Islamic financial institutions is to provide fair and just financial system free insurance, borrowers and society with the expectation of long-term success of the institutions within the Shari’ah framework. The proposed balanced score card is developed based on the opinions of 7 representatives from Islamic banks and 5 representatives from Takaful (Islamic Insurance Operators. It is expected that this score card can be used as a platform for improving the Shari’ah corporate governance of Islamic financial institutions.

  5. Novel influenza A(H1N1) 2009 in vitro reassortant viruses with oseltamivir resistance.

    Science.gov (United States)

    Ottmann, Michèle; Duchamp, Maude Bouscambert; Casalegno, Jean-Sébastien; Frobert, Emilie; Moulès, Vincent; Ferraris, Olivier; Valette, Martine; Escuret, Vanessa; Lina, Bruno

    2010-01-01

    With the recent emergence of the novel A(H1N1) virus in 2009, the efficacy of available drugs, such as neuraminidase (NA) inhibitors, is of great concern for good patient care. Influenza viruses are known to be able to acquire resistance. In 2007, A(H1N1) viruses related to A/Brisbane/59/2007 (H1N1) (A[H1N1] Brisbane-like virus), which are naturally resistant to oseltamivir, emerged. Resistance to oseltamivir can be acquired either by spontaneous mutation in the NA (H275Y in N1), or by reassortment with a mutated NA. It is therefore crucial to determine the risk of pandemic A(H1N1) 2009 virus acquiring resistance against oseltamivir by reassortment. We estimated the capacity of reassortment between the A(H1N1) 2009 virus and an oseltamivir-resistant A(H1N1) Brisbane-like virus by in vitro coinfections of influenza-permissive cells. The screening and the analysis of reassortant viruses was performed by specific reverse transcriptase PCRs and by sequencing. Out of 50 analysed reassortant viruses, two harboured the haemagglutinin (HA) segment from the pandemic A(H1N1) 2009 virus and the mutated NA originated from the A(H1N1) Brisbane-like virus. The replicating capacities of these viruses were measured, showing no difference as compared to the two parental strains, suggesting that acquisition of the mutated NA segment did not impair viral fitness in vitro. Our results suggest that the novel A(H1N1) 2009 virus can acquire by in vitro genetic reassortment the H275Y mutated NA segment conferring resistance to oseltamivir.

  6. Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization

    Energy Technology Data Exchange (ETDEWEB)

    Gualtieri, Maurizio [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Ovrevik, Johan [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Mollerup, Steen [Section for Toxicology, National Institute of Occupational Health, N-0033 Oslo (Norway); Asare, Nana [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Longhin, Eleonora [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Dahlman, Hans-Jorgen [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway); Camatini, Marina [Applied Cell Biology and Particles Effects, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Centre Research POLARIS, Department of Environmental Science, University Milano-Bicocca, Piazza della Scienza 1, 20126 Milano (Italy); Holme, Jorn A., E-mail: jorn.holme@fhi.no [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo (Norway)

    2011-08-01

    Highlights: {yields} PM2.5 induces mitotic arrest in BEAS-2B cells. {yields} PM2.5 induces DNA damage and activates DNA damage response. {yields} AhR regulated genes (Cyp1A1, Cyp1B1 and AhRR) are upregulated after PM exposure. {yields} Mitotic spindle assembly is perturbed in PM exposed cells. - Abstract: Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in 'classical' apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage.

  7. High expression in leaves of the zinc hyperaccumulator Arabidopsis halleri of AhMHX, a homolog of an Arabidopsis thaliana vacuolar metal/proton exchanger.

    Science.gov (United States)

    Elbaz, Benayahu; Shoshani-Knaani, Noa; David-Assael, Ora; Mizrachy-Dagri, Talya; Mizrahi, Keren; Saul, Helen; Brook, Emil; Berezin, Irina; Shaul, Orit

    2006-06-01

    Zn hyperaccumulator plants sequester Zn into their shoot vacuoles. To date, the only transporters implicated in Zn sequestration into the vacuoles of hyperaccumulator plants are cation diffusion facilitators (CDFs). We investigated the expression in Arabidopsis halleri of a homolog of AtMHX, an A. thaliana tonoplast transporter that exchanges protons with Mg, Zn and Fe ions. A. halleri has a single copy of a homologous gene, encoding a protein that shares 98% sequence identity with AtMHX. Western blot analysis with vacuolar-enriched membrane fractions suggests localization of AhMHX in the tonoplast. The levels of MHX proteins are much higher in leaves of A. halleri than in leaves of the non-accumulator plant A. thaliana. At the same time, the levels of MHX transcripts are similar in leaves of the two species. This suggests that the difference in MHX levels is regulated at the post-transcriptional level. In vitro translation studies indicated that the difference between AhMHX and AtMHX expression is not likely to result from the variations in the sequence of their 5' untranslated regions (5'UTRs). The high expression of AhMHX in A. halleri leaves is constitutive and not significantly affected by the metal status of the plants. In both species, MHX transcript levels are higher in leaves than in roots, but the difference is higher in A. halleri. Metal sequestration into root vacuoles was suggested to inhibit hyperaccumulation in the shoot. Our data implicate AhMHX as a candidate gene in metal accumulation or tolerance in A. halleri.

  8. Mouse Oocytes Enable LH-Induced Maturation of the Cumulus-Oocyte Complex via Promoting EGF Receptor-Dependent Signaling

    Science.gov (United States)

    Su, You-Qiang; Sugiura, Koji; Li, Qinglei; Wigglesworth, Karen; Matzuk, Martin M.; Eppig, John J.

    2010-01-01

    LH triggers the maturation of the cumulus-oocyte complex (COC), which is followed by ovulation. These ovarian follicular responses to LH are mediated by epidermal growth factor (EGF)-like growth factors produced by granulosa cells and require the participation of oocyte-derived paracrine factors. However, it is not clear how oocytes coordinate with the EGF receptor (EGFR) signaling to achieve COC maturation. The aim of the present study was to test the hypothesis that oocytes promote the expression of EGFR by cumulus cells, thus enabling them to respond to the LH-induced EGF-like peptides. Egfr mRNA and protein expression were dramatically reduced in cumulus cells of mutant mice deficient in the production of the oocyte-derived paracrine factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). Moreover, microsurgical removal of oocytes from wild-type COCs dramatically reduced expression of Egfr mRNA and protein, and these levels were restored by either coculture with oocytes or treatment with recombinant GDF9 or GDF9 plus recombinant BMP15. Blocking Sma- and Mad-related protein (SMAD)2/3 phosphorylation in vitro inhibited Egfr expression in wild-type COCs and in GDF9-treated wild-type cumulus cells, and conditional deletion of Smad2 and Smad3 genes in granulosa cells in vivo resulted in the reduction of Egfr mRNA in cumulus cells. These results indicate that oocytes promote expression of Egfr in cumulus cells, and a SMAD2/3-dependent pathway is involved in this process. At least two oocyte-derived growth factors, GDF9 and BMP15, are required for EGFR expression by cumulus cells. PMID:20382892

  9. [The formulation of the current management of patients with atypical hyperplasia (AH)].

    Science.gov (United States)

    Gorchev, G; Milkov, V; Popov, I; Rachev, E

    1993-01-01

    The authors study is the receptor status of 16 patients with AH. The amount of ER and PR in patients with AH is compared to the amount of the same receptors in patients with highly differentiated adenocarcinoma. A progestin treatment is proposed for AH together with dynamic evaluation of the amount of ER and PR. In patients ER, PR, even if they have not complete their reproduction, hysterectomy is proposed. The cases ER+, PR+ are actively followed up. Every patients should undergo complex investigation and evaluation in which together with the receptor status extremely important is the routine biopsy.

  10. Kontroversi Produk Bank Sharî‘ah

    Directory of Open Access Journals (Sweden)

    Abdul Rokhim

    2014-01-01

    Full Text Available This paper discusses the views of Muslims on the nature and legitimacy of bank interest as far as Syari’ah law is concerned. Three views are presented here. First is the view of the neo-revivalists who argue that bank interest is legally illegitimate and that it is a form of riba. Second is the view of—among others—Fazlur Rahman who believes that bank interest is not riba. And third is the view that bank interest is in the state of legal doubtfulness (shubhat. We do not support particular view in this paper. But in principle it seems particularly legitimate to argue that Islam is a religion of social wellbeing in which any transaction should be free from such illegitimate practices as riba, gharar (cheating, and financial speculation. However, we also argue that bank interest is too complicated to be equated with riba. There are no accepted standards and qualifications by which the two can be said as the same. To this complex issue we dedicate our paper as a contribution to the issue at hand.

  11. Isolation and expression analysis of glycerol-3-phosphate acyltransferase genes from peanuts (Arachis hypogaea L.

    Directory of Open Access Journals (Sweden)

    Chi, X.

    2015-09-01

    Full Text Available sn-Glycerol-3-phosphate acyltransferase (GPAT catalyzes the committed step in the production of glycerolipids. The functions of GPAT genes have been intensively studied in Arabidopsis, but not in peanuts (Arachis hypogaea L.. In this study, six AhGPAT genes were isolated from peanuts. Quantitative real-time RT-PCR analysis indicated that the AhGPAT9 transcript was more abundant in the stems, flowers, and seeds, whereas the transcript abundances of five other genes were higher in the leaves or flowers than in the other tissues examined. During seed development, the transcript levels of AhGPAT9 gradually increased, whereas the transcript levels of the other five genes decreased. In addition, the levels of AhGPAT2 transcript were distinctly enhanced after exposure to all four kinds of stress treatments except for ABA-treated leaves. The transcripts of AhGPAT1, AhGPAT6, AhGPAT8 and AhATS1 increased substantially in roots exposed to salt, drought, and ABA stress. The expressions of AhGPAT6, AhGPAT8, AhGPAT9 and AhATS1 were slightly higher in leaves under certain stress conditions than under normal conditions. The present study provides significant information for modifying oil deposition and improving the abiotic stress resistance of peanuts through molecular breeding.La aciltransferasa sn-glicerol-3-fosfato (ATGP cataliza el comprometido paso de la producción de glicerolípidos. Las funciones de los genes AhATGP se han estudiado intensivamente en Arabidopsis, pero no en cacahuete (Arachis hypogaea L.. En este estudio, seis genes AhATGP se aislaron a partir de cacahuetes. El análisis a tiempo real RT-PCR cuantitativa indicó que la transcripción AhATGP9 fue más abundante en tallos, flores y semillas, mientras que la abundancia de la transcripción de los otros cinco genes fueron mayores en hojas o flores que en los otros tejidos examinados. Durante el desarrollo de la semilla, los niveles de transcripción de AhATGP9 aumentaron gradualmente

  12. Influenza A Viruses of Swine (IAV-S) in Vietnam from 2010 to 2015: Multiple Introductions of A(H1N1)pdm09 Viruses into the Pig Population and Diversifying Genetic Constellations of Enzootic IAV-S.

    Science.gov (United States)

    Takemae, Nobuhiro; Harada, Michiyo; Nguyen, Phuong Thanh; Nguyen, Tung; Nguyen, Tien Ngoc; To, Thanh Long; Nguyen, Tho Dang; Pham, Vu Phong; Le, Vu Tri; Do, Hoa Thi; Vo, Hung Van; Le, Quang Vinh Tin; Tran, Tan Minh; Nguyen, Thanh Duy; Thai, Phuong Duy; Nguyen, Dang Hoang; Le, Anh Quynh Thi; Nguyen, Diep Thi; Uchida, Yuko; Saito, Takehiko

    2017-01-01

    Active surveillance of influenza A viruses of swine (IAV-S) involving 262 farms and 10 slaughterhouses in seven provinces in northern and southern Vietnam from 2010 to 2015 yielded 388 isolates from 32 farms; these viruses were classified into H1N1, H1N2, and H3N2 subtypes. Whole-genome sequencing followed by phylogenetic analysis revealed that the isolates represented 15 genotypes, according to the genetic constellation of the eight segments. All of the H1N1 viruses were entirely A(H1N1)pdm09 viruses, whereas all of the H1N2 and H3N2 viruses were reassortants among 5 distinct ancestral viruses: H1 and H3 triple-reassortant (TR) IAV-S that originated from North American pre-2009 human seasonal H1, human seasonal H3N2, and A(H1N1)pdm09 viruses. Notably, 93% of the reassortant IAV-S retained M genes that were derived from A(H1N1)pdm09, suggesting some advantage in terms of their host adaptation. Bayesian Markov chain Monte Carlo analysis revealed that multiple introductions of A(H1N1)pdm09 and TR IAV-S into the Vietnamese pig population have driven the genetic diversity of currently circulating Vietnamese IAV-S. In addition, our results indicate that a reassortant IAV-S with human-like H3 and N2 genes and an A(H1N1)pdm09 origin M gene likely caused a human case in Ho Chi Minh City in 2010. Our current findings indicate that human-to-pig transmission as well as cocirculation of different IAV-S have contributed to diversifying the gene constellations of IAV-S in Vietnam.

  13. Cloning and Characterization of AhFT in Peanut (Arachis hypogaea)%花生 AhFT 基因的克隆与序列分析

    Institute of Scientific and Technical Information of China (English)

    葛姗姗; 唐桂英; 陈霞霞; 付旭; 柳展基; 毕玉平

    2014-01-01

    FT (Flowering Locus T ) encoding florigens plays important roles in the control of the transi-tion between vegetative and reproductive growth and promoting flowering.In this study, a cDNA encoding the FT homologue was isolated from peanut (Arachis hypogaea ) by RT-PCR and named as AhFT . Sequence analysis indicated that the cDNA of AhFT was 893 bp long and contained a single open reading frame with 534 bp in length.The predicted AhFT protein has 177 amino acids with an estimated molecular mass of 19.95 kD and an isoelectric point of 6.9.Phylogenetic analysis showed AhFT belonged to the FT-like subfamily.These results indicate AhFT may play important roles in flowering.%FT (Flowering Locus T )作为“成花素”在成花转变及促进开花上起重要作用。本研究利用分子克隆和 RT-PCR 方法,从花生中克隆了一个与 FT 同源的 cDNA 序列,命名为 AhFT,该序列长度为893 bp,开放阅读框长度为534 bp,推测编码蛋白含有177个氨基酸,分子量为19.95 kD,等电点为6.9。通过与其他植物 PEBP 蛋白序列的比对,发现花生 FT 基因属于 FT-Like 家族,可能在控制植物开花中起重要作用。

  14. Community-acquired pneumonia due to pandemic A(H1N12009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection.

    Directory of Open Access Journals (Sweden)

    Ronan J Murray

    Full Text Available BACKGROUND: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N12009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. METHODOLOGY/PRINCIPAL FINDINGS: Patients with community-acquired pneumonia (CAP caused by co-infection with pandemic A(H1N12009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N12009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N12009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N12009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL. CONCLUSIONS/SIGNIFICANCE: Clinicians managing patients with pandemic A(H1N12009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic

  15. 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.

    Science.gov (United States)

    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

  16. AHS and CASI Processing for the REFLEX Remote Sensing Campaign: Methods and Results

    Directory of Open Access Journals (Sweden)

    Miguel Eduardo de

    2015-12-01

    Full Text Available The airborne spectroradiometers AHS and CASI were used as a source of hyperspectral and thermal remote sensing data during the REFLEX campaign. Data geolocation and a first simple atmospheric correction was performed by INTA in near-real time with a specific on-site setup and distributed to all campaign participants. In this paper we present briefly the AHS and CASI REFLEX flight campaign followed by a detailed description of the methodology used for image processing and finally the results obtained in terms of image quality. As a conclusion, near-real time processing for AHS and CASI level 1 geolocated products was successful as most of CASI level 2 results but further work is needed for achieving accurate AHS level 2 products.

  17. Comparative Resistance of AH26 and a New Sealer Prototype to a Bacterial Challenge

    Directory of Open Access Journals (Sweden)

    Derek Duggan

    2012-01-01

    Full Text Available Objective. This study compared the leakage resistance of a New Sealer Prototype (NSP with a traditional sealer (AH 26 in Resilon-filled roots subjected to a bacterial challenge. Study Design. 41 roots were instrumented to ISO size 50 apically. Group 1 (=20 contained Resilon and AH 26 sealer and roots in group 2 (=21 contained Resilon and NSP. Roots were embedded in a dual-chamber model with the upper chamber containing Streptococcus mutans inoculum. Evidence of bacterial penetration was observed for 1 month. Fisher's Test was used to analyze the data. Results. 8 of 20 roots (40% in the AH 26 group demonstrated leakage whereas 3 of 21 roots (14% in the NSP group leaked. The difference in leakage rates was not statistically significant (=0.053. Conclusion. The traditional sealer (AH 26 demonstrated increased leakage rates compared to the New Sealer Prototype (NSP, but the difference did not reach statistical significance in this study.

  18. Comparison of Portfolio Selection and Performance: Shari’ah-Compliant and Socially Responsible Investment Portfolios

    Directory of Open Access Journals (Sweden)

    Mehmet Asutay

    2015-04-01

    Full Text Available This study examines the effect of Islamic screening criteria on Shari’ah-compliant portfolio selection and performance compared to Socially Responsible Investment (SRI portfolio. Each portfolio constructed from 15 stocks based on FTSE 100 using data from year 1997. Mean-variance portfolio optimization is employed with some financial ratios added as constraints for the Shari’ah portfolio. Annual expected return of each portfolio from 2008 to 2013 is used to calculate Sharpe’s ratio, Treynor ratio and Jensen’s alpha as the performance measurement tools. Macroeconomic variables are assessed using ordinary least square to examine whether they influence the portfolios’ expected returns or not. The result finds that Shari’ah portfolio has a better performance than SRI from year 2008 to 2010 shown by higher value of the measurement tools. However, from 2011 to 2013, SRI portfolio has better performance than Shari’ah portfolio. 

  19. Intense Seasonal A/H1N1 Influenza in Mexico, Winter 2013–2014

    Science.gov (United States)

    Dávila-Torres, Javier; Chowell, Gerardo; Borja-Aburto, Víctor H.; Viboud, Cécile; Grajalez-Muñiz, Concepción; Miller, Mark. A.

    2014-01-01

    Background and Aims A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013–2014 following a mild 2012–2013 A/H3N2 influenza season. Methods We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013–2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system. Results A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October 1, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30–59 years and lower among younger age groups for the 2013–2014 A/H1N1 season compared to the previous A/H1N1 season in 2011–2012 (χ2 test, p <0.001). The reproduction number for the winter 2013–2014 influenza season in central Mexico was estimated at 1.3–1.4, in line with that reported for the 2011–2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009. Conclusions We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013–March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011–2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics. PMID:25446616

  20. A novel computational approach for the prediction of networked transcription factors of aryl hydrocarbon-receptor-regulated genes.

    Science.gov (United States)

    Kel, Alexander; Reymann, Susanne; Matys, Volker; Nettesheim, Paul; Wingender, Edgar; Borlak, Jürgen

    2004-12-01

    A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of coexpressed genes. Our method enabled an identification of combinations of multiple transcription factor binding sites regulating the concerted expression of genes. In this article, we study genes whose expression is regulated by a ligand-activated transcription factor, aryl hydrocarbon receptor (AhR), that mediates responses to a variety of toxins. AhR-mediated change in expression of AhR target genes was measured by oligonucleotide microarrays and by reverse transcription-polymerase chain reaction in human and rat hepatocytes. Promoters and long-distance regulatory regions (>10 kb) of AhR-responsive genes were analyzed by the genetic algorithm and a variety of other computational methods. Rules were established on the local oligonucleotide context in the flanks of the AhR binding sites, on the occurrence of clusters of AhR recognition elements, and on the presence in the promoters of specific combinations of multiple binding sites for the transcription factors cooperating in the AhR regulatory network. Our rules were applied to search for yet unknown Ah-receptor target genes. Experimental evidence is presented to demonstrate high fidelity of this novel in silico approach.

  1. Influenza A(H3N2) Outbreak at Transit Center at Manas, Kyrgyzstan, 2014

    Science.gov (United States)

    2015-01-01

    Article 3. DATES COVERED (From – To) December 2013-February 2014 4. TITLE AND SUBTITLE Influenza A(H3N2) Outbreak at Transit Center at Manas...support in response to a moderate outbreak of influenza at the Transit Center at Manas (Kyrgyzstan). A total of 215 individuals presented with... influenza -like illness symptoms from 3 December 2013 through 28 February 2014. There were 85 specimens positive for influenza (18 influenza A(H1N1

  2. Children hospitalized with influenza pneumonia AH1N1/2009 pandemic in the INSN

    OpenAIRE

    Miranda-Choque, Edwin; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Infectólogo.; Ramírez, Carlos; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Infectólogo.; Candela-Herrera, Jorge; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Díaz, Javier; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Fernández, Ana; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Kolevic, Lenka; Servicio de Infectología, Instituto Nacional de Salud del Niño. Lima, Perú. Médico Pediatra.; Segura, Eddy R.; Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia. Lima, Perú. Escuela de Medicina, Univesidad Peruana de Ciencias Aplicadas. Lima, Perú. Médico Epidemiólogo Clínico.; Farfán-Ramos, Sonia; Hospital de Emergencias Pediátricas. Lima, Perú. Enfermera, especialista en Enfermería Pediátrica, Magister en Salud Pública y Comunitaria, Magister en Administración de Salud.

    2014-01-01

    ObjectiveTo determine the clinical and demographic characteristics of pneumonia with influenza virus AH1N1/2009 pandemic at the National Institute of Child. Methods. Retrospective case series in children hospitalized for influenza pneumonia pandemic AH1N1/2009 in a pediatric hospital. Reviewed the medical records between the months of June to September 2009. All cases had virological confirmation, we describe the clinical characteristics and conditions of severity. Results. A total of 74 ...

  3. Altered adrenergic response and specificity of the receptors in rat ascites hepatoma AH130.

    Science.gov (United States)

    Sanae, F; Miyamoto, K; Koshiura, R

    1989-11-15

    Adenylate cyclase activation through adrenergic receptors in rat ascites hepatoma (AH) 130 cells in response to adrenergic drugs was studied, and receptor binding and displacement were compared with those of normal rat hepatocytes. Epinephrine (Epi) and norepinephrine (NE) activated AH130 adenylate cyclase about half as much as isoproterenol (IPN) but equaled IPN after treatment with the alpha-antagonist phentolamine or islet-activating protein (IAP). The three catecholamines in hepatocytes were similar regardless of phentolamine or IAP. These catecholamines activated adenylate cyclase in order of IPN greater than NE greater than Epi in AH130 cells but IPN greater than Epi greater than NE in hepatocytes. We then used the alpha 1-selective ligand [3H]prazosin, the alpha 2-selective ligand [3H]clonidine, and the beta-ligand [125I]iodocyanopindolol [( 125I]ICYP), and found that AH130 cells had few prazosin-binding sites, about eight times as many clonidine-binding sites with high affinity, and many more ICYP-binding sites than in hepatocytes. The dissociation constant (Ki) of the beta 1-selective drug metoprolol by Hofstee plots for AH130 cells was lower than that for hepatocytes. The inhibition of specific ICYP binding by the beta 2-selective agonist salbutamol for AH130 cells gave only one Ki value which was much higher than both high and low Ki values of the drug for hepatocytes. These findings indicate that the alpha- and beta-adrenergic receptors in hepatocytes are predominantly alpha 1-type and beta 2-type, but that those in AH130 cells are predominantly alpha 2-type and beta 1-type, and the low adrenergic response of AH130 cells is due to the dominant appearance of alpha 2-adrenergic receptors, linked with the inhibitory guanine-nucleotide binding regulatory protein, instead of alpha 1-adrenergic receptors, and beta 1-adrenergic receptors with low affinity for the hormone.

  4. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated to hereditary neuropathy with liability to pressure palsies (HNPP) and revealed after influenza AH1N1 vaccination.

    Science.gov (United States)

    Remiche, Gauthier; Abramowicz, Marc; Mavroudakis, Nicolas

    2013-12-01

    Neurological complications of AH1N1 vaccination such as Guillain-Barré syndrome were described in the previous years. Several reports suggest that hereditary neuropathies may be a predisposing factor for immune-mediated neuropathies. We report the case of a 54-year-old female who developed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 5 weeks after AH1N1 vaccination. She had no previous neurological history, but neurophysiological features led us to suspect an underlying hereditary neuropathy. PMP22 gene analysis showed a typical deletion, confirming the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). We observed a significant clinical and neurophysiological improvement of the neuropathy after intravenous immunoglobulin treatment. This is, to our knowledge, the first reported case of CIDP potentially triggered by AH1N1 vaccination. This and previous observations suggest that genetic-determined neuropathies could predispose to the occurrence of immune-mediated neuropathies. One must recall the possibility of a superimposed hereditary neuropathy like HNPP in patients with a clinical presentation of CIDP, especially when positive family history or unexpected neurophysiological features are present.

  5. Generation of (F+2)_AH Centres in Sodium Ion Doped KCl:CO^{2-3}

    Science.gov (United States)

    Diaf, M.; Chihi, I.; Hamaïdia, A.; Akrmi, El.

    1996-01-01

    We demonstrate that (F+2)AH centres of KCl may be obtained from crystals doped with K{2}CO{3} and NaCl, grown by the Czochralski method in open atmosphere. The optical properties of (F+2)AH centres thus produced are exactly the same as those of (F+2)AH centres prepared by the usual technique, which involves superoxide doping and a controlled atmosphere. Nous montrons que les centres (F+2)AH de KCl peuvent être obtenus à partir de cristaux dopés par K{2}CO{3} et NaCl, fabriqués par la méthode de Czochralski à l'air libre. Les propriétés optiques des centres (F+2)AH ainsi produits sont exactement les mêmes que celles des centres (F+2)AH préparés par la technique habituelle, qui comporte le dopage par un superoxyde et l'emploi d'une atmosphère contrôlée.

  6. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  7. Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

    Science.gov (United States)

    Gachara, George; Symekher, Samuel; Otieno, Michael; Magana, Japheth; Opot, Benjamin; Bulimo, Wallace

    2016-06-01

    An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability.

  8. [Antigenic anachronism of influenza viruses A(H2N2) in Leningrad in 1980. II. The laboratory characteristics of influenza A/Leningrad/80 viruses].

    Science.gov (United States)

    Golubev, D B; Galitarov, S S; Poliakov, Iu M; Litvinova, O M; Bannikov, A I

    1984-11-01

    As indicated by the results of the hemagglutination inhibition (HAI) test, influenza viruses A/Leningrad/80 contain hemagglutinin (HA), similar to that of virus A/Singapore/1/57 (H2N2). Neuraminidase contained in viruses A/Leningrad/80 belongs to serological subtype N2 and is similar to that of virus A/Singapore/1/57 (H2N2). No differences in the polypeptide composition of the virus-induced proteins of viruses A/Leningrad/527/80, A/Leningrad/549/80, A/Leningrad/553/80 and virus A/Singapore/1/57 used as reference have been detected in the study of their electrophoretic mobility in polyacrylamide gel, as well as the mobility of duplexes obtained by the hybridization of the virion and complement RNA of viruses A/Leningrad/553/80 and A/Singapore/1/57. The results of the HAI test with antisera to purified HA indicate that virus A/Leningrad/549/80 contains HA similar to that of viruses A(H2N2) isolated in 1957, but not in 1964. The HAI test with the sera of polecats having the infection permits the differentiation of viruses A/Leningrad/80 from epidemic viruses A(H2N2) isolated in 1957-1965, including reference virus A/Singapore/1/57. In relation to the latter, the isolates of 1980 are older antigenic mutants. The isolates of 1980 are distinguished from virus A(H2N2), isolated in 1975 from the system of persisting influenza infection in a tissue culture, by mutation in NS-gene and the properties of RNA-polymerase. The authenticity of the isolation of viruses A(H2N2) in Leningrad in 1980 has been proved.

  9. Ah Q Zheng Zhuan's Retranslation Viewed From the Translator'Skopos%Ah Q Zheng Zhuan's Retranslation Viewed From the Translator' Skopos

    Institute of Scientific and Technical Information of China (English)

    滕丽梅

    2016-01-01

    This paper attempts to do researches into retranslation of literary works from the perspective of Skopos theory, taking three English versions of Ah Q Zheng Zhuan as research objects. Studying retranslation of literary works from the perspective of Skopos theory is persuasive and can help to recognize the phenomenon of literary retranslation comprehensively and deeply to some extent.

  10. Hook-up of GluA2, GRIP and liprin-α for cholinergic muscarinic receptor-dependent LTD in the hippocampus

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2009-06-01

    Full Text Available Abstract The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP, and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-α. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR, a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.

  11. EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    2014-01-01

    Full Text Available Our previous studies showed that urinary Tamm–Horsfall glycoprotein (THP potently enhanced polymorphonuclear neutrophil (PMN phagocytosis. However, the domain structure(s, signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS, THP, or human recombinant epidermal growth factor (EGF was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase.

  12. Endothelin-1 induces proliferation of human lung fibroblasts and IL-11 secretion through an ET(A) receptor-dependent activation of MAP kinases.

    Science.gov (United States)

    Gallelli, Luca; Pelaia, Girolamo; D'Agostino, Bruno; Cuda, Giovanni; Vatrella, Alessandro; Fratto, Donatella; Gioffrè, Vincenza; Galderisi, Umberto; De Nardo, Marilisa; Mastruzzo, Claudio; Salinaro, Elisa Trovato; Maniscalco, Mauro; Sofia, Matteo; Crimi, Nunzio; Rossi, Francesco; Caputi, Mario; Costanzo, Francesco S; Maselli, Rosario; Marsico, Serafino A; Vancheri, Carlo

    2005-11-01

    Endothelin-1 (ET-1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET-1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET-1 in the presence or absence of an overnight pre-treatment with either ET(A) or ET(B) selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen-activated protein kinases (MAPK). ET-1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL-6/IL-11 release into cell culture supernatants. All these effects were inhibited by the selective ET(A) antagonist BQ-123, but not by the specific ET(B) antagonist BQ-788. The stimulatory influence of ET-1 on IL-11, but not on IL-6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET-1 exerts a profibrogenic action via an ET(A) receptor-dependent, MAPK-mediated induction of IL-11 release and cell proliferation.

  13. AhR- and ER-mediated activities in human blood samples collected from PCB-contaminated and background region in Slovakia

    Energy Technology Data Exchange (ETDEWEB)

    Pliskova, M. [Veterinary Researcch Institute, Brno (Czech Republic); Canton, R.F.; Duursen, M.B.M. van [Utrecht Univ. (NL). Institute for Risk Assessment Sciences (IRAS)] (and others)

    2004-09-15

    Endocrine disruption mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) by polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs) has been studied extensively both in vivo and in vitro. Non-ortho- and mono-ortho-substituted polychlorinated biphenyls (PCBs) are potent AhR agonists therefore, increased dioxin-like activity of complex blood samples might reflect an increased exposure to PCBs. The induction of expression of CYP1A1 and CYP1B1 in different tissues, including lymphocytes, also depends on activation of AhR and it could be useful as a potential biomarker of exposure to dioxin-like compounds. Using various in vivo and in vitro models, the exposure to PCBs or hydroxy-PCBs has been reported to lead to either induction of ER-mediated activity or to an antiestrogenic effect associated with a suppression of estradiol-induced ER-dependent gene expression. Nevertheless, relative (anti)estrogenic potencies of a large set of prevalent environmental PCBs have not been yet compared in a single bioassay. A cross-talk between AhR and ER has been suggested to lead to a suppression of ER-mediated gene expression. Therefore, presence of dioxin-like compounds in blood could potentially suppress the ER-mediated activity. Additionally, AhR-dependent induction of CYP1A1 and especially CYP1B1, two enzymes involved in oxidative metabolism of estradiol and other estrogens, might enhance the metabolism of estradiol and it has been suggested to cause a potential depression of estrogen levels in the body. The aim of the present study was to determine dioxin-like, estrogenic and antiestrogenic activities in human blood samples collected in two Eastern Slovakia regions differently polluted with PCBs using established in vitro bioassays. We also studied mRNA expression of CYP1A1 and 1B1 in lymphocytes and the genotypes of CYP1B1 as possible biomarkers of exposure for PCBs and related compounds. The biological data obtained

  14. Aryl Hydrocarbon Receptor (AhR Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2014-01-01

    Full Text Available Background. Aryl hydrocarbon receptor (AhR, a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic diseases. We sought to investigate whether AhR plays a role in mediating cockroach allergen-induced allergic immune responses. Methods. AhR expression in human lung fibroblasts from asthmatic and healthy individuals and in cockroach extract (CRE treated human lung fibroblasts (WI-38 was examined. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. The role of latent TGFβ1 binding protein-1 (LTBP1 in mediating TCDD induced active TGFβ1 release was also examined. Results. AhR expression was higher in airway fibroblasts from asthmatic subjects as compared to healthy controls. AhR in fibroblasts was activated by TCDD with an increased expression of cyp1a1 and cyp1b1. Increased AhR expression was observed in CRE-treated fibroblasts. Importantly, CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. Reduced TGFβ1 production was further confirmed in fibroblasts with AhR knockdown. Moreover, AhR knockdown inhibited CRE induced fibroblast differentiation. Furthermore, TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. Conclusion. These results provide evidence for the role of AhR in modulating cockroach allergen-induced immune responses through controlling the active TGFβ1 release, suggesting a possible synergistic effect between exposure to allergens and environmental chemicals on the development of allergic diseases.

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

    Science.gov (United States)

    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.

  16. Emergence in China of human disease due to avian influenza A(H10N8)--cause for concern?

    Science.gov (United States)

    To, Kelvin K W; Tsang, Alan K L; Chan, Jasper F W; Cheng, Vincent C C; Chen, Honglin; Yuen, Kwok-Yung

    2014-03-01

    In December 2013, China reported the first human case of avian influenza A(H10N8). A 73-year-old female with chronic diseases who had visited a live poultry market succumbed with community-acquired pneumonia. While human infections with avian influenza viruses are usually associated with subtypes prevalent in poultries, A(H10N8) isolates were mostly found in migratory birds and only recently in poultries. Although not possible to predict whether this single intrusion by A(H10N8) is an accident or the start of another epidemic like the preceding A(H7N9) and A(H5N1), several features suggest that A(H10N8) is a potential threat to humans. Recombinant H10 could attach to human respiratory epithelium, and A(H10N4) virus could cause severe infections in minks and chickens. A(H10N8) viruses contain genetic markers for mammalian adaptation and virulence in the haemagglutinin (A135T, S138A[H3 numbering]), M1(N30D, T215A), NS1(P42S) and PB2(E627K) protein. Studies on this human A(H10N8) isolate will reveal its adaptability to humans. Clinicians should alert the laboratory to test for A(H5,6,7,9,10) viruses in patients with epidemiological exposure in endemic geographical areas especially when human influenza A(H1,3) and B are negative. Vigilant virological and serological surveillance for A(H10N8) in human, poultry and wild bird is important for following the trajectory of this emerging influenza virus.

  17. The five AhMTP1 zinc transporters undergo different evolutionary fates towards adaptive evolution to zinc tolerance in Arabidopsis halleri.

    Science.gov (United States)

    Shahzad, Zaigham; Gosti, Françoise; Frérot, Hélène; Lacombe, Eric; Roosens, Nancy; Saumitou-Laprade, Pierre; Berthomieu, Pierre

    2010-04-15

    Gene duplication is a major mechanism facilitating adaptation to changing environments. From recent genomic analyses, the acquisition of zinc hypertolerance and hyperaccumulation characters discriminating Arabidopsis halleri from its zinc sensitive/non-accumulator closest relatives Arabidopsis lyrata and Arabidopsis thaliana was proposed to rely on duplication of genes controlling zinc transport or zinc tolerance. Metal Tolerance Protein 1 (MTP1) is one of these genes. It encodes a Zn(2+)/H(+) antiporter involved in cytoplasmic zinc detoxification and thus in zinc tolerance. MTP1 was proposed to be triplicated in A. halleri, while it is present in single copy in A. thaliana and A. lyrata. Two of the three AhMTP1 paralogues were shown to co-segregate with zinc tolerance in a BC1 progeny from a cross between A. halleri and A. lyrata. In this work, the MTP1 family was characterized at both the genomic and functional levels in A. halleri. Five MTP1 paralogues were found to be present in A. halleri, AhMTP1-A1, -A2, -B, -C, and -D. Interestingly, one of the two newly identified AhMTP1 paralogues was not fixed at least in one A. halleri population. All MTP1s were expressed, but transcript accumulation of the paralogues co-segregating with zinc tolerance in the A. halleri X A. lyrata BC1 progeny was markedly higher than that of the other paralogues. All MTP1s displayed the ability to functionally complement a Saccharomyces cerevisiae zinc hypersensitive mutant. However, the paralogue showing the least complementation of the yeast mutant phenotype was one of the paralogues co-segregating with zinc tolerance. From our results, the hypothesis that pentaplication of MTP1 could be a major basis of the zinc tolerance character in A. halleri is strongly counter-balanced by the fact that members of the MTP1 family are likely to experience different evolutionary fates, some of which not concurring to increase zinc tolerance.

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

    Science.gov (United States)

    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.

  19. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.

    Science.gov (United States)

    Belanov, Sergei S; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E

    2015-11-27

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.

  20. Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry, Vietnam, 2009–2011

    OpenAIRE

    Nguyen, Ha T.; Nguyen, Tung; Mishin, Vasiliy P.; Sleeman, Katrina; Balish, Amanda; Jones, Joyce; Creanga, Adrian; Marjuki, Henju; Timothy M Uyeki; Nguyen, Dang H.; Nguyen, Diep T.; Do, Hoa T.; Klimov, Alexander I.; Davis, Charles T.; Gubareva, Larisa V.

    2013-01-01

    We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009–2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation ...

  1. Persistent detection of avian influenza A/H7N9 virus among poultry in Huzhou City, China, in the summer of 2013

    Directory of Open Access Journals (Sweden)

    Jiankang Han

    2014-09-01

    Full Text Available In eastern China, live poultry markets were successively re-opened in the summer of 2013 following their closure in April 2013. We detected influenza A/H7N9 RNA with positive rates from 4% to 22.2% among poultry samples in targeted markets in Huzhou City, China, from August 6 to September 24, 2013. Phylogenetic analyses of hemagglutinin and neuraminidase genes confirmed that the strain prevalent among poultry in Huzhou City in the summer of 2013 belonged to the same genotype as those capable of infecting humans. These results raise concern for a further outbreak of H7N9 in the cooler season.

  2. Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands

    Directory of Open Access Journals (Sweden)

    Vezina Chad M

    2010-10-01

    Full Text Available Abstract Background Two year cancer bioassays conducted by the National Toxicology Program have shown chronic exposure to dioxin-like compounds (DLCs to lead to the development of both neoplastic and non-neoplastic lesions in the hepatic tissue of female Sprague Dawley rats. Most, if not all, of the hepatotoxic effects induced by DLC's are believed to involve the binding and activation of the transcription factor, the aryl hydrocarbon receptor (AhR. Toxicogenomics was implemented to identify genomic responses that may be contributing to the development of hepatotoxicity in rats. Results Through comparative analysis of time-course microarray data, unique hepatic gene expression signatures were identified for the DLCs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD (100 ng/kg/day and 3,3',4,4',5-pentachlorobiphenyl (PCB126 (1000 ng/kg/day and the non-DLC 2,2',4,4',5,5',-hexachlorobiphenyl (PCB153 (1000 μg/kg/day. A common time independent signature of 41 AhR genomic biomarkers was identified which exhibited at least a 2-fold change in expression following subchronic (13-wk and chronic (52-wk p.o. exposure to TCDD and PCB126, but not the non DLC, PCB153. Real time qPCR analysis validated that 30 of these genes also exhibited at least a 2-fold change in hepatic expression at 24 hr following a single exposure to TCDD (5 μg/kg, po. Phenotypic anchoring was conducted which identified forty-six genes that were differently expressed both following chronic p.o. exposure to DLCs and in previously reported studies of cholangiocarcinoma or hepatocellular adenoma. Conclusions Together these analyses provide a comprehensive description of the genomic responses which occur in rat hepatic tissue with exposure to AhR ligands and will help to isolate those genomic responses which are contributing to the hepatotoxicity observed with exposure to DLCs. In addition, the time independent gene expression signature of the AhR ligands may assist in identifying other agents

  3. The Volatility of Indonesia Shari’ah Capital Market Stock Price Toward Macro Economics Variable

    Directory of Open Access Journals (Sweden)

    Helma Malini

    2014-08-01

    Full Text Available Shari’ah stock market is also affected by many highly interrelated economic, social, political andother factor, same as the conventional stock market, the interaction between macroeconomic variablesand Shari’ah stock market creating volatility in the stock price as a response towards severalshocks. The sensitivity of Shari’ah stock market towards shocks happened related with the futureexpectation of micro and macro factor in one country which can be predict or unpredictable.There are six macroeconomic variables that used in this research; inflation, exchange rate, interestrate, dow jones index, crude oil palm price, and FED rate. Using vector error correction model(VECM, the result shows that domestic macroeconomic variables that significantly affect IndonesiaShari’ah compliance for long term, while for international macroeconomic variables the selectedvariable such as FED rate and Dow Jones Index are not significantly affected Indonesia Shari’ahcompliance both in short term and long term. Keywords: Indonesia Shari’ah compliance, Macro Economic Indicators, Impulse Response Function,Stock Price Volatility

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

    Science.gov (United States)

    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

  5. Ethanol withdrawal is required to produce persisting N-methyl-D-aspartate receptor-dependent hippocampal cytotoxicity during chronic intermittent ethanol exposure

    Science.gov (United States)

    Reynolds, Anna R.; Berry, B. Jennifer N.; Sharrett-Field, Lynda; Prendergast, Mark A.

    2015-01-01

    Chronic intermittent ethanol consumption is associated with neurodegeneration and cognitive deficits in preclinical laboratory animals and in the clinical population. While previous work suggests a role for neuroadaptations in the N-methyl-D-aspartate (NMDA) receptor in the development of ethanol dependence and manifestation of withdrawal, the relative roles of ethanol exposure and ethanol withdrawal in producing these effects have not been fully characterized. To examine underlying cytotoxic mechanisms associated with CIE exposure, organotypic hippocampal slices were exposed to 1–3 cycles of ethanol (50 mM) in cell culture medium for 5 days, followed by 24-hours of ethanol withdrawal in which a portion of slices were exposed to competitive NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 40 µM). Cytotoxicity was assessed using immunohistochemical labeling of neuron specific nuclear protein (NeuN; Fox-3), a marker of mature neurons, and thionine (2%) staining of Nissl bodies. Multiple cycles of CIE produced neurotoxicity, as reflected in persisting losses of neuron NeuN immunoreactivity and thionine staining in each of the primary cell layers of the hippocampal formation. Hippocampi aged in vitro were significantly more sensitive to the toxic effects of multiple CIEs than were non-aged hippocampi. This effect was not demonstrated in slices exposed to continuous ethanol, in the absence of withdrawal, or to a single exposure/withdrawal regimen. Exposure to APV significantly attenuated the cytotoxicity observed in the primary cell layers of the hippocampus. The present findings suggest that ethanol withdrawal is required to produce NMDA receptor-dependent hippocampal cytotoxicity, particularly in the aging hippocampus in vitro. PMID:25746220

  6. Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    Science.gov (United States)

    Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T

    2016-02-01

    Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory.

  7. Control of βAR- and N-methyl-D-aspartate (NMDA Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    Directory of Open Access Journals (Sweden)

    Andrew Chay

    2016-02-01

    Full Text Available Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs, facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs. To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA, and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory.

  8. Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus.

    Science.gov (United States)

    Mango, D; Braksator, E; Battaglia, G; Marcelli, S; Mercuri, N B; Feligioni, M; Nicoletti, F; Bashir, Z I; Nisticò, R

    2017-01-27

    Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na(+) channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca(2+) and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

  9. Latent inhibition of cued fear conditioning: an NMDA receptor-dependent process that can be established in the presence of anisomycin.

    Science.gov (United States)

    Lewis, Michael C; Gould, Thomas J

    2004-08-01

    Much of the research examining the biological basis for long-term memories has focused on mechanisms that support the formation of conditioned associations. Less information is available on biological mechanisms which underlie processes that modify the strength of conditioned associations. Latent inhibition is a phenomenon by which pre-exposure to a to-be-conditioned stimulus (CS) weakens subsequent conditioning of that CS to an unconditioned stimulus (US). Here we report that latent inhibition of cued fear conditioning is dependent on NMDA receptor activation. MK-801 (1 mg/kg), an NMDA receptor antagonist, abolished latent inhibition of cued fear conditioning. This dose of MK-801 administered before training did not disrupt cued fear conditioning. Conversely, anisomycin (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of cued fear conditioning when administered 20 min before, immediately after, or 2, 4, 6, or 8 h after CS pre-exposure. Furthermore, continuous anisomycin administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to pre-exposure) did not disrupt latent inhibition of cued fear conditioning. In addition, anisomycin had no effect on a long-lasting version of latent inhibition of cued fear conditioning that was maintained over a 7-day interval. Anisomycin administered before training, however, disrupted learning of the CS-US association. These findings suggest that latent inhibition of cued fear conditioning is a long-lasting NMDA receptor-dependent process that can develop during the inhibition of protein synthesis.

  10. Apolipoprotein E competitively inhibits receptor-dependent low density lipoprotein uptake by the liver but has no effect on cholesterol absorption or synthesis in the mouse.

    Science.gov (United States)

    Woollett, L A; Osono, Y; Herz, J; Dietschy, J M

    1995-01-01

    This study examines the question of whether apolipoprotein E (apoE) alters steady-state concentrations of plasma cholesterol carried in low density lipoproteins (LDL-C) by acting as a competitive inhibitor of hepatic LDL uptake or by altering the rate of net cholesterol delivery from the intestinal lumen to the liver. To differentiate between these two possibilities, rates of cholesterol absorption and synthesis and the kinetics of hepatic LDL-C transport were measured in vivo in mice with either normal (apoE+/+) or zero (apoE-/-) levels of circulating apoE. Rates of cholesterol absorption were essentially identical in both genotypes and equaled approximately 44% of the daily dietary load of cholesterol. This finding was consistent with the further observation that the rates of cholesterol synthesis in the liver (approximately 2,000 nmol/h) and extrahepatic tissues (approximately 3,000 nmol/h) were also essentially identical in the two groups of mice. However, the apparent Michaelis constant for receptor-dependent hepatic LDL-C uptake was markedly lower in the apoE-/- mice (44 +/- 4 mg/dl) than in the apoE+/+ animals (329 +/- 77 mg/dl) even though the maximal transport velocity for this uptake process was essentially the same (approximately 400 micrograms/h per g) in the two groups of mice. These studies, therefore, demonstrate that apoE-containing lipoproteins can act as potent competitive inhibitors of hepatic LDL-C transport and so can significantly increase steady-state plasma LDL-C levels. This apolipoprotein plays no role, however, in the regulation of cholesterol absorption, sterol biosynthesis, or hepatic LDL receptor number, at least in the mouse. PMID:8618929

  11. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  12. ISOLATION AND PURIFICATION OF A KRINGLE 5 FROM HUMAN PLASMINOGEN USING AH-SEPHAROSE

    Directory of Open Access Journals (Sweden)

    Kapustianenko L. G.

    2014-08-01

    Full Text Available Our aim was to develop a method for isolation of human plasminogen kringle 5 possessing functional activity. The proposed method includes the following steps: hydrolysis of plasminogen with elastase, separation of mini-plasminogen from kringle fragments 1–3 and 4 on Lys-Sepharose, mini-plasminogen hydrolysis with pepsin, affinity chromatography on AH-Sepharose and polyacrilamide gel electrophoresis. We obtained the electrophoretically pure fragment of human plasminogen kringle 5 showing functional activity towards the ligands with high and low molecular mass. Weight yield was 3.8% that corresponds to 25.3% of the theoretically possible. It was established that affinity chromatography on AH-Sepharose was the sufficient step to isolate kringle 5 from mini-plasminogen hydrolysate with pepsin. This approach does not require additional purification steps while the ability of kringle 5 to bind specifically to AH-Sepharose demonstrates the functional activity of the kringle.

  13. AH-MAC: Adaptive Hierarchical MAC Protocol for Low-Rate Wireless Sensor Network Applications

    Directory of Open Access Journals (Sweden)

    Adnan Ismail Al-Sulaifanie

    2017-01-01

    Full Text Available This paper proposes an adaptive hierarchical MAC protocol (AH-MAC with cross-layer optimization for low-rate and large-scale wireless sensor networks. The main goal of the proposed protocol is to combine the strengths of LEACH and IEEE 802.15.4 while offsetting their weaknesses. The predetermined cluster heads are supported with an energy harvesting circuit, while the normal nodes are battery-operated. To prolong the network’s operational lifetime, the proposed protocol transfers most of the network’s activities to the cluster heads while minimizing the node’s activity. Some of the main features of this protocol include energy efficiency, self-configurability, scalability, and self-healing. The simulation results showed great improvement of the AH-MAC over LEACH protocol in terms of energy consumption and throughput. AH-MAC consumes eight times less energy while improving throughput via acknowledgment support.

  14. AhR transcription serum activity of Inuit´s across Greenlandic districts

    DEFF Research Database (Denmark)

    Long, Manhai; Deutch, Bente; Bonefeld-Jørgensen, Eva Cecilie

    2007-01-01

    Background: Human exposure to lipophilic persistent organic pollutants (POPs) including Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous...... food. Conclusions: i) We observed that the proportion of dioxin like (DL) compounds in the POP i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL......-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain....

  15. SOC Estimation of LiFePO4 Battery based on Improved Ah Integral Method

    Directory of Open Access Journals (Sweden)

    Zheng ZHU

    2013-07-01

    Full Text Available State of charge (SOC is the most important status parameters of energy storage system, which is able to predict the available mileage of electric vehicle. In fact, the accuracy of SOC estimation plays a vital role in the usability and security of the battery. To fully consider the practical demands, a novel method to predict SOC of LiFePO4 battery is presented in this paper, which defines the correct coefficient separately under two working conditions of charging and discharging. Based on effective factors such as coulombic efficiency, charge and discharge current, and temperature, an Ah integral SOC estimation method with two kinds of efficiency correct coefficients is established by performing massive experimental study. Experiments prove that the estimated error of SOC is less than 5%. Compared with the original Ah method, the improved Ah method is more advantageous in the accuracy and reliability.

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

    Directory of Open Access Journals (Sweden)

    Catherine M. Rondelli

    2016-01-01

    Full Text Available 7,12-Dimethylbenz(aanthracene (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.

  17. An Exploratory Study of the Rhetoric in CSR Reports: A Comparison of Shari’ah Compliant Company and Non –Shari’ah Compliant Company in Malaysia

    Directory of Open Access Journals (Sweden)

    Abdul Razak Rafizan

    2017-01-01

    Full Text Available This paper advances previous research in corporate social reporting (CSR by using a taxonomy of five distinct rhetorical strategies to examine any differences in term of type of ethical categories and to identify moral attitudes towards different societal activities between Shari’ah compliant company Bank Islam Malaysia Berhad (BIMB and Non-Shari’ah compliant company Malayan Banking Berhad (Maybank. The data is analyzed using content analysis. The findings revealed that there are different rhetoric applied in both types of companies such as Agency (profit, Benefit (collective welfare, Compliance (law and contracts, Duty and Ethos (virtue. In term of moral attitudes, both types of companies disclosed relatively similar behaviour and commitment towards CSR. This research is the first of its kind to be conducted in Malaysia by using this new approach and will contribute new insights to existing CSR literatures in Malaysia.

  18. Benarkah Kita Murji’ah? Catatan atas Artikel Prof. Dr. Fauzan Saleh

    Directory of Open Access Journals (Sweden)

    Amal Fathullah Zarkasyi

    2014-11-01

    Full Text Available This is a special note on the article written by Fauzan Saleh entitled Kita Masih Murji’ah: Mencari Akar Teologi Pemahaman Umat Islam Indonesia published in Tsaqafah Volume 7, No. 2, October 2009. The author notes that the article could plunge Muslims to the wrong conception. Fauzan begins his article on Caliph Uthman’s nepotism when designating Amr bin Ash as governor of Egypt, Mua’wiyah as governor of Sham and Sa’ad bin Abi Waqas as governor of Iraq and Persia. Further this article notes concerning the definition of Ahl al- Sunnah wa al-Jama’ah. In addition, the author sees Fauzan does not fully understand this concept. Thus, because he classified both Maturidist and Asy’arist only into this group, without explaining their true set of belief. Actually the truth about Ahl al-Sunnah wa al-Jama’ah is the groups who have unanimity in beliefs, traditions and the status of Prophet Muhammad (Peace be upon him and the the very righteous people among Muslims in Islam. They are the prophet’s companions and Tabi’in (followers, and the schoolars who followed their guidance, and their way in terms of faith, words, and deeds until the Day of Judgment. From this point of view, the criticism persists about the actors a great sin whereby this article parsed differences between Ahlusunah and Murji’ah. According to the author, Fauzan has been on failure when he drew a hasty conclusion at the similarity belief of Murji’ah and Ahlusunah, whereas Ahlusunah’s creed is just a continuation of Murji’ah’s. As clearly written in Fauzan’s conclusions of the article, despite Murji’ah creed is no longer known at this time, but this concept still remains sustainable in Islamic theology.

  19. Epidemiology of human influenza A(H7N9) infection in Hong Kong.

    Science.gov (United States)

    Leung, Yiu-Hong; To, May-Kei; Lam, Tsz-Sum; Yau, Shui-Wah; Leung, Oi-Shan; Chuang, Shuk-Kwan

    2017-04-01

    We conducted a case series study to review the epidemiology of human influenza A(H7N9) infection reported in Hong Kong. We reviewed case records of confirmed human cases of influenza A(H7N9) infection reported in Hong Kong in the 2013-2014 winter season. We compared the median viral shedding duration and interval from illness onset to initiation of oseltamivir treatment between severe and mild cases. We estimated the incubation period of influenza A(H7N9) virus from cases with a single known date of poultry exposure. A total of 10 cases were reported and all were imported infection from Mainland China. Four patients died and the cause of death was related to influenza A(H7N9) infection in two patients. The median interval from illness onset to initiation of oseltamivir treatment for the severe cases (4.5 days) was significantly longer than the mild cases (2 days; p = 0.025). Severe cases had a significantly longer viral shedding duration than mild cases (p = 0.028). The median incubation period for cases with a single known exposure date was 4 days. Nasopharyngeal aspirate taken from the 88 close contacts of the 10 patients all tested negative for influenza A virus using reverse transcription polymerase chain reaction. Delayed administration of antiviral treatment may be associated with a more severe illness for influenza A(H7N9) infection. Despite our aggressive contact tracing policy with laboratory testing of all close contacts, no secondary case was identified which implied that the potential of human-to-human transmission of the circulating influenza A(H7N9) virus remains low. Copyright © 2015. Published by Elsevier B.V.

  20. Month of the Year and Pre- Holiday Effects In Indonesia and Malaysia Shari’ah Compliance

    Directory of Open Access Journals (Sweden)

    Helma Malini

    2014-01-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} This paper investigates the existence of two anomalies in Indonesia and Malaysia Shari’ah compliance; the month of the year and pre-holiday effect, and their implication for stock market efficiency. Investing in Shari’ah compliant is different from investing in conventional stock. Conventional stock market followed the capital market set of rules and law, while Shari’ah follows not only followed the capital market set of laws but also the Islamic principles. Most of the previous studies investigated issues related to the conventional stock market, this study take one step further by investigating issue related to Shari’ah compliant instrument and make comparison between both Shari’ah compliance stock market in Indonesia and Malaysia. We document high and significant returns in month and pre-holiday in Indonesia and Malaysia stock market that represent by the Shari’ah compliance. Our result indicate that the month of the year effect is prevalent in Indonesia and Malaysia Shari’ah compliance.   Keywords: Calendar effects, Indonesia and Malaysia Shari’ah compliance, Month of the year and pre-holiday effects

  1. Influenza A(H10N7) Virus in Dead Harbor Seals, Denmark

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Hansen, Mette Sif; Holm, Elisabeth

    2015-01-01

    Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined.......Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined....

  2. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Paola Faverio

    2014-01-01

    Full Text Available We present the results of bronchoalveolar lavage (BAL performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS. Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

  3. Experimental Evidence for Hydrogen Tunneling when the Isotopic Arrhenius Prefactor (AH/AD) is Unity

    Science.gov (United States)

    Sharma, Sudhir C.; Klinman, Judith P.

    2009-01-01

    The temperature dependence of the kinetic isotope effect (KIE) is one of the major tools used for the investigation of hydrogen tunneling in condensed phase. Hydrogen transfer reactions displaying isotopic Arrhenius prefactor ratios (AH/AD) of unity are generally ascribed to a semi-classical mechanism. Here, we have identified a double mutant of soybean lipoxygenase (SLO-1, an enzyme previously shown to follow quantum mechanical hydrogen tunneling), that displays an AH/AD of unity and highly elevated (non-classical) KIEs. This observation highlights the shortcoming of assigning a hydrogen transfer reaction to a semi-classical model based solely on an Arrhenius prefactor ratio. PMID:19061319

  4. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    Science.gov (United States)

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  5. Penyelesaian Sengketa antara Bank Sharî‘ah dengan Nasabah Bermasalah melalui Badan Arbitrase Sharî‘ah Nasional (BASYARNAS menurut UU No. 30 tahun 1999

    Directory of Open Access Journals (Sweden)

    Sulistyowati Sulistyowati

    2015-09-01

    Full Text Available This study deals with dispute settlement between Bank Syari’ah and its customers through the National Shari’ah Arbitration Board (BASYARNAS. It focuses to elaborate the procedures of dispute settlement between Bank Syari’ah and its customers of financing from the perspective of Islamic law according to Bill No. 30/1999 above law No. 30 year 1999. Based on procedures as mentioned in the bill with regard to arbitration and alternative dispute resolution, Basyarnas, in proofing and resolving cases, has fulfilled the procedures and satisfied the conflicting parties with justice, so there is no need to appeal and reconsideration. This means that Basyarnas has conducted dispute resolution according to the existing procedures. The dispute settlement has also been in accordance with the Qur’ân and other Islamic legal rules which consist of the principles of power and mandate applied by the arbitrator in deciding and resolving the dispute. The board—as an independent institution—has setttled the disputes on the basis of justice for all parties, rejected the act of bribery since the cost is measurable. In addition, Basyarnas also gives strong emphasis on the principle of equality, friendship, consistence and response-bility in resolving disputes.

  6. A/H6N1亚型禽流感病毒致病性评估及与2009A/H1N1亚型流感病毒在哺乳动物体内的遗传兼容性%Evaluation of the pathogenicity of A/H6N1 avian influenza virus and its genetic compatibility with 2009 A/H1N1 pandemic influenza virus in mammalian models

    Institute of Scientific and Technical Information of China (English)

    程凯慧; 王铁成; 杨松涛; 黄耕; 赵永坤; 高玉伟; 华育平; 夏咸柱; 于志君; 忻悦; 张坤; 丁洁; 黄靖; 岳秀芳; 杨霞; 乔军

    2013-01-01

    Objective A/H6N1 avian influenza virus has become an epidemic virus in poultry in China, posing a significant threat to public health. In order to evaluate the capacity of pathogenesis and reassortment of H6N1 virus in mammalians, we first evaluated the pathogenicity of H6N1 virus to mice, and then evaluated the compatibility between H6N1 virus and 2009 A/H1N1 pandemic viruse. Methods For the mouse infection experiment, the mice were inoculated intrana-sally with l01 EID50 - 106EID50 A/H6N1 AIV (A/Mallard/SanJiang/275/2007 , which was isolated from wild ducks) , and virological and histological data were collected by clinical sign observation, virus titration, and histopathology with HE staining. For the reassorment experiment in guinea pigs, the animals were inoculated with mixed A/H6N1 and A/H1N1 influenza viruses ( A/Changchun/01/2009 ) . The nasal washes of guinea pigs were collected every day, and reassortment viruses were obtained by plaque purification and identified by sequence analysis. Results In the mouse infection experiment, the mice were directly infected with H6N1 AIV virus, but were not lethal. The group of mice inoculated with 10 EID50 showed body weight loss, decreased activity, dorsal hair disordered, and tachypnea at day 15 after infection (DPI15). However, the clinical symptoms disappeared at DPI10. The virus titration results showed that the A/H6N1 virus mainly replicated in the lung, trachea and turbinate of mice, and the virus titers were up to 10 4,5/mL. Using HE staining, the pathological examination found that the lungs of the 10 EID50 group showed pathological changes, including alveolar wall thickening, infiltration of inflammatory cells, fibrin exudation and slight bleeding. In the reassorment experiment of guinea pigs, six reassortant virus strains were recovered with different gene segments derived from H6N1 and H1N1 viruses after three-time plaque purification. The results indicated that A/H6N1 and A/H1N1 influenza virus have high

  7. Molecular findings from influenza A(H1N1pdm09 detected in patients from a Brazilian equatorial region during the pandemic period

    Directory of Open Access Journals (Sweden)

    Maria José Couto Oliveira

    2014-11-01

    Full Text Available After the World Health Organization officially declared the end of the first pandemic of the XXI century in August 2010, the influenza A(H1N1pdm09 virus has been disseminated in the human population. In spite of its sustained circulation, very little on phylogenetic data or oseltamivir (OST resistance is available for the virus in equatorial regions of South America. In order to shed more light on this topic, we analysed the haemagglutinin (HA and neuraminidase (NA genes of influenza A(H1N1pdm09 positive samples collected during the pandemic period in the Pernambuco (PE, a northeastern Brazilian state. Complete HA sequences were compared and amino acid changes were related to clinical outcome. In addition, the H275Y substitution in NA, associated with OST resistance, was investigated by pyrosequencing. Samples from PE were grouped in phylogenetic clades 6 and 7, being clustered together with sequences from South and Southeast Brazil. The D222N/G HA gene mutation, associated with severity, was found in one deceased patient that was pregnant. Additionally, the HA mutation K308E, which appeared in Brazil in 2010 and was only detected worldwide the following year, was identified in samples from hospitalised cases. The resistance marker H275Y was not identified in samples tested. However, broader studies are needed to establish the real frequency of resistance in this Brazilian region.

  8. Permissive changes in the neuraminidase play a dominant role in improving the viral fitness of oseltamivir-resistant seasonal influenza A(H1N1) strains.

    Science.gov (United States)

    Abed, Yacine; Pizzorno, Andrés; Bouhy, Xavier; Boivin, Guy

    2015-02-01

    Permissive neuraminidase (NA) substitutions such as R222Q, V234M and D344N have facilitated the emergence and worldwide spread of oseltamivir-resistant influenza A/Brisbane/59/2007 (H1N1)-H275Y viruses. However, the potential contribution of genetic changes in other viral segments on viral fitness remains poorly investigated. A series of recombinant A(H1N1)pdm09 and A/WSN/33 7:1 reassortants containing the wild-type (WT) A/Brisbane/59/2007 NA gene or its single (H275Y) and double (H275Y/Q222R, H275Y/M234V and H275Y/N344D) variants were generated and their replicative properties were assessed in vitro. The Q222R reversion substitution significantly reduced viral titers when evaluated in both A(H1N1)pdm09 and A/WSN/33 backgrounds. The permissive role of the R222Q was further confirmed using A/WSN/33 7:1 reassortants containing the NA gene of the oseltamivir-susceptible or oseltamivir-resistant influenza A/Mississippi/03/2001 strains. Therefore, NA permissive substitutions play a dominant role for improving viral replication of oseltamivir-resistant A (H1N1)-H275Y viruses in vitro.

  9. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

    Directory of Open Access Journals (Sweden)

    Akahoshi Eiichi

    2009-06-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR. This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR. Methods N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA. Results Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE, though AHRE-III was not identical to XRE, the conventional AhR-binding motif. Conclusion Our results suggest TCDD directly regulate the dopamine system by TH gene

  10. Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination

    NARCIS (Netherlands)

    Gefenaite, Giedre; Tacken, Margot; Bos, Jens; Stirbu-Wagner, Irina; Korevaar, Joke C.; Stolk, Ronald P.; Wolters, Bert; Bijl, Marc; Postma, Maarten J.; Wilschut, Jan; Nichol, Kristin L.; Hak, Eelko

    2013-01-01

    INTRODUCTION: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. METHODS: VE against influenza and/or pneumonia was ass

  11. Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination.

    NARCIS (Netherlands)

    Gefenaite, G.; Tacken, M.; Bos, J.; Stirbu-Wagner, I.; Korevaar, J.C.; Stolk, R.P.; Wolters, B.; Bijl, M.; Postma, M.J.; Wilschut, J.; Nichol, K.L.; Hak, E.

    2013-01-01

    Introduction: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. Methods: VE against influenza and/or pneumonia was ass

  12. Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination.

    NARCIS (Netherlands)

    Gefenaite, G.; Tacken, M.; Bos, J.; Stirbu-Wagner, I.; Korevaar, J.C.; Stolk, R.P.; Wolters, B.; Bijl, M.; Postma, M.J.; Wilschut, J.; Nichol, K.L.; Hak, E.

    2013-01-01

    Introduction: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. Methods: VE against influenza and/or pneumonia was

  13. Third Wave of Influenza A(H7N9) Virus from Poultry, Guangdong Province, China, 2014–2015

    Science.gov (United States)

    Xie, Shumin; Jia, Weixin; Lin, Yicun; Xing, Kaixiang; Ren, Xingxing; Qi, Wenbao

    2015-01-01

    Fourteen influenza A(H7N9) viruses were isolated from poultry or the environment in live poultry markets in Guangdong Province, China during 2014−2015. Phylogenetic analysis showed that all viruses were descended from viruses of the second wave of influenza A(H7N9) virus infections during 2013. These viruses can be divided into 2 branches. PMID:26291620

  14. Third Wave of Influenza A(H7N9) Virus from Poultry, Guangdong Province, China, 2014-2015.

    Science.gov (United States)

    Xie, Shumin; Jia, Weixin; Lin, Yicun; Xing, Kaixiang; Ren, Xingxing; Qi, Wenbao; Liao, Ming

    2015-09-01

    Fourteen influenza A(H7N9) viruses were isolated from poultry or the environment in live poultry markets in Guangdong Province, China during 2014-2015. Phylogenetic analysis showed that all viruses were descended from viruses of the second wave of influenza A(H7N9) virus infections during 2013. These viruses can be divided into 2 branches.

  15. High rate of A(H1N1pdm09 infections among rural Thai villagers, 2009-2010.

    Directory of Open Access Journals (Sweden)

    Benjawan Khuntirat

    Full Text Available Pandemic influenza A(H1N1pdm09 emerged in Thailand in 2009. A prospective longitudinal adult cohort and household transmission study of influenza-like illness (ILI was ongoing in rural Thailand at the time of emergence. Symptomatic and subclinical A(H1N1pdm09 infection rates in the cohort and among household members were evaluated.A cohort of 800 Thai adults underwent active community-based surveillance for ILI from 2008-2010. Acute respiratory samples from ILI episodes were tested for A(H1N1pdm09 by qRT-PCR; acute and 60-day convalescent blood samples were tested by A(H1N1pdm09 hemagglutination inhibition assay (HI. Enrollment, 12-month and 24-month follow-up blood samples were tested for A(H1N1pdm09 seroconversion by HI. Household members of influenza A-infected cohort subjects with ILI were enrolled in household transmission investigations in which day 0 and 60 blood samples and acute respiratory samples were tested by either qRT-PCR or HI for A(H1N1pdm09. Seroconversion between annual blood samples without A(H1N1pdm09-positive ILI was considered as subclinical infection.The 2-yr cumulative incidence of A(H1N1pdm09 infection in the cohort in 2009/2010 was 10.8% (84/781 with an annual incidence of 1.2% in 2009 and 9.7% in 2010; 83.3% of infections were subclinical (50% in 2009 and 85.9% in 2010. The 2-yr cumulative incidence was lowest (5% in adults born ≤ 1957. The A(H1N1pdm09 secondary attack rate among household contacts was 47.2% (17/36; 47.1% of these infections were subclinical. The highest A(H1N1pdm09 secondary attack rate among household contacts (70.6%, 12/17 occurred among children born between 1990 and 2003.Subclinical A(H1N1pdm09 infections in Thai adults occurred frequently and accounted for a greater proportion of all A(H1N1pdm09 infections than previously estimated. The role of subclinical infections in A(H1N1pdm09 transmission has important implications in formulating strategies to predict and prevent the spread of A(H1N1pdm

  16. Possible pandemic threat from new reassortment of influenza A(H7N9) virus in China.

    Science.gov (United States)

    Meng, Z; Han, R; Hu, Y; Yuan, Z; Jiang, S; Zhang, X; Xu, J

    2014-02-13

    Avian influenza A(H7N9) virus re-emerged in China in December 2013, after a decrease in the number of new cases during the preceding six months. Reassortment between influenza A(H7N9) and local H9N2 strains has spread from China's south-east coast to other regions. Three new reassortments of A(H7N9) virus were identified by phylogenetic analysis: between A(H7N9) and Zhejiang-derived strains, Guangdong/Hong Kong-derived strains or Hunan-derived A(H9N2) strains. Our findings suggest there is a possible risk that a pandemic could develop.

  17. IEEE 802.11ah: A Technology to Face the IoT Challenge

    Directory of Open Access Journals (Sweden)

    Victor Baños-Gonzalez

    2016-11-01

    Full Text Available Since the conception of the Internet of things (IoT, a large number of promising applications and technologies have been developed, which will change different aspects in our daily life. This paper explores the key characteristics of the forthcoming IEEE 802.11ah specification. This future IEEE 802.11 standard aims to amend the IEEE 802.11 legacy specification to support IoT requirements. We present a thorough evaluation of the foregoing amendment in comparison to the most notable IEEE 802.11 standards. In addition, we expose the capabilities of future IEEE 802.11ah in supporting different IoT applications. Also, we provide a brief overview of the technology contenders that are competing to cover the IoT communications framework. Numerical results are presented showing how the future IEEE 802.11ah specification offers the features required by IoT communications, thus putting forward IEEE 802.11ah as a technology to cater the needs of the Internet of Things paradigm.

  18. Inhibition of Vibrio anguillarum by Pseudomonas fluorescens AH2, a possible probiotic treatment of fish

    DEFF Research Database (Denmark)

    Gram, Lone; Melchiorsen, Jette; Spanggaard, Bettina

    1999-01-01

    To study the possible use of probiotics in fish farming, we evaluated the in vitro and in vivo antagonism of antibacterial strain Pseudomonas fluorescens strain AH2 against the fish- pathogenic bacterium Vibrio anguillarum. As iron is important in virulence and bacterial interactions, the effect....... fluorescens AH2 inhibited the growth of V. anguillarum during coculture, independently of the iron concentration, when the initial count of the antagonist was 100 to 1,000 times greater that of the fish pathogen. These in vitro results were successfully repeated in vivo. A probiotic effect in vivo was tested...... by exposing rainbow trout (Oncorynchus mykiss Walbaum) to P. fluorescens AH2 at a density of 10(5) CFU/ml for 5 days before a challenge with V. anguillarum at 10(4) to 10(5) CFU/ml for 1 h. Some fish were also exposed to P. fluorescens AH2 at 10(7) CFU/ml during the 1-h infection. The combined probiotic...

  19. Job Performance Tests for U/AH-1 Helicopter Mechanics. Volume 1: Hands- On Performance Test

    Science.gov (United States)

    1991-11-01

    Hands-on performance tests and job knowledge tests were developed for MOS 6114 (U/AH-1 helicopter mechanic) as part of the Marine Corps Job ... Performance Measurement Project. The purpose of this information memorandum is to disseminate these performance measures to Marine Corps personnel managers

  20. Influenza A(H1N1pdm09-associated pneumonia deaths in Thailand.

    Directory of Open Access Journals (Sweden)

    Charatdao Bunthi

    Full Text Available BACKGROUND: The first human infections with influenza A(H1N1pdm09 virus were confirmed in April 2009. We describe the clinical and epidemiological characteristics of influenza A(H1N1pdm09-associated pneumonia deaths in Thailand from May 2009-January 2010. METHODS: We identified influenza A(H1N1pdm09-associated pneumonia deaths from a national influenza surveillance system and performed detailed reviews of a subset. RESULTS: Of 198 deaths reported, 49% were male and the median age was 37 years; 146 (73% were 20-60 years. Among 90 deaths with records available for review, 46% had no identified risk factors for severe influenza. Eighty-eight patients (98% received antiviral treatment, but only 16 (18% initiated therapy within 48 hours of symptom onset. CONCLUSIONS: Most influenza A(H1N1pdm09 pneumonia fatalities in Thailand occurred in adults aged 20-60 years. Nearly half lacked high-risk conditions. Antiviral treatment recommendations may be especially important early in a pandemic before vaccine is available. Treatment should be considered as soon as influenza is suspected.

  1. Architectuur als beschavingsideaal: Het bezield modernisme van A.H. Wegerif

    NARCIS (Netherlands)

    Thomas, H.

    2014-01-01

    Architecture as civilizing ideal - The inspired modernism of A.H. Wegerif Ahazuerus Hendrikus (Henk) Wegerif was born in Apeldoorn on 13th of April 1888, the son of Gerrit Wegerif and Elsje Breman. Both his father and grandfather were building contractors, as was his paternal uncle, Chris Wegerif.

  2. HOW SHOULD SHARI’AH PRINCIPLES BE APPLIED IN MODERN COMPANY?

    Directory of Open Access Journals (Sweden)

    Burhanuddin Susamto

    2012-06-01

    Full Text Available The purpose of this study is to show why the modern business institution (company should be Islamized, and to suggest ways in which shari’ah principles can be applied in the company. To achieve this purpose, we should understand how company be islamized in comprehensive and integrated  manner through the Islamic law perspective, with the contemporary issues like underlying contract of company,  legal entity, and the concept of liability. The resolution of these issues is important to assert that shari’ah principles could be applied in the modern company by integrating approach. An integrating approach in the treating of these issues has, however, been lacking, nor has it been subjected to a thorough legal analysis through the principles of Islamic business law.   Tujuan dari pembahasan ini adalah untuk menunjukkan bahwa institusi bisnis modern (perusahaan harus diislamisasi, dan member masukan cara-cara bagimana prinsip- prinsip shari’ah dapat ditetapkan dalam perusahaan. Untuk mencapai tujuan ini, kita perlu memahami bagaimana perusahaan diislamisasi secara menyeluruh dan terintegrasi melalui perspektif hukum Islam terhadap persoalan kontemporer, seperti landasan kontrak perusahaan, badan hukum, dan konsep liabilitas. Solusi dari persoalan ini sangat penting untuk   menegaskan bahwa prinsip-prinsip shari’ah dapat ditetapkan pada perusahaan modern melalui pendekatan integrasi. Bagaimanapun, pendekatan integrasi dalam menyikapi persoalan ini jarang dilakukan, disamping tidak menjadi tema analisis melalui prinsip-prinsip hukum bisnis Islami.

  3. Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients

    NARCIS (Netherlands)

    Friesema, Ingrid H. M.; Meijer, Adam; van Gageldonk-Lafeber, Arianne B.; van der Lubben, Mariken; van Beek, Janko; Donker, Ge A.; Prins, Jan M.; de Jong, Menno D.; Boskamp, Simone; Isken, Leslie D.; Koopmans, Marion P. G.; van der Sande, Marianne A. B.

    2012-01-01

    The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory-confirmed Dutch cases were examined. An episode lasted a median of 7 5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. S

  4. Human influenza A(H7N9) virus infection associated with poultry farm, Northeastern China.

    Science.gov (United States)

    Fan, Ming; Huang, Biao; Wang, Ao; Deng, Liquan; Wu, Donglin; Lu, Xinrong; Zhao, Qinglong; Xu, Shuang; Havers, Fiona; Wang, Yanhui; Wu, Jing; Yin, Yuan; Sun, Bingxin; Yao, Jianyi; Xiang, Nijuan

    2014-11-01

    We report on a case of human infection with influenza A(H7N9) virus in Jilin Province in northeastern China. This case was associated with a poultry farm rather than a live bird market, which may point to a new focus for public health surveillance and interventions in this evolving outbreak.

  5. Inhibition of Vibrio anguillarum by Pseudomonas fluorescens AH2, a possible probiotic treatment of fish

    DEFF Research Database (Denmark)

    Gram, Lone; Melchiorsen, Jette; Spanggaard, Bettina;

    1999-01-01

    To study the possible use of probiotics in fish farming, we evaluated the in vitro and in vivo antagonism of antibacterial strain Pseudomonas fluorescens strain AH2 against the fish- pathogenic bacterium Vibrio anguillarum. As iron is important in virulence and bacterial interactions, the effect....... fluorescens AH2 inhibited the growth of V. anguillarum during coculture, independently of the iron concentration, when the initial count of the antagonist was 100 to 1,000 times greater that of the fish pathogen. These in vitro results were successfully repeated in vivo. A probiotic effect in vivo was tested...... by exposing rainbow trout (Oncorynchus mykiss Walbaum) to P. fluorescens AH2 at a density of 10(5) CFU/ml for 5 days before a challenge with V. anguillarum at 10(4) to 10(5) CFU/ml for 1 h. Some fish were also exposed to P. fluorescens AH2 at 10(7) CFU/ml during the 1-h infection. The combined probiotic...

  6. Development, documentation and correlation of a NASTRAN vibration model of the AH-1G helicopter airframe

    Science.gov (United States)

    Cronkhite, J. D.

    1976-01-01

    NASTRAN was evaluated for vibration analysis of the helicopter airframe. The first effort involved development of a NASTRAN model of the AH-1G helicopter airframe and comprehensive documentation of the model. The next effort was to assess the validity of the NASTRAN model by comparisons with static and vibration tests.

  7. Activation of the Ah receptor by extracts of dietary herbal supplements, vegetables, and fruits

    NARCIS (Netherlands)

    Jeuken, A.; Keser, B.J.G.; Khan, E.; Brouwer, A.; Koeman, J.H.; Denison, M.S.

    2003-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by a structurally diverse range of synthetic and natural chemicals, and it mediates the toxic and biological effects of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

  8. Architectuur als beschavingsideaal: Het bezield modernisme van A.H. Wegerif

    NARCIS (Netherlands)

    Thomas, H.

    2014-01-01

    Architecture as civilizing ideal - The inspired modernism of A.H. Wegerif Ahazuerus Hendrikus (Henk) Wegerif was born in Apeldoorn on 13th of April 1888, the son of Gerrit Wegerif and Elsje Breman. Both his father and grandfather were building contractors, as was his paternal uncle, Chris Wegerif.

  9. Syari’ah, Fiqih dan Sebuah Perspektif tentang Tarjîh

    Directory of Open Access Journals (Sweden)

    Miftahul Huda

    2014-01-01

    Full Text Available This paper takes into account the very fact that Syari’ah has been a subject of controversy over centuries. Its interpretation in the form of fiqh (Islamic jurisprudence is a strong indication that Syari’ah is not immune from personal subjectivication. Fiqh is quite personal whereby a jurist would read the message of Syari’ah and attempt to give his personal and subjective interpretation of it. Nonetheless, the paper is also of the argument that this controversy is in itself a source of the dynamics of Syari’ah. It is due to this controversy–otherwise known as the legal dispute- that fiqh is capable of being developed over times. Some substances of fiqh are responses to the opposing views on some issues. Not less important than this is to delve into the factors that triggered such controversy and dispute. The paper speaks of three factors, namely the nature of subject-matter, the way the jurists interpret it, and the social circumstances that surround the jurists and help shape their way of thinking. The first is epistemological, the second methodological, whereas the third to sociological. The three factors are inter-related and form as it were the comprehensive legal products which the Muslims currently inherited. The Tarjih in the meantime, is a form of a legal product, which serves both as a social and intellectual modality for the Muslims in their daily lives.

  10. Data of evolutionary structure change: 1A2AH-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1A2AH-2NOTA 1A2A 2NOT H A NLLQFNKMIKEETG-KNAIPFYAFYGCYCGGGGNGKPKD...278 2NOT A 2.2960000038146973 tion> -0.0820000022649765 -0.5170000195503235 ...>-0.38600000739097595 0.8169999718666077 0.45399999618530273 0.3540000021457672 ...2NOT A 2NOTA

  11. A Challenge for Social Studies Educators: Teaching about Islam, "Jihad," and "Shari'ah" Law

    Science.gov (United States)

    Moore, James R.

    2012-01-01

    In this article, the author investigates the controversial curricular and instructional aspects of teaching about Islam in social studies courses. Specifically, the author discusses pedagogically sound approaches to teaching about "jihad" and "Shari'ah" law, two of the most important and controversial concepts in Islam that often generate intense…

  12. The Influenza A(H1N1)v Pandemic: An Exploratory System Dynamics Approach

    NARCIS (Netherlands)

    Pruyt, E.; Hamarat, C.

    2010-01-01

    This paper presents a small exploratory System Dynamics model related to the dynamics of the 2009 flu pandemic, also known as the Mexican flu, swine flu, or A(H1N1)v. The model was developed in May 2009 in order to quickly foster understanding about the possible dynamics of this new flu variant and

  13. AH-DB: collecting protein structure pairs before and after binding.

    Science.gov (United States)

    Chang, Darby Tien-Hao; Yao, Tsung-Ju; Fan, Chen-Yu; Chiang, Chih-Yun; Bai, Yi-Han

    2012-01-01

    This work presents the Apo-Holo DataBase (AH-DB, http://ahdb.ee.ncku.edu.tw/ and http://ahdb.csbb.ntu.edu.tw/), which provides corresponding pairs of protein structures before and after binding. Conformational transitions are commonly observed in various protein interactions that are involved in important biological functions. For example, copper-zinc superoxide dismutase (SOD1), which destroys free superoxide radicals in the body, undergoes a large conformational transition from an 'open' state (apo structure) to a 'closed' state (holo structure). Many studies have utilized collections of apo-holo structure pairs to investigate the conformational transitions and critical residues. However, the collection process is usually complicated, varies from study to study and produces a small-scale data set. AH-DB is designed to provide an easy and unified way to prepare such data, which is generated by identifying/mapping molecules in different Protein Data Bank (PDB) entries. Conformational transitions are identified based on a refined alignment scheme to overcome the challenge that many structures in the PDB database are only protein fragments and not complete proteins. There are 746,314 apo-holo pairs in AH-DB, which is about 30 times those in the second largest collection of similar data. AH-DB provides sophisticated interfaces for searching apo-holo structure pairs and exploring conformational transitions from apo structures to the corresponding holo structures.

  14. Alkaline manganese--zinc battery. [2000 Ah, 100 Wh/kg

    Energy Technology Data Exchange (ETDEWEB)

    Naumenko, V.A.; Lyapuntsova, T.G.; Lidorenko, N.S.; Lebedeva, E.S.; Penkova, L.F.; Aleshin, V.N.

    1975-02-12

    The battery described consisted of flat electrodes assembled in a pack. Cathodes were enclosed in perforated metal frames, while the anodes were metal plates coated with zinc. The batteries had capacities of about 2000 Ah and power--weight ratios of 100 Wh/kg and were resistant to shock and vibration. (RWR)

  15. IEEE 802.11ah: A Technology to Face the IoT Challenge.

    Science.gov (United States)

    Baños-Gonzalez, Victor; Afaqui, M Shahwaiz; Lopez-Aguilera, Elena; Garcia-Villegas, Eduard

    2016-11-22

    Since the conception of the Internet of things (IoT), a large number of promising applications and technologies have been developed, which will change different aspects in our daily life. This paper explores the key characteristics of the forthcoming IEEE 802.11ah specification. This future IEEE 802.11 standard aims to amend the IEEE 802.11 legacy specification to support IoT requirements. We present a thorough evaluation of the foregoing amendment in comparison to the most notable IEEE 802.11 standards. In addition, we expose the capabilities of future IEEE 802.11ah in supporting different IoT applications. Also, we provide a brief overview of the technology contenders that are competing to cover the IoT communications framework. Numerical results are presented showing how the future IEEE 802.11ah specification offers the features required by IoT communications, thus putting forward IEEE 802.11ah as a technology to cater the needs of the Internet of Things paradigm.

  16. Narcolepsy and A(H1N1)pdm09 vaccination

    Science.gov (United States)

    van der Most, Robbert; Van Mechelen, Marcelle; Destexhe, Eric; Wettendorff, Martine; Hanon, Emmanuel

    2014-01-01

    Epidemiological data from several European countries suggested an increased risk of the chronic sleep disorder narcolepsy following vaccination with Pandemrix™, an AS03-adjuvanted, pandemic A(H1N1)pdm09 influenza vaccine. Further research to investigate potential associations between Pandemrix™ vaccination, A(H1N1)pdm09 influenza infection and narcolepsy is required. Narcolepsy is most commonly caused by a reduction or absence of hypocretin produced by hypocretin-secreting neurons in the hypothalamus, and is tightly associated with HLA-II DQB1*06:02. Consequently, research focusing on CD4+ T-cell responses, building on the hypothesis that for disease development, T cells specific for antigen(s) from hypocretin neurons must be activated or reactivated, is considered essential. Therefore, the following key areas of research can be identified, (1) characterization of hypothetical narcolepsy-specific auto-immune CD4+ T cells, (2) mapping epitopes of such T cells, and (3) evaluating potential mechanisms that would enable such cells to gain access to the hypothalamus. Addressing these questions could further our understanding of the potential links between narcolepsy and A(H1N1)pdm09 vaccination and/or infection. Of particular interest is that any evidence of a mimicry-based mechanism could also explain the association between narcolepsy and A(H1N1)pdm09 influenza infection. PMID:24342916

  17. Long-Term Cytotoxicity, pH and Dissolution Rate of AH Plus and MTA Fillapex.

    Science.gov (United States)

    Silva, Emmanuel João Nogueira Leal da; Accorsi-Mendonça, Thais; Pedrosa, Ana Carolina; Granjeiro, José Mauro; Zaia, Alexandre A

    2016-01-01

    The aim of the present study was to verify the long-term cytotoxic effects of the MTA Fillapex and to compare them with AH Plus. Dissolution rate and pH were also evaluated. Human osteoblast cells were incubated with elutes of fresh specimens from AH Plus and MTA Fillapex, and with elutes of the same specimens for 4 successive weeks. Elute's pH was evaluated at each time point. A multiparametric cell viability assay was performed. For dissolution rate, ISO methodology was used. The results were analyzed by one-way analysis of variance, complemented with the Tukey post-test (p0.05). After 1 week, AH Plus became non-cytotoxic on all three evaluated parameters. Conversely, MTA Fillapex remained severely and mildly cytotoxic over the entire experimental period (pMTA Fillapex at all time points (p>0.05). The pH of AH Plus was significantly lower than MTA Fillapex at the second and third week (pMTA Fillapex remained cytotoxic after 4 weeks and its cytotoxicity may be related to the high dissolution rate of this material.

  18. Shari’ah-Compliant E-Commerce Models and Consumer Trust

    Directory of Open Access Journals (Sweden)

    Muhammad Kholifatul I Ardiansyah

    2016-07-01

    Full Text Available This study is aimed at finding out the real picture of Shari’ah-compliant E-commerce model and consumer trust in e-commerce today, analyzing its drawbacks, and finding out how they influence each other. Shari'ah-compliant E-commerce model is a model that describes how e-commerce should run in accordance with the provisions of the Shari’ah. Broadly speaking, e-commerce in the perspective of Shari’ah must comply with some rules, namely: 1. the form of the offer and transaction agreement; 2. the transacting parties (buyers and sellers; 3. Objects and prices in the transaction; 4. Free from major prohibitions in transactions. The sample in this study is Indonesian citizen who are consumers of e-commerce. This research uses descriptive and statistical methods with multiple linear regression model. This model is considered relevant and good to be studied in order to enlighten how e-commerce is currently in the perspective of IslamDOI: 10.15408/aiq.v8i2.2913

  19. Data of evolutionary structure change: 1JJWB-2Z3AH [Confc[Archive

    Lifescience Database Archive (English)

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  20. French experience of 2009 A/H1N1v influenza in pregnant women.

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    Grégory Dubar

    Full Text Available BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes, 111 were hospitalized in obstetric or medical wards (moderate outcomes, and 164 were outpatients (mild outcomes. The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%, notably the severe patients (70%, were in the third trimester. Among the severe patients, twenty (50% underwent mechanical ventilation, and eleven (28% were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8 and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively. Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14% were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the

  1. EFSA AHAW Panel (EFSA Panel on Animal Health and Welfare), ECDC (European Centre for Disease Prevention and Control) and EMA (European Medicines Agency), 2013. Scientific Opinion on the possible risks posed by the Influenza A(H3N2v) virus for animal health and its potential spread and implications

    DEFF Research Database (Denmark)

    Bøtner, Anette

    Swine are an important host in influenza virus ecology since they are susceptible to infections with both avian and human influenza A viruses. In 2011 and 2012, clusters of human infection with a swine-origin influenza A(H3N2) variant virus (H3N2v) containing the matrix (M) gene from the 2009 H1N...

  2. Acetylcholine mobilization in a sympathetic ganglion in the presence and absence of 2-(4-phenylpiperidino)cyclohexanol (AH5183)

    Energy Technology Data Exchange (ETDEWEB)

    Cabeza, R.; Collier, B.

    1988-01-01

    The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2-(4-phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13-14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recovery from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183-treated ganglia, as determined by the synthesis of (/sup 3/H)ACh from (/sup 3/H)choline, and this (/sup 3/H)ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh, and thus we conclude that ACh synthesized in the presence of AH5183 is a releasable as pre-existing ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with (/sup 3/H)choline) and that synthesized during recovery from the drug's effects (perfusion with (/sup 14/C)choline: the ratio of (/sup 3/H)ACh to (/sup 14/C)ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183-induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183-blocked ganglia, even in the drug's continued presence. Venom-induced release of ACh from AH5183-treated ganglia was not less than the venom-induced release from tissues not exposed to AH5183.

  3. Impact of obesity in patients infected with 2009 influenza A(H1N1).

    Science.gov (United States)

    Díaz, Emili; Rodríguez, Alejandro; Martin-Loeches, Ignacio; Lorente, Leonardo; Del Mar Martín, María; Pozo, Juan Carlos; Montejo, Juan Carlos; Estella, Angel; Arenzana, Ángel; Rello, Jordi

    2011-02-01

    A large proportion of patients infected with 2009 influenza A(H1N1) (A[H1N1]) are obese. Obesity has been proposed as a risk factor influencing outcome in these patients. However, its role remains unclear. We evaluate the outcome of patients who are obese and infected with A(H1N1) in the ICU, determining whether obesity is a risk factor for mortality. This was a prospective, observational, and multicenter study performed in 144 ICUs in Spain. Data were obtained from the Grupo de Trabajo en Enfermedades Infecciosas de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (GTEI/SEMICYUC) registry. Adult patients with A(H1N1) that was confirmed by real-time polymerase chain reaction were included in the analysis. Patients who were obese (BMI > 30) were compared with patients who were nonobese. Cox regression analysis was used to determine adjusted mortality. Differences of P 40). Mechanical ventilation (MV) was more frequently applied in patients who were obese (64% vs 52.4%, P < .01) Patients with obesity remained on MV longer than patients who were nonobese (6.5 ± 10.3 days vs 9.3 ± 9.7 days, P = .02), had longer ICU length of stay (10.8 ± 12.1 days vs 13.7 ± 11.7 days, P = .03), and had longer hospitalization (18.2 ± 14.6 days vs 22.2 ± 16.5 days, P = .02). Mortality adjusted by severity and potential confounders identified that obesity was not significantly associated with ICU mortality (hazard ratio, 1.1; 95% CI, 0.69-1.75; P = .68). In our cohort, patients who were obese and infected with A(H1N1) did not have increased mortality. However, there was an association between obesity and higher ICU resource consumption.

  4. PROBLEM PRAKTIK KHURÛJ BAGI ANGGOTA JAMA`AH TABLIGH DI MADURA

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    Faiqoh Bahjah Lailatus Siyami

    2015-07-01

    Full Text Available Khurûj is one of the teachings which is tightly attached to Jama`ah Tabligh that ordered all its followers to go out of the district/area to spread amr al-ma`rûf nahy al-munkar in a certain time. The main problem is when the khurûj obligation is faced to Family obligation. Those obligations can create problems when the member of the Jama`ah Tabligh cannot make the obligation to the family and the khurûj obligation balance. One of the examples is the divorce of the member of the Jama`ah Tabligh. The reason of the divorce is because the lack of living cost when the husband did the khurûj. To fulfill it, the wife gets debt from other people and she cannot pay it off. Doing the khurûj is an activity of Jama`ah Tabligh, where a member will be stated as a legal member when he has joined the khurûj. Khurûj concept in its application is devided into 3 phases. The First is 3 days in a month; the second is 40 days in a year, and the last is 4 months in a lifetime. But the theory of the counting is using unknown and unclear base either from Al-Qur’an and al-Sunnah or any other methods of dakwah that applied by Rasulullah. While Jama`ah Tabligh uses Saying from Al-Qur’an as theoretical foundation about khurûj, that is the word “ukhrijat” containing in QS. Ali Imran (3: 110

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

    Science.gov (United States)

    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.

  6. Simplified large-scale Sanger genome sequencing for influenza A/H3N2 virus.

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    Hong Kai Lee

    Full Text Available BACKGROUND: The advent of next-generation sequencing technologies and the resultant lower costs of sequencing have enabled production of massive amounts of data, including the generation of full genome sequences of pathogens. However, the small genome size of the influenza virus arguably justifies the use of the more conventional Sanger sequencing technology which is still currently more readily available in most diagnostic laboratories. RESULTS: We present a simplified Sanger-based genome sequencing method for sequencing the influenza A/H3N2 virus in a large-scale format. The entire genome sequencing was completed with 19 reverse transcription-polymerase chain reactions (RT-PCRs and 39 sequencing reactions. This method was tested on 15 native clinical samples and 15 culture isolates, respectively, collected between 2009 and 2011. The 15 native clinical samples registered quantification cycle values ranging from 21.0 to 30.56, which were equivalent to 2.4×10(3-1.4×10(6 viral copies/µL of RNA extract. All the PCR-amplified products were sequenced directly without PCR product purification. Notably, high quality sequencing data up to 700 bp were generated for all the samples tested. The completed sequence covered 408,810 nucleotides in total, with 13,627 nucleotides per genome, attaining 100% coding completeness. Of all the bases produced, an average of 89.49% were Phred quality value 40 (QV40 bases (representing an accuracy of circa one miscall for every 10,000 bases or higher, and an average of 93.46% were QV30 bases (one miscall every 1000 bases or higher. CONCLUSIONS: This sequencing protocol has been shown to be cost-effective and less labor-intensive in obtaining full influenza genomes. The constant high quality of sequences generated imparts confidence in extending the application of this non-purified amplicon sequencing approach to other gene sequencing assays, with appropriate use of suitably designed primers.

  7. A novel role of the aryl hydrocarbon receptor (AhR in centrosome amplification - implications for chemoprevention

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    Chatterjee Payel

    2010-06-01

    Full Text Available Abstract Background Centrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation of cyclin/cyclin-dependent kinase 2 (CDK2 activity has previously been shown to be critically involved in centrosome overduplication. We therefore test here whether small molecule CDK inhibitors derived from the bis-indole indirubin can be used to suppress centrosome aberrations as a novel approach to chemoprevention of malignant progression. Results As expected, we found that the CDK inhibitor indirubin-3'-oxime (IO suppresses centrosome amplification in breast cancer cells. However, we made the unexpected discovery that indirubin-derived compounds that have been chemically modified to be inactive as kinase inhibitors such as 1-methyl-indirubin-3'-oxime (MeIO still significantly reduced centrosome amplification. All indirubins used in the present study are potent agonists of the aryl hydrocarbon receptor (AhR, which is known for its important role in the cellular metabolism of xenobiotics. To corroborate our results, we first show that the coincidence of nuclear AhR overexpression, reflecting a constitutive activation, and numerical centrosome aberrations correlates significantly with malignancy in mammary tissue specimens. Remarkably, a considerable proportion (72.7% of benign mammary tissue samples scored also positive for nuclear AhR overexpression. We furthermore provide evidence that continued expression of endogenous AhR is critical to promote centriole overduplication induced by cyclin E and that AhR and cyclin E may function in the same pathway. Overexpression of the AhR in the absence of exogenous ligands was found to rapidly disrupt centriole duplication control. Nonetheless, the AhR agonists IO and MeIO were still found to significantly reduce centriole overduplication stimulated by ectopic AhR expression. Conclusions Our results indicate that

  8. Pandemic influenza A(H1N1) 2009: molecular characterisation and duration of viral shedding in intensive care patients in Bordeaux, south-west France, May 2009 to January 2010.

    Science.gov (United States)

    Malato, L; Llavador, V; Marmier, E; Youssef, J; Balick Weber, C; Rozé, H; Bessede, E; Fleury, H J

    2011-01-27

    From May 2009 to January 2010, the Virology Laboratory at the University Hospital of Bordeaux received more than 4,000 nasopharyngeal samples from the Aquitaine region (south-west France) for the diagnosis of pandemic influenza A(H1N1)2009. Eighty-three infected patients deteriorated and were admitted to intensive care units. Our study focused on 24 of these patients. Positivity for influenza A(H1N1)2009 was monitored by realtime PCR and duration of viral shedding was determined. The first available sample of each patient was analysed for bacterial, fungal and viral co-infection. We observed six bacterial (or bacterial/fungal) co-infections and one viral co-infection with respiratory syncytial virus. The samples were analysed for the presence of the neuraminidase H275Y (N1 numbering) mutation, which confers resistance to oseltamivir, by realtime PCR of the neuraminidase gene. No H275Y mutation was observed in any of the viral strains screened in this study. In parallel, a fragment of the haemagglutinin gene encoding amino acid residues 173 to 362 was sequenced to detect mutations that had been reported to increase the severity of the disease. Two patients were infected by strains bearing the D222G (H3 numbering) mutation. The viral shedding of A(H1N1)2009 in this study ranged from four to 28 days with a median of 11 days.

  9. Effectiveness of the influenza a(H1N1)PDM09 vaccine in adults recommended for annual influenza vaccination : A case-control study

    NARCIS (Netherlands)

    Gefenaite, Giedre; Tacken, Margot; Bos, Jens; Stirbu-Wagner, Irina; Korevaar, Joke C.; Stolk, Ronald P.; Wolters, Bert; Bijl, Marc; Postma, Maarten J.; Wilschut, Jan; Nichol, Kristin L.; Hak, Eelko

    2012-01-01

    Background: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we aimed to assess the effectiveness of MF59-adjuvanted A(H1N1)pdm09 vaccine in a matched case-control study. Objectives: We aimed to assess the effectiveness of MF59- adjuvanted A(H1N1)pdm09 infl

  10. Pengaruh Sistem Waralaba Terhadap Retail Kecil Di Ponorogo Tinjauan Maṣlaḥah

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    Siti Wulandari

    2016-05-01

    Full Text Available Abstract: One of the indications of the acceleration of economic progress in Ponorogo is the rapid development of the real sectors, especially the proliferation of modern businesses using the franchise system. Therefore, small retail businesses today are facing new competitors with huge capital and reliability of modern management. This study tries to find out the impact of the franchise system invasion to the existence of small retails, and how it affects the maṣlaḥah (safety of small retails in Ponorogo. This study uses the theory of maqāṣid al-sharīah in the aspects of ḥifẓ al-māl to analyze the sustainability of small retail businesses amid the proliferation of franchise businesses. Maṣlāḥah is thinking about the advantages and disadvantages on the basis of religious teachings by thinking about priorities and side with the community (al-maṣlaḥah al-'āmah. The results of this study found out the threat of franchise trading system to the existence of small retails. Therefore, the maṣlaḥah for small retail of businesses means the realization of the safety from the expansion of large investors, such as monopoly. Abstrak: Salah satu indikator meningkatnya laju perekonomian Kabupaten Ponorogo ditandai dengan pesatnya perkembangan sektor riil terutama dengan menjamurnya berbagai jenis toko-roko modern (khususnya dengan sistem waralaba yang terus bertambah jumlahnya. Lalu bagaimana dengan para pebisnis retail kecil yang kebanyakan mereka memiliki usaha dengan modal yang tidak terlalu besar. Penelitian ini berupaya mengetahui adakah  pengaruh yang terjadi akibat adanya toko-toko dengan sistem waralaba terhadap eksistensi retail kecil, serta adakah pengaruhnya terhadap kemaslahatan retail kecil yang ada di Ponorogo. Penelitian ini menggunakan teori keberlangsungan usaha yang dikaitkan dengan maqāsid al-shar’īah  aspek kemaslahatan hifz al-māl untuk menguji pengaruh kemaslahatan retail kecil dengan adanya bisnis

  11. Suggestions to the media to help us cope with the A/H7N9 crisis in China.

    Science.gov (United States)

    Sun, Yang; Lu, Hongzhou

    2014-04-01

    The A/H7N9 avian influenza virus sparked global concerns about public health. The media published numerous reports about emerging infectious diseases, including their clinical characteristics and genomic information. However, outbreaks of A/H7N9 posed a real challenge to China's emergency management and especially its dealing with the media. This study analyzes ways to deal with the media during A/H7N9 crises and it proposes a shift in public emergency management from an "Impact-Responsive" approach to a "Prevention-Active" approach. A "Prevention-Active" approach should be used when dealing with the media during subsequent outbreaks.

  12. [A(H5N1) and A(H7N9) avian influenza: the H7N9 avian influenza outbreak of 2013].

    Science.gov (United States)

    Wang, Quan; Yao, Kai-Hu

    2013-06-01

    influenza virus can infect humans and cause disease. The clinical presentation of human infection is usually mild, but the infection caused by A(H5N1) avian influenza virus occurring initially in Hongkong in 1997 or the A(H7N9) virus isolated first at the beginning of this year in China is severe and characterized by high mortality. The mortality rate of adolescents and children caused by H5N1 avian influenza is lower than that of adults and the younger the child the lower the mortality rate. A few pediatric H7N9 avian influenza cases recovered soon after treatment. A child was determined to be a H7N9 avian influenza virus carrier. These findings suggested that the pediatric H7N9 avian influenza infection was mild. It is very important to start anti-virus treatment with oseltamivir as early as possible in cases of avian influenza infection is considered. Combined therapy, including respiratory and circulatory support and inhibiting immunological reaction, is emphasized in the treatment of severe cases.

  13. Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses.

    Science.gov (United States)

    Chen, Haifen; Zhou, Xinrui; Zheng, Jie; Kwoh, Chee-Keong

    2016-12-05

    The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.

  14. BANK SYARÎ'AH DAN TAKÂFUL (Sebuah Kajian Evaluatif-Reflektif atas Perkembangan Bank Syarî'ah dan Takâful di Indonesia

    Directory of Open Access Journals (Sweden)

    Sofyan Hadi

    2014-10-01

    Full Text Available Islam menjiwai dan mewarnai perilaku manusia dalam berpikir,bersikap maupun bertindak dengan batas-batas yang telah ditetapkan, dalam rangka pengabdian kepada Allah swt. Setelahmelalui perdebatan sengit selama berabad-abad tentangperilaku bunga uang (ribâ, interest dalam menentukan perilakuekonomi manusia, antara diharamkan atau dibolehkan, kinimuncul di hadapan kita keputusan di mana terbuka jalan bagiyang mengharamkan bunga dan bagi yang membolehkan ataubahkan mengharuskannya dengan konsep yang lebih Islâmîdan dapat diterima oleh berbagai pihak terutama mayoritaspenduduk Indonesia yang notabene beragama Islam dengan apayang dikenal sebagai bank syarî'ah dan takâful (asuransi Islâm.Melalui kedua lembaga inilah kita berharap dapat menyaksikanpada satu saat terwujudnya “gurita” ekonomi umat yangdahsyat, apabila terjadi kerjasama mudlarabah di tingkatkelembagaan ekonomi syarî'ah (BMI, BSI, BPRS, BMT dan STIdengan berpedoman pada ta’âwanû ‘alâ al-birr wa al-taqwâ, wa lâta'âwanû alâ al-itsm wa al-‘udwân. Kerjasama ini hendaklahprofesional. Untuk itu perlu dibangun manajemen yang Islâmî,yang didukung dengan sumber daya terampil, yang bekerjadengan keyakinan dan teguh dalam pendirian serta memilikimoral atau akhlaq yang luhur.

  15. ANALISIS POTENSI PENERIMAAN KUALITAS ALUMNI PROGRAM STUDI EKONOMI SYARI’AH STAIN KUDUS DITINJAU DARI PERSPEKTIF STAKEHOLDER

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    Ekawati Rahayu Ningsih

    2015-03-01

    Full Text Available GRADUATES RECEPTION QUALITYANALYSIS OF THE POTENTIAL ECONOMIC STUDIES SYARI’AH IN STAIN KUDUS VIEWED FROM THE PERSPECTIVE STAKEHOLDER. The first aim of  this study was to determine the potential reception of  graduates quality in Shariah Economic Studiesof  STAINKudus in the world of  work. Second, to determine the motivations and needs of  stakeholders on the acceptance of  the quality of  graduates in Economics   Shariah STAIN Kudus.And third, to determine what factors which are supporting and inhibiting the absorption of graduates of the Department of Shariah Economics STAIN Kudus in working world. The theory that was developed as a basis for the analysis is the pyramid theory of  motivation and needs of  Abraham Maslow. By using qualitative research approach, the analysis and discussion of this study are:First, the potential acceptance of  Shariah Economy graduates in the working world, especially in the banking and financial institutions Shari’ah is still very large and potentially growing along with the rapid growth in the number of  banking and financial institutions Shari’ah in Indonesia. Second, motivation and needs of  stakeholders for the graduates reception of Shariah Economic STAIN Kudus is because it is the only college in the state of  religion around the Pantura area having Shariah Economic Studies Program and easily accessible. In addition, in order to establish a more synergistic relationship with the STAIN kudus then either the shari’a banking and financial institutions are willing to accept graduates of  Shariah Economic Studies Program as employees, of course, with the various criteria established in the job requirements. Keywords:Potential,  Quality  Admissions,  Graduates, Economic Shariah, Stakeholder. Tujuan penelitian ini adalah: Pertama, untuk mengetahui potensi penerimaan kualitas alumni Program Studi Ekonomi Syari’ah STAIN Kudus di dunia kerja. Kedua, untuk mengetahui motivasi dan

  16. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10−8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID:26379185

  17. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    Directory of Open Access Journals (Sweden)

    M. Rocas

    2011-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs and related halogenated aromatic hydrocarbons (e.g., PCDFs, often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR. Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region, previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age. We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  18. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers.

    Science.gov (United States)

    Rocas, M; Jakubauskiene, E; Kanopka, A

    2011-11-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and related halogenated aromatic hydrocarbons (e.g., PCDFs), often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR). Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region), previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age). We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  19. Detecting Polychlorinated Biphenyls by Ah Receptor and Fluorescence Quantitative PCR with Exonuclease

    Science.gov (United States)

    Zhao, Xiaoxiang; Zhuang, Huisheng

    2010-11-01

    Tetrachlorobiphenyls as ligands were cultivated with goldfish, Ah receptors were extracted from the liver of goldfish and purified by hydroxyapatite. The complex of TCB ligands-receptors were analyzed by Surface Plasmon Resonance. DNA probes were amplified by PCR using Primers F1 and F2 with the DNA recognition site of responsive enhancer. DNA probes bound to the complex were not digested by exonuclease. The DNA that bound to the complex was quantified by real time PCR. A standard curve with TCB concentration to Ct values was obtained in the range of 10-12mol/L to 10-8 mol/L, according to TCB concentration in samples. The detection limit of the assay was below 10-12mol/L of TCB. Compared with HPLC, this assay is much more sensitive. These results suggest that fluorescence quantitative PCR with exonuclease by Ah receptors fits for detection of trace PCB.

  20. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...... and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17...... during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection...

  1. Metapopulation dynamics enable persistence of influenza A, including A/H5N1, in poultry.

    Science.gov (United States)

    Hosseini, Parviez Rana; Fuller, Trevon; Harrigan, Ryan; Zhao, Delong; Arriola, Carmen Sofia; Gonzalez, Armandoe; Miller, Matthew Joshua; Xiao, Xiangming; Smith, Tom B; Jones, Jamie Holland; Daszak, Peter

    2013-01-01

    Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified.

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

    Science.gov (United States)

    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.

  3. Generation and Characterization of Live Attenuated Influenza A(H7N9) Candidate Vaccine Virus Based on Russian Donor of Attenuation

    Science.gov (United States)

    Shcherbik, Svetlana; Pearce, Nicholas; Balish, Amanda; Jones, Joyce; Thor, Sharmi; Davis, Charles Todd; Pearce, Melissa; Tumpey, Terrence; Cureton, David; Chen, Li-Mei; Villanueva, Julie; Bousse, Tatiana L.

    2015-01-01

    Background Avian influenza A (H7N9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV) are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV) to provide temperature sensitive, cold-adapted and attenuated phenotypes. Methodology/Principal Findings LAIV candidate A/Anhui/1/2013(H7N9)-CDC-LV7A (abbreviated as CDC-LV7A), based on the Russian MDV, A/Leningrad/134/17/57 (H2N2), was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering) in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9)RG-LV1 and A(H7N9)RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9) virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7. Conclusions/Significance Our data indicate that the A/Anhui/1/2013(H7N9)-CDC-LV7A reassortant virus is a safe and

  4. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  5. The five AhMTP1 zinc transporters undergo different evolutionary fates towards adaptive evolution to zinc tolerance in Arabidopsis halleri.

    Directory of Open Access Journals (Sweden)

    Zaigham Shahzad

    2010-04-01

    Full Text Available Gene duplication is a major mechanism facilitating adaptation to changing environments. From recent genomic analyses, the acquisition of zinc hypertolerance and hyperaccumulation characters discriminating Arabidopsis halleri from its zinc sensitive/non-accumulator closest relatives Arabidopsis lyrata and Arabidopsis thaliana was proposed to rely on duplication of genes controlling zinc transport or zinc tolerance. Metal Tolerance Protein 1 (MTP1 is one of these genes. It encodes a Zn(2+/H(+ antiporter involved in cytoplasmic zinc detoxification and thus in zinc tolerance. MTP1 was proposed to be triplicated in A. halleri, while it is present in single copy in A. thaliana and A. lyrata. Two of the three AhMTP1 paralogues were shown to co-segregate with zinc tolerance in a BC1 progeny from a cross between A. halleri and A. lyrata. In this work, the MTP1 family was characterized at both the genomic and functional levels in A. halleri. Five MTP1 paralogues were found to be present in A. halleri, AhMTP1-A1, -A2, -B, -C, and -D. Interestingly, one of the two newly identified AhMTP1 paralogues was not fixed at least in one A. halleri population. All MTP1s were expressed, but transcript accumulation of the paralogues co-segregating with zinc tolerance in the A. halleri X A. lyrata BC1 progeny was markedly higher than that of the other paralogues. All MTP1s displayed the ability to functionally complement a Saccharomyces cerevisiae zinc hypersensitive mutant. However, the paralogue showing the least complementation of the yeast mutant phenotype was one of the paralogues co-segregating with zinc tolerance. From our results, the hypothesis that pentaplication of MTP1 could be a major basis of the zinc tolerance character in A. halleri is strongly counter-balanced by the fact that members of the MTP1 family are likely to experience different evolutionary fates, some of which not concurring to increase zinc tolerance.

  6. Emergence of Islamic Sciences in Merv (First Two Centuries A.H.

    Directory of Open Access Journals (Sweden)

    Mesut CAN

    2016-12-01

    Full Text Available Merv, the first center and one of the four largest cities of Khorasan, had undergone some radical changes, which also influenced the history of the region it was located, in political, military, social, cultural and scientific aspects since its conquest. In this context, the emergence of Islamic sciences in Merv and its status in the first two centuries a.h. will be handled and some scientific personalities of the period will be mentioned within the scope of the article.

  7. 松下4 Ah 18650型锂离子电池

    Institute of Scientific and Technical Information of China (English)

    贾旭平

    2010-01-01

    @@ 2009年12月,松下发布了一款可用于多种便携式设备的"18650"尺寸的锂离子充电电池的高性能产品,型号为NCR18650A.与原产品"NCR18650"相比,容量从2.9 Ah提高到了3.1 Ah.

  8. Analysis of a pandemic in the Italian newspapers: the A(H1N1 experience

    Directory of Open Access Journals (Sweden)

    Alessandro Zanetti

    2012-06-01

    Full Text Available

    Background: in 2009 a novel infective agent, a(H1n1, was recognized by the World Health organization (WHo as a pandemic virus. Like most European countries, Italy experienced a single pandemic wave during fall-winter 2009. The objective of our study was to evaluate the news reports and the representation of the a(H1n1 pandemic in the Italian newspapers both quantitatively and qualitatively.

    Methods: from april 24th, 2009 to February 28th, 2010, seven national newspapers were monitored for the quantitative reporting of a(H1n1. In a three month sample period, reports were evaluated quali- tatively by considering their front page presence, tones used for headlines, and images and figures dedicated to the topic.

    Results: in a ten month window, a total of 1220 articles were published. The reporting period showed four peaks and one hollow, with a similar pattern for all the newspapers. during the three-month sample period, we found a total of 382 articles, 98.4% of which appeared on front pages, 33.8% of which contained headlines using alarming tones, and 47.8% which contained info-graphic elements.

    Conclusions: the a(H1n1 2009 pandemic in Italy was mild; nonetheless, newspapers devoted great attention to the new influenza and used alarmist tones. In similar situations, there are several areas where scientists should play a greater role. scientists should support journalists in understanding scientific issues and help them translate scientific information into news items. scientists should also help to contain the anxiety aroused in lay people by a pandemic, and support vaccination efforts dedicated to it....

  9. Lithium-Ion Performance and Abuse Evaluation Using Lithium Technologies 9Ah cell

    Science.gov (United States)

    Hall, Albert Daniel; Jeevarajan, Judith A.

    2006-01-01

    Lithium-ion batteries in a pouch form offer high energy density and safety in their designs and more recently they are offering performance at higher rates. Lithium Technologies 9Ah high-power pouch cells were studied at different rates, thermal environments, under vacuum and several different conditions of abuse including overcharge, over-discharge and external short circuit. Results of this study will be presented.

  10. PENGUNGKAPAN SYARI’AH COMPLIANCE DAN KEPATUHAN BANK SYARIAH TERHADAP PRINSIP SYARIAH

    Directory of Open Access Journals (Sweden)

    Asrori -

    2012-03-01

    Full Text Available Penelitian ini bertujuan mengukur niat para akuntan dan manager bank Islam untuk menerapkan praktek pengungkapan kepatuhan shariah sebagai tanggung jawab kepatuhan terhadap prinsip-prinsip bank Islam dilihat dari perspektif teori tindakan. Populasi untuk penelitian ini adalah para akuntan dan manager cabang bank Islam di kota Semarang dimana untuk respondennya berjumlah 36. Data dianalisis dengan menggunakan linear regression. Hasil dari penelitian ini untuk memberikan dukungan empiris terhadap teori tindakan dan juga untuk memprediksi niat para akuntan dan manager bank Islam untuk menerapkan praktek pengungkapan kepatuhan shariah. Praktek pengungkapan kepatuhan shariah disarankan untuk diterapkan pada pelaporan keuangan sebagai tanggung jawab kepatuhan bank Islam. This study aims to assess the intentions of accountants and managers of Islamic banks to apply the disclosure practices of syari’ah compliance as accountability for adherence to the principles of syari’ah Islamic banks in the perspective of the theory of reasoned action. The study population include accountants and managers of Islamic bank branches in the city of Semarang in which there are 36 respondents. Linear regression was implemented for analyzing the data to test the hypothesis used. The results of this study provide empirical support for the theory of reasoned action. Then, it can also be used to predict the intentions of accountants and managers of Islamic banks to apply the disclosure practices of syari’ah compliance. Syari’ah compliance disclosure practices is suggested to be applied in financial report as a compliance responsibility of Islamic banks.

  11. INVESTIGATION ON HOT DUCTILITY AND STRENGTH OF CONTINUOUS CASTING SLAB FOR AH32 STEEL

    Institute of Scientific and Technical Information of China (English)

    G.Y. Li; X.F. Li; L.G. Ao

    2006-01-01

    By means of Gleeble-1500 testing machine, the simulation of continuous casting process for AH32 steel was carried out and hot ductility and strength were determined. The cracking sensitivity was studied under the different temperatures and strain rates. The Precipitations of AlN at different temperatures and the fractures of high-temperature tensile samples were observed by using TEM (transmission electron microscope) and SEM (scanning electron microscope). The factors affecting the brittle temperature zone were discussed.

  12. AH-DB: collecting protein structure pairs before and after binding

    OpenAIRE

    2011-01-01

    This work presents the Apo–Holo DataBase (AH-DB, http://ahdb.ee.ncku.edu.tw/ and http://ahdb.csbb.ntu.edu.tw/), which provides corresponding pairs of protein structures before and after binding. Conformational transitions are commonly observed in various protein interactions that are involved in important biological functions. For example, copper–zinc superoxide dismutase (SOD1), which destroys free superoxide radicals in the body, undergoes a large conformational transition from an ‘open’ st...

  13. Corporate Governance in Shareholding Companies: Comparing Legal Perspective and Position of Shari’ah

    Directory of Open Access Journals (Sweden)

    Aznan, H.

    2015-12-01

    Full Text Available This study examines the concept of corporate governance in shareholding companies and the legal perspective in comparison with the position of Shari’ah. The purpose of governance is to instil confidence among the stakeholders that the Boards of Directors are applying a diligent legal and administrative framework, to avoid potential administrative and financial failures and corruption. The study has proceeded by defining the concept of governance from linguistics, accounting, administrative, and legal perspectives. The study also discusses the stands of international organisations on the issue of corporate governance. Then, it is proceeded by discussing the concept of corporate governance from Shari’ah point of view. The study found that even with the absence of the term “company governance” in Islamic Law, the concept of corporate governance is in line with the Shari’ah and that their scholars have clearly referred to it in their literature. The study has used the descriptive, analytical, inductive and comparative methodology in analyzing the subject matter.

  14. BAGI HASIL DAN BANK SYARI’AH (Solusi terhadap Bunga Bank

    Directory of Open Access Journals (Sweden)

    Rudy Haryanto Rudy Haryanto

    2012-07-01

    Full Text Available Abstract: To save money in terms of investation is one of bank’s functions. Interest and production sharing are kinds of investation in banking system. Interest is a marketable entry in conventional banking, however production sharing is known in syari’ah banking system. Some people argue that interest cannot be seperated from the banking activity, in fact Islam recommends the followers to avoid it; hence it could be substituted with term of production sharing. It matches the priciple of musyarakah and mudharabah as being taught by Rasûlullâh SAW. Bank interest is considered ribâ (excessive interest and it is forbidden in Islam. Moreover, production sharing is more useful and beneficial for people. Unfortunately, the value of production sharing (syarî’ah banking product is lower than the value of banking interest (conventional banking product due to the fact that the ralationship established by syari’ah banking and its customer is based on the principle of gotong royong (mutual coorporation and production sharing partnership. Key Words: ribâ, musyarakah, mudharabah, dan bagi-hasil  

  15. [Pilot studies with a serotonin agonist (AH 25086 B). Efficacy and tolerance in acute migraine attacks.].

    Science.gov (United States)

    Doenicke, A; Siegel, E

    1987-07-01

    AH 25086 B is a selective agonist of the newly determined 5-HT(1) receptors, which are sited mainly in the intracranial section of the carotid artery. According to experimental studies, the effect of AH 25086 B is decidedly more highly selective than that of ergotamine; the blood flow through the arteriovenous anastomoses of the internal carotid artery is clearly reduced, while the blood flow through the capillaries supplying the brain is increased. With AH 25086 B administered in an infusion rapid abolition of migraine attacks already in progress proved possible. The first 12 patients worldwide to receive this preparation were treated, some on several occasions, for a total of 21 migraine attacks: 7 received one infusion, 3 received two, 1 three, and 1 patient received five infusions. There were some side-effects with some infusions: nausea (18), vomiting (9), and photophobia (19). On average it took 31 min (range 10-60 min) for the headache to be relieved, regardless of the duration of migraine symptoms before the start of treatment. This was not a controlled study, but the results (14 very good, 6 good or satisfactory, in 21 attacks treated) were better than could have been expected by chance. Tolerance of the preparation was good, all side-effects being transitory and mild; with dosages up to 1.6 mug kg(-1) min(-1) no changes were seen in heart rate or blood pressure.

  16. ATSAR THARIQAH AL-QIRA'AH AL-MUTAKARRIRAH FI MAHARAH AL-KITABAH

    Directory of Open Access Journals (Sweden)

    Rihlah

    2016-06-01

    Full Text Available This study aimed to reveal the students' writing skill, namely dictation (Imlâ’ and to analyze the use of the repeated reading technique in learning Qirâ'ah Jahriyyah, as well as to determine the effect of the use of al-Qirâ'ah al-Mutakarrirah technique on the students' skills in writing dictation. This method was used to improve students’ reading fluency at the beginners’ level, which was popularized by Samuel in 1979. This research used the experimental method through pretest and posttest control group design. The samples of the research were 44 students consisted of 22 students the experimental class and 22 students of the control class. The analysis of the data applied t-test. The results showed that the use of was significant on the students' writing skill in dictation. It was based on the tcount, 2.64, and ttable, 2.02, at the significance level of 5%. The al-Qirâ'ah al-Mutakarrirah technique was thus effectively used to develop the beginner-leveled students’ writing skill, especially dictation.

  17. PERSPEKTIF MUHAMMAD SA‘ÎD AL-ASYMÂWÎ tentang HISTORISITAS SYARI’AH

    Directory of Open Access Journals (Sweden)

    Mutawalli Mutawalli

    2009-06-01

    Full Text Available The Islamic law in Islamic thought tradition is viewed as significant knowledge for development of other Islamic knowledge. However, in an epistemological area, the concept of Islamic law provokes debates in terms of its implementation, for example, whether it is considered syarî‘ah or fiqh? Such question is always raised by contemporary Muslim thinkers like Muhammad Sa‘îd al-Asymâwî.Al-Asymâwî’s question is related to his paradigm that firmly differentiates syarî‘ah (Islamic law as religious teachings and fiqh (religious thoughts. Syarî‘ah is Allah’s ways and methods consisting of values and principles that are flexible following community movement. While fiqh is Muslim scholars’ deduction, exploration and interpretation of Al-Qur’an and Sunnah, it is limited to times and spaces. Consequently, according to such paradigm, some Islamic orders that are considered authoritative by the majority of Muslim scholars should be reviewed such as Islamic inheritance, criminal and political laws. With this approach, Al-Asymâwî is claimed as a real guard of liberalism and secularism among Muslim thinkers.

  18. Examination of design options for 35 Ah ambient temperature Li-TiS sub 2 cells

    Science.gov (United States)

    Shen, D. H.; Rao, S. S.; Yen, S. P. S.; Somoano, R. B.

    1986-01-01

    The Jet Propulsion Laboratory is actively engaged in the development of ambient temperature rechargable lithium cells for future NASA geosynchronous Earth orbit (GEO) missions. To achieve these ambitious goals, Li-TiS2, Li-MoS3, and Li-V6O13 systems were examined in detail. Among these three, the Li-TiS2 system has shown the longest life cycle and highest rate capability. Experimental Li-TiS2 batteries (10.5 V, 0.4 Ah) developed in-house have completed eight simulated and accelerated GEO seasons successfully. Inview of the encouraging results, the design options were examined for a scaled-up Li-TiS2 cell. It is hoped that the results of these studies will provide guidelines for prioritizing the research efforts and guiding the selection of optimized materials. Designs for 35 Ah Li-TiS2 cell were examined because present day geosynchronous satellites are powered by batteries of 35 Ah capacity. A computer program was developed to evaluate the influence of various design parameters on the specific energy and the rate capability of the cells.

  19. UNQUESTIONED GENDER LENS IN CONTEMPORARY INDONESIAN SHARI‘A ORDINANCES (PERDA SYARI’AH

    Directory of Open Access Journals (Sweden)

    Dewi Candraningrum

    2007-08-01

    Full Text Available Indonesian Muslim participation in the democratic arena is now contested with the arrival of the decentralization process in 423 districts since 1992. The most notable movement is the quest for Islamic identity in the rejuvenation of Shari‘ah Ordinances which is interpreted symbolically and transcripturally. These ordinances have unrecognized the importance of gender lens in its practice. Until the end of 2007 no less than 63 districts have ratified Perda Syari’ah. In general, these ordinances designed to govern three aspects of public life, namely (1 to eradicate social crimes especially prostitutions and gambling; (2 to enforce ritual observances among Muslims such as reading the Qur’an, Friday congregations and fasting during Ramadhan; and (3 to govern the way people dress up in public sphere—especially the head-veiling for women. Although Islam is the religion of the majority there are also non-Muslim among Indonesian and institutionally Indonesia is not an Islamic state, therefore the ratification of Perda Syari’ah betrayed national consensus agreed upon by the founding fathers of the republic.

  20. Investigation of a Coupled Arrhenius-Type/Rossard Equation of AH36 Material.

    Science.gov (United States)

    Qin, Qin; Tian, Ming-Liang; Zhang, Peng

    2017-04-13

    High-temperature tensile testing of AH36 material in a wide range of temperatures (1173-1573 K) and strain rates (10(-4)-10(-2) s(-1)) has been obtained by using a Gleeble system. These experimental stress-strain data have been adopted to develop the constitutive equation. The constitutive equation of AH36 material was suggested based on the modified Arrhenius-type equation and the modified Rossard equation respectively. The results indicate that the constitutive equation is strongly influenced by temperature and strain, especially strain. Moreover, there is a good agreement between the predicted data of the modified Arrhenius-type equation and the experimental results when the strain is greater than 0.02. There is also good agreement between the predicted data of the Rossard equation and the experimental results when the strain is less than 0.02. Therefore, a coupled equation where the modified Arrhenius-type equation and Rossard equation are combined has been proposed to describe the constitutive equation of AH36 material according to the different strain values in order to improve the accuracy. The correlation coefficient between the computed and experimental flow stress data was 0.998. The minimum value of the average absolute relative error shows the high accuracy of the coupled equation compared with the two modified equations.

  1. Evaluation of the apical sealing ability of bioceramic sealer, AH plus & epiphany: An in vitro study

    Directory of Open Access Journals (Sweden)

    Suprit Sudhir Pawar

    2014-01-01

    Full Text Available Objective: This in vitro study evaluated and compared the microleakage of three sealers; Endosequence bioceramic (BC sealer, AH Plus and Epiphany. Materials and Methods: Study was done on 75 extracted human single rooted permanent teeth, which were decoronated and the root canals were instrumented. The specimens were randomly divided into three groups (n = 25 and obturated by continuous wave condensation technique. Group A: using Endosequence BC, Group B: using AH Plus sealer, Group C: using Resilon Epiphany system. Microleakage was evaluated using dye penetration method. Teeth were split longitudinally and then horizontally markings were made at 2, 4 and 6 mm from the apex. Dye penetration evaluation was done under stereomicroscope (30X magnification. Results: The dye penetration in Group B was more than in Group A and C in both vertical and horizontal directions, suggesting that newly introduced BC sealer and Epiphany sealer sealed the root canal better compared to AH Plus Sealer. Conclusion: Newer root canal sealers seal the root canal better but cannot totally eliminate leakage.

  2. Regulation of mouse small heat shock protein αb-crystallin gene by aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Shuang Liu

    Full Text Available The stress-inducible small heat shock protein (shsp/αB-crystallin gene is expressed highly in the lens and moderately in other tissues. Here we provide evidence that it is a target gene of the aryl hydrocarbon receptor (AhR transcription factor. A sequence (-329/-323, CATGCGA similar to the consensus xenobiotic responsive element (XRE, called here XRE-like, is present in the αBE2 region of αB-crystallin enhancer and can bind AhR in vitro and in vivo. αB-crystallin protein levels were reduced in retina, lens, cornea, heart, skeletal muscle and cultured muscle fibroblasts of AhR(-/- mice; αB-crystallin mRNA levels were reduced in the eye, heart and skeletal muscle of AhR(-/- mice. Increased AhR stimulated αB-crystallin expression in transfection experiments conducted in conjunction with the aryl hydrocarbon receptor nuclear translocator (ARNT and decreased AhR reduced αB-crystallin expression. AhR effect on aB-crystallin promoter activity was cell-dependent in transfection experiments. AhR up-regulated αB-crystallin promoter activity in transfected HeLa, NIH3T3 and COS-7 cells in the absence of exogenously added ligand (TCDD, but had no effect on the αB-crystallin promoter in C(2C(12, CV-1 or Hepa-1 cells with or without TCDD. TCDD enhanced AhR-stimulated αB-crystallin promoter activity in transfected αTN4 cells. AhR could bind to an XRE-like site in the αB-crystallin enhancer in vitro and in vivo. Finally, site-specific mutagenesis experiments showed that the XRE-like motif was necessary for both basal and maximal AhR-induction of αB-crystallin promoter activity. Our data strongly suggest that AhR is a regulator of αB-crystallin gene expression and provide new avenues of research for the mechanism of tissue-specific αB-crystallin gene regulation under normal and physiologically stressed conditions.

  3. Evaluation of Cross-immune Reaction of Anti-Aeromonas hydrophila AH1 Serum%抗嗜水气单胞菌AH1血清交叉免疫反应的评价

    Institute of Scientific and Technical Information of China (English)

    张丹凤; 陈丽芳; 朱徽

    2010-01-01

    本研究利用嗜水气单胞菌(Aeromonas hydrophila)AH1腹腔注射小白鼠,测定半数致死量LD50为1.35×107.在此基础上制备抗嗜水气单胞菌AH1血清(抗AH1血清),采用凝集反应测出抗AH1血清的效价为25,600.进一步分析抗AH1血清对温和气单胞菌(Aeromonas sobria)等13种致病菌的交叉免疫反应,结果表明,抗AH1血清与气单胞菌属细菌、孤菌属细菌和假单胞属细菌之间的交叉反应程度比较大,而与其它属细菌之间存在的交叉反应程度小,或不存在交叉反应.

  4. Operational effectiveness analyses of AH/UAV cooperative surveillance against mission%基于AH/UAV编队协同侦察打击的作战效能研究

    Institute of Scientific and Technical Information of China (English)

    任鹏; 高晓光

    2011-01-01

    The cooperative combat mission was descripted, and the dynamic mathematical model of the AH/UAV cooperative attacking ground target in the particular threaten environment was established. By simulation analysis, the mission success probability, the target damage probability and the survival probability of the AH/UAV cooperative combat were significantly increased.%对AH/UAV协同作战任务进行了客观描述,建立了AH/UAV编队协同在指定威胁环境条件下对地面重要目标实施攻击的动态数学模型.通过仿真,分析了AH/UAV协同执行侦察打击任务的重要作战效能指标,并通过对比分析可知,AH/UAV协同作战能够显著提高攻击作战的任务成功率和对目标的击毁率,同时能够降低风险,提高自身安全.

  5. A comparison of adrenergic receptors of rat ascites hepatoma AH130 cells with those of normal rat hepatocytes.

    Science.gov (United States)

    Sanae, F; Miyamoto, K; Koshiura, R

    1988-04-01

    The pharmacological specificity of adrenergic receptors in the plasma membrane of rat ascites hepatoma AH130 cells was compared with that in normal rat hepatocytes. The number of [125I]iodocyanopindolol-binding sites was much greater in AH130 cells than in the hepatocytes. We characterized the alpha-adrenergic receptor subtypes using the alpha 1-selective ligand [3H]prazosin and the alpha 2-selective ligand [3H]clonidine. AH130 cells had fewer prazosin-binding sites than the hepatocytes and about 8 times as many clonidine-binding sites of high affinity. The results showed that the adrenergic receptors in AH130 cells have pharmacological properties that are very different from those of the receptors in normal rat hepatocytes.

  6. Determinants of 2009 A/H1N1 influenza vaccination among pregnant women in Hong Kong.

    Science.gov (United States)

    Tarrant, Marie; Wu, Kendra M; Yuen, Carol Yuet Shueng; Cheung, Ka Lun; Chan, Vincci Hiu Sze

    2013-01-01

    During the 2009–2010 A/H1N1 influenza pandemic, pregnant women infected with the virus experienced excess morbidity and mortality when compared with other groups. Once a vaccine was available, pregnant women were a priority group for vaccination. Only a few studies have reported on the uptake of 2009 A/H1N1 influenza vaccine among pregnant women during the pandemic and none were from Asia. The purpose of this study was to examine factors associated with 2009 A/H1N1 influenza vaccine uptake among pregnant women in Hong Kong. Using a multi-center, cross-sectional design, we recruited 549 postpartum women from four post-natal wards in Hong Kong over a 4-month period during the second wave of the A/H1N1 influenza pandemic in the winter and spring of 2010. Only 6.2% (n = 34) of participants had received the 2009 A/H1N1 influenza vaccine and 4.9% (n = 27) had received the seasonal influenza vaccine. The most common reasons for not receiving the 2009 A/H1N1 vaccine were fear of causing harm to themselves or their fetus. A high knowledge level (OR = 19.06; 95% CI 5.55, 65.48), more positive attitudes (OR = 3.52; 95% CI 1.37, 9.07), and having a family member who had the 2009 A/H1N1 influenza vaccine (OR = 7.69; 95% CI 2.92, 20.19) were independently and positively associated with vaccination. Study results show an unacceptably low uptake of the pandemic A/H1N1 influenza vaccine among pregnant women in Hong Kong. Interventions to increase influenza vaccine knowledge and uptake among this group should be a priority for future pandemic planning and seasonal vaccination campaigns.

  7. Pseudomine, an isoxazolidone with siderophoric activity from Pseudomonas fluorescens AH2 isolated from Lake Victorian Nile Perch

    DEFF Research Database (Denmark)

    Anthoni, U.; Christophersen, C.; Nielsen, P.H.

    1995-01-01

    A siderophore, pseudomonine, and sodium salicylate were isolated from the culture broth of iron-deficient cultures of Pseudomonas fluorescens AH2 isolated from the surface of spoiled Nile Perch from Lake Victoria......A siderophore, pseudomonine, and sodium salicylate were isolated from the culture broth of iron-deficient cultures of Pseudomonas fluorescens AH2 isolated from the surface of spoiled Nile Perch from Lake Victoria...

  8. Two fatalities associated with synthetic opioids: AH-7921 and MT-45.

    Science.gov (United States)

    Fels, Helena; Krueger, Julia; Sachs, Hans; Musshoff, Frank; Graw, Matthias; Roider, Gabriele; Stoever, Andreas

    2017-08-01

    In this study, two fatalities associated with the synthetic opioids AH-7921 and MT-45 are reported. Within the last few years, both compounds have emerged on the recreational drug market and are sold as "research chemicals" on the internet. In the first case, a 22-year-old woman was found dead in the bedroom of her apartment by two of her friends. A plastic bag labeled "AH-7921" was found in the apartment and the two friends stated that the deceased had consumed AH-7921 prior to her death. The woman was a known drug addict. In the second case, a 24-year-old man was found dead in his room by his mother. The deceased was sitting on a chair in front of his desk slumped over. Several bags of white powder labeled "MT-45", "Methoxmetamine" and "Methoxphenidine" were found in his room. Toxicological analyses of femoral blood, heart blood, liver, pericardial fluid, urine, vitreous humor and stomach content of the deceased were performed using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Time-of-flight mass spectrometry was carried out on an LC-Triple TOF 5600 system (AB Sciex) with electrospray ionization operated in positive mode. In the first case, additional hair analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-QTOF-MS. In both cases, the relevant synthetic opioid could be detected in all analyzed samples. The concentration of AH-7921 was determined to be 450μg/L in femoral blood. MT-45 was present at a concentration of 2900μg/L in femoral blood. Besides methoxmetamine which could qualitatively be detected in femoral blood, urine and stomach content no methoxphenidine was found. In summary, deaths of the young individuals could be, by exclusion of other causes of death, attributed to the consumption of an overdose of AH-7921 and MT-45, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Comparison of the Roche RealTime ready Influenza A/H1N1 Detection Set with CDC A/H1N1pdm09 RT-PCR on samples from three hospitals in Ho Chi Minh City, Vietnam

    Science.gov (United States)

    Tham, Nguyen thi; Hang, Vu thi Ty; Khanh, Trong Huu; Viet, Do Chau; Hien, Tran Tinh; Farrar, Jeremy; van Vinh Chau, Nguyen; van Doorn, H. Rogier

    2012-01-01

    Background Real-time PCR can be considered the gold standard for detection of influenza viruses due to its high sensitivity and specificity. Roche has developed the RealTime ready Influenza A/H1N1 Detection Set, consisting of a generic influenza virus A PCR targeting the M2 gene (M2 PCR) and a specific PCR targeting the HA of A/H1N1-pdm09 (HA PCR, 2009 H1N1), with the intention to make a reliable, rapid, and simple test to detect and quantify 2009 H1N1 in clinical samples. Methods We evaluated this kit against the USCDC/WHO real-time PCR for influenza virus using 419 nose and throat swabs from 210 patients collected in 3 large hospitals in Ho Chi Minh city, Vietnam. Results In the per patient analysis, when compared to CDC PCR, the sensitivity and specificity of the M2 PCR were 85.8 and 97.6%, respectively; the sensitivity and specificity of HA PCR were 88.2 and 100%, respectively. In the per sample analysis, the sensitivity and specificity in nose swabs were higher than in throat swabs for both M2 and HA PCRs. The viral loads as determined with the M2 and HA PCRs correlated well with the Ct values of the CDC PCR. Conclusion Compared with the CDC PCR, the kit has a reasonable sensitivity and very good specificity for the detection and quantification of Influenza A virus and A/H1N1-pdm09. However, given the current status of 2009 H1N1, a kit that can detect all circulating seasonal influenza viruses would be preferable. PMID:22785431

  10. In Vitro Cytotoxicity of GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex.

    Science.gov (United States)

    Saygili, Gokhan; Saygili, Suna; Tuglu, Ibrahim; Davut Capar, Ismail

    2017-01-01

    The aim of the present in vitro study was to evaluate the cytotoxicity of different sealers including GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex on L929 murine fibroblasts. Samples of GuttaFlow Bioseal, GuttaFlow 2, AH-Plus and MTA Fillapex were fabricated in Teflon disks of 5 mm diameter and 3 mm thickness. L929 fibroblasts were exposed to the extracts of these materials for 3, 24, 72 and 168 h at 37(°)C with 5% CO2. Cell viability was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The data were analysed by ANOVA. GuttaFlow Bioseal was nontoxic at all experimental time points (P>0.05), whereas MTA Fillapex and AH-Plus were toxic (PMTA Fillapex was more cytotoxic than AH-Plus. There were more apoptotic cells in the MTA Fillapex and AH-Plus groups than in the other groups at 3 h (PMTA Fillapex and AH-Plus. At all experimental time points, there was no significant difference in the cell viability between the GuttaFlow Bioseal group and the control group.

  11. EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) - development of e-research platform

    Science.gov (United States)

    Orlecka-Sikora, Beata

    2017-04-01

    TCS AH is based on IS-EPOS Platform. The Platform facilitates research on anthropogenic hazards and is available online, free of charge https://tcs.ah-epos.eu/. The Platform is a final product of the IS-EPOS project, founded by the national programme - POIG - which was implemented in 2013-2015 (POIG.02.03.00-14-090/13-00). The platform is a result of a joint work of scientific community and industrial partners. Currently, the development of TCS AH is carried under EPOS IP project (H2020-INFRADEV-1-2015-1, INFRADEV-3-2015). Platform is an open virtual access point for researchers and Ph. D. students interested in anthropogenic seismicity and related hazards. This environment is designed to ensure a researcher the maximum possible liberty for experimentation by providing a virtual laboratory, in which the researcher can design own processing streams and process the data integrated on the platform. TCS AH integrates: data and specific high-level services. Data gathered in the so-called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which, under certain circumstances can become hazardous for people, infrastructure and the environment. 7 sets of seismic, geological and technological data were made available on the Platform. The data come from Poland, Germany, UK and Vietnam, and refer to underground mining, reservoir impoundment, shale gas exploitation and geothermal energy production. The next at least 19 new episodes related to conventional hydrocarbon extraction, reservoir treatment, underground mining and geothermal energy production are being integrated within the framework of EPOS IP project. The heterogeneous multi-disciplinary data (seismic, displacement, geomechanical data, production data etc.) are transformed to unified structures to form integrated and validated datasets. To deal with this various data the problem-oriented services were designed and implemented. The particular attention

  12. Identification and characterization of a gene encoding a putative lysophosphatidyl acyltransferase from Arachis hypogaea

    Indian Academy of Sciences (India)

    Si-Long Chen; Jia-Quan Huang; Lei Yong; Yue-Ting Zhang; Xiao-Ping Ren; Yu-Ning Chen; Hui-Fang Jiang; Li-Ying Yan; Yu-Rong Li; Bo-Shou Liao

    2012-12-01

    Lysophosphatidyl acyltransferase (LPAT) is the important enzyme responsible for the acylation of lysophosphatidic acid (LPA), leading to the generation of phosphatidic acid (PA) in plant. Its encoding gene is an essential candidate for oil crops to improve oil composition and increase seed oil content through genetic engineering. In this study, a full-length AhLPAT4 gene was isolated via cDNA library screening and rapid amplification of cDNA ends (RACE); our data demonstrated that AhLPAT4 had 1631 nucleotides, encoding a putative 43.8 kDa protein with 383 amino acid residues. The deduced protein included a conserved acyltransferase domain and four motifs (I–IV) with putative LPA and acyl-CoA catalytic and binding sites. Bioinformatic analysis indicated that AhLPAT4 contained four transmembrane domains (TMDs), localized to the endoplasmic reticulum (ER) membrane; detailed analysis indicated that motif I and motifs II–III in AhLPAT4 were separated by the third TMD, which located on cytosolic and ER luminal side respectively, and hydrophobic residues on the surface of AhLPAT4 protein fold to form a hydrophobic tunnel to accommodate the acyl chain. Subcellular localization analysis confirmed that AhLPAT4 was a cytoplasm protein. Phylogenetic analysis revealed that AhLPAT4 had a high homology (63.7–78.3%) with putative LPAT4 proteins from Glycine max, Arabidopsis thaliana and Ricinus communis. AhLPAT4 was ubiquitously expressed in diverse tissues except in flower, which is almost undetectable. The expression analysis in different developmental stages in peanut seeds indicated that AhLPAT4 did not coincide with oil accumulation.

  13. Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection

    Science.gov (United States)

    Qin, Ying; Horby, Peter W.; Tsang, Tim K.; Chen, Enfu; Gao, Lidong; Ou, Jianming; Nguyen, Tran Hien; Duong, Tran Nhu; Gasimov, Viktor; Feng, Luzhao; Wu, Peng; Jiang, Hui; Ren, Xiang; Peng, Zhibin; Li, Sa; Li, Ming; Zheng, Jiandong; Liu, Shelan; Hu, Shixiong; Hong, Rongtao; Farrar, Jeremy J.; Leung, Gabriel M.; Gao, George F.; Cowling, Benjamin J.; Yu, Hongjie

    2015-01-01

    Background. The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. Methods. We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). Results. We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). Conclusions. The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1. PMID:25940354

  14. TRANSFORMATION OF MAQÂSHID Al-SYARÎ’AH (An Overview of the Development of Islamic Law in Indonesia

    Directory of Open Access Journals (Sweden)

    Absori .

    2016-07-01

    Full Text Available Abstract:This study is part of an effort to systematize the basic conception of the values of the sharia as the foundation in the life of nation and state life, where the orientation is to embody the essence of the religious life through the maqâshid al-syarî`ah. Islam as al-dîn has been providing the basics of life of Muslims through the al-Qur’an and as-Sunnah. Both of these contain guidance values of human life, including in running the sharia for Muslims. Sharia (syarî`ah in perspective of terminology is "street". In an isthilâhî perspective, it is a way to get to God. The basic meaning of sharia itself should be realized in the basic understanding maqâshid al-syarî`ah, which can be interpreted within the scope of statehood, because the meaning contained are the values of universality of maqâshid al-syarî`ah. In the context of Indonesian, then maqâshid al-syarî`ah is part of the basic conception air Almighty God with the aim of creating prosperity for the people of Indonesia. In this study, the approach used is the doctrinal bases to study literature. This study is the strengthening of the maqâshid al-syarî`ah as the basis for the development of Islamic law.Abstrak:Kajian ini merupakan bagian dari upaya untuk sistematisasi konsep dasar dari nilai-nilai syari’ah sebagai pondasi dalam kehidupan berbangsa dan kehidupan bernegara, dimana orientasi tersebut adalah untuk mewujudkan hakikat kehidupan dalam beragama melalui maqâshid al-syarî`ah. Islam sebagai al-dîn telah memberikan dasar-dasar kehidupan umat Muslim melalui al-Qur’an dan al-Sunnah. Kedua hal tersebut mengandung nilai-nilai tuntunan kehidupan umat manusia termasuk dalam menjalankan syariah bagi umat Muslim. Syari’ah dalam perspektif terminologi merupakan “jalan”. Sedangkan secara isthilâhî, ia dimaknai sebagai jalan untuk sampai kepada Allah SWT. Makna dasar dari syari’ah itu sendiri harus diwujudkan dalam pemahaman dasar maqâshid al-syarî’ah, di

  15. MENUJU HUKUM ISLAM YANG INKLUSIF-HUMANISTIS: ANALISIS PEMIKIRAN JASSER AUDA TENTANG MAQA╤ĪD AL-SHARĪ’AH

    Directory of Open Access Journals (Sweden)

    Muhammad Salahuddin

    2015-03-01

    Full Text Available Abstract:   Methodological debates in the study of maqā╣īd al-sharī‘ah presented several variants of polarization, as doctrinaire-normative-deductive and historical-empirical-inductive. This paper aims to probe carefully the theory of meaning the maqā╣īd al-sharī‘ah offered by Jasser Auda. It was found that Auda’s offer come from his observation on the failure of Islamic law to reconstruct the values embodied in authoritative texts (Qur’an, Sunnah which are compatible with the social, economical, and political development of modern society. Implementation of maqā╣īd al-shari‘ah must be paralleled with maqā╣īd al-mukallaf, so that Islamic sharī‘ah in its humanist face in accordance with its mission as ra╪mah li al-‘alamīn can be realized.Abstrak:   Perdebatan metodologis dalam kajian tentang maqā╣īd al-sharī‘ah menghadirkan beberapa varian polarisasi, seperti doktriner-normatif-deduktif dan empiris-historis-induktif. Tulisan ini bertujuan untuk menelisik secara cermat teori pemaknaan maqā╣īd al-sharī‘ah yang ditawarkan oleh Jasser Auda. Ditemukan bahwa tawaran itu hadir beranjak dari kegelisahan Auda atas kegagalan hukum Islam dalam merekonstruksi nilai yang terkandung dalam teks otoritatif (Qur’an-Sunnah yang kompatibel dengan perkembangan sosial-ekonomi-politik masyarakat modern. Implementasi maqā╣īd al-shārī‘ah harus diparalelkan dengan maqā╣īd al-mukallaf, sehingga syariah Islam dalam wajah yang humanis yang sejalan dengan misinya sebagai ra╪mah li al-‘ālamīn dapat terwujud.

  16. Cytokine responses in patients with mild or severe influenza A(H1N1)pdm09.

    Science.gov (United States)

    Bradley-Stewart, A; Jolly, L; Adamson, W; Gunson, R; Frew-Gillespie, C; Templeton, K; Aitken, C; Carman, W; Cameron, S; McSharry, C

    2013-09-01

    Influenza virus affects millions of people worldwide each year. More severe infection occurs in the elderly, very young and immunocompromised. In 2009, a new variant of swine origin (influenza A(H1N1)pdm09 virus) emerged that produced severe disease in young healthy adults. The aim of this study was to determine whether cytokine concentrations are associated with clinical outcome in patients infected influenza A(H1N1)pdm09 virus. Plasma concentration of 32 cytokines and growth factors were measured using a multiplex bead immunoassay and conventional ELISA in four patient groups. Patients with severe and mild influenza A(H1N1)pdm09 virus infection, rhinovirus infection and healthy volunteers were investigated. In addition, serial samples of respiratory secretions from five patients with severe influenza A(H1N1)pdm09 virus infection were examined. The majority of cytokines measured were elevated in patients with viral respiratory infections compared to the healthy controls. Concentrations of IL-6, IL-10, IL-15, IP-10, IL-2R, HGF, ST2 and MIG were significantly higher (p<0.05) and EGF significantly lower (p=0.0001) in patients with severe influenza A(H1N1)pdm09 virus infection compared to those with mild influenza A(H1N1)pdm09 virus and rhinovirus infection. A number of cytokines were found to be substantially elevated in patients with severe influenza A(H1N1)pdm09 virus infection. This supports and extends other published work suggesting a role for proinflammatory cytokines in influenza-induced lung pathology. Interestingly, EGF was significantly lower in patients with severe infection suggesting it is actively suppressed. As EGF has a role in role in cell proliferation and tissue repair, it may protect the lung from host or virus mediated damage. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing.

    Science.gov (United States)

    Zeng, Fuxing; Zou, Zhisong; Niu, Liwen; Li, Xu; Teng, Maikun

    2013-08-01

    AhV_aPA, the acidic PLA₂ purified from Agkistrodon halys pallas venom, was previously reported to possess a strong enzymatic activity and can remarkably induce a further contractile response on the 60 mM K⁺-induced contraction with an EC₅₀ in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p-bromo-phenacyl-bromide (pBPB), which can completely inhibit the enzymatic activity of AhV_aPA, did not significantly reduce the contractile response on vessel rings induced by AhV_aPA, indicating that the vasoconstrictor effects of AhV_aPA are independent of the enzymatic activity. The inhibitor experiments showed that the contractile response induced by AhV_aPA is mainly attributed to the Ca²⁺ releasing from Ca²⁺ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca²⁺ release from SR is related to the activation of inositol trisphosphate receptors (IP₃Rs) rather than ryanodine receptors (RyRs). Furthermore, the vasoconstrictor effect could be strongly reduced by pre-incubation with heparin, indicating that the basic amino acid residues on the surface of AhV_aPA may be involved in the interaction between AhV_aPA and the molecular receptors. These findings offer new insights into the functions of snake PLA₂ and provide a novel pathogenesis of A. halys pallas venom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Seroprevalence study in Vojvodina (Serbia following 2009 pandemic influenza A(H1N1v

    Directory of Open Access Journals (Sweden)

    Petrović Vladimir

    2012-01-01

    Full Text Available Introduction. The seroprevalence study was performed in Vojvodina during May and June 2010 in order to asses the effects of the 2009 pandemic influenza A(H1N1v epidemic on herd immunity. It was a part of the Serbian Ministry of Health funded nationwide study. Objective. Prevalence of antibodies against 2009 pandemic influenza A(H1N1v was determined in a 1% sample of the population monitored for influenza-like illness and acute respiratory infections in Vojvodina through sentinel surveillance system. Methods. The study sample involved a total of 1004 inhabitants of Vojvodina. The control group consisted of randomly selected and age-adjusted 1054 sera collected in the pre-pandemic period. Sera were tested by the reaction of hemagglutination inhibition using influenza A/California/7/2009 (H1N1 antigen in dilution from 1:8 to 1:256. Antibody titers ≥1:32 and ≥1:8 were considered protective and diagnostic, respectively. Results. The differences between control and study sera in all age groups were significant for both diagnostic ≥1/8 and protective titres ≥1/32 of hemagglutination inhibition antibodies (chi square test, p<0.001. The highest percentage of seropositive subjects was registered in the age group 15-19 years followed by children aged 5-14 years. Both diagnostic and protective titres were about twice higher in the vaccinated as compared to the non-vaccinated group. There were no statistically significant differences in seroprevalence between seven districts of Vojvodina. Conclusion. The 2009 pandemic influenza A(H1N1v epidemic significantly influenced the herd immunity in our population regardless of low immunization coverage with highest immunity levels in adolescents aged 15-19 years and with similar herd immunity levels in all the regions in the province six months after the outbreak.

  19. Maqasid al-Shari’ah as a Framework for Economic Development Theorization

    Directory of Open Access Journals (Sweden)

    Abdullahi Abubakar LAMIDO

    2016-04-01

    Full Text Available Development studies has so far created a huge intellectual resource, including theories, models and policy prescriptions that have been implemented in most developing economies. However, development theorization has been generally dominated by the western materialist paradigm which is antithetical to the very philosophical foundations of Islam. Muslims, constituting at least a quarter of the world population, mostly live in the less developed economies and are therefore among the largest consumers of these materialist theories.  Based on the premises that the Muslim world cannot address its multifarious development challenges by relying only on imported theories and models, and that as important stakeholders in the world, Muslims need to contribute to the global development discourse; this paper presents an Islamic alternative approach to the analysis of development based on the theory of maqasid al-Shari’ah. The paper proposes a maqasid-based development approach which sees development from the perspective of drawing benefit and removing harm, which require promoting things that make life easy, meaningful and prosperous and blocking all means to harm, socio-economic difficulty and underdevelopment. The three-stages development approach focuses on promoting wellbeing through the preservation and enhancement of five essential components; faith, life, intellect, offspring and wealth. The paper submits that maqasid al-Shari’ah is a veritable framework for, inter alia, formulating development policies and prioritizing development projects. The strength of the approach lies in the proper place it accords to faith, spirituality, and moral ethics as trigger mechanisms for sustained moderate development in addition to its emphasis on all-encompassing but moderate material progress. The paper calls for an extensive study of the science of maqasid al-Shari’ah as it pertains to economic development discourse.  

  20. Post space preparation timing of root canals sealed with AH Plus sealer

    Science.gov (United States)

    Kim, Hae-Ri; Kim, Young Kyung

    2017-01-01

    Objectives To determine the optimal timing for post space preparation of root canals sealed with epoxy resin-based AH Plus sealer in terms of its polymerization and influence on apical leakage. Materials and Methods The epoxy polymerization of AH Plus (Dentsply DeTrey) as a function of time after mixing (8, 24, and 72 hours, and 1 week) was evaluated using Fourier transform infrared (FTIR) spectroscopy and microhardness measurements. The change in the glass transition temperature (Tg) of the material with time was also investigated using differential scanning calorimetry (DSC). Fifty extracted human single-rooted premolars were filled with gutta-percha and AH Plus, and randomly separated into five groups (n = 10) based on post space preparation timing (immediately after root canal obturation and 8, 24, and 72 hours, and 1 week after root canal obturation). The extent of apical leakage (mm) of the five groups was compared using a dye leakage test. Each dataset was statistically analyzed by one-way analysis of variance and Tukey's post hoc test (α = 0.05). Results Continuous epoxy polymerization of the material with time was observed. Although the Tg values of the material gradually increased with time, the specimens presented no clear Tg value at 1 week after mixing. When the post space was prepared 1 week after root canal obturation, the leakage was significantly higher than in the other groups (p < 0.05), among which there was no significant difference in leakage. Conclusions Poor apical seal was detected when post space preparation was delayed until 1 week after root canal obturation. PMID:28194361

  1. Photometric solution and period analysis of the contact binary system AH Cnc

    Science.gov (United States)

    Peng, Ying-Jiang; Luo, Zhi-Quan; Zhang, Xiao-Bin; Deng, Li-Cai; Wang, Kun; Tian, Jian-Feng; Yan, Zheng-Zhou; Pan, Yang; Fang, Wei-Jing; Feng, Zhong-Wen; Tang, De-Lin; Liu, Qi-Li; Sun, Jin-Jiang; Zhou, Qiang

    2016-10-01

    Photometric observations of AH Cnc, a W UMa-type system in the open cluster M67, were carried out by using the 50BiN telescope. About 100 h of time-series B- and V -band data were taken, based on which eight new times of light minima were determined. By applying the Wilson-Devinney method, the light curves were modeled and a revised photometric solution of the binary system was derived. We confirmed that AH Cnc is a deep contact (f = 51%), low mass-ratio (q = 0.156) system. Adopting the distance modulus derived from study of the host cluster, we have re-calculated the physical parameters of the binary system, namely the masses and radii. The masses and radii of the two components were estimated to be respectively 1.188(±0.061) M ⊙, 1.332(±0.063) R ⊙ for the primary component and 0.185(±0.032) M ⊙, 0.592(±0.051) R ⊙ for the secondary. By adding the newly derived minimum timings to all the available data, the period variations of AH Cnc were studied. This shows that the orbital period of the binary is continuously increasing at a rate of dp/dt = 4.29 × 10‑10 d yr‑1. In addition to the long-term period increase, a cyclic variation with a period of 35.26 yr was determined, which could be attributed to an unresolved tertiary component of the system.

  2. Narcolepsy and influenza A(H1N1) pandemic 2009 vaccination in the United States.

    Science.gov (United States)

    Duffy, Jonathan; Weintraub, Eric; Vellozzi, Claudia; DeStefano, Frank

    2014-11-11

    To assess the occurrence of narcolepsy after influenza vaccines used in the United States that contained the influenza A(H1N1)pdm09 virus strain. A population-based cohort study in the Vaccine Safety Datalink with an annual population of more than 8.5 million people. All persons younger than 30 years who received a 2009 pandemic or a 2010-2011 seasonal influenza vaccine were identified. Their medical visit history was searched for a first-ever occurrence of an ICD-9 narcolepsy diagnosis code through the end of 2011. Chart review was done to confirm the diagnosis and determine the date of symptom onset. Cases were patients who met the International Classification of Sleep Disorders, 2nd edition, narcolepsy diagnostic criteria. We compared the observed number of cases after vaccination to the number expected to occur by chance alone. The number vaccinated with 2009 pandemic vaccine was 650,995 and with 2010-2011 seasonal vaccine was 870,530. Among these patients, 70 had a first-ever narcolepsy diagnosis code after vaccination, of which 16 had a chart-confirmed incident diagnosis of narcolepsy. None had their symptom onset during the 180 days after receipt of a 2009 pandemic vaccine compared with 6.52 expected, and 2 had onset after a 2010-2011 seasonal vaccine compared with 8.83 expected. Influenza vaccines containing the A(H1N1)pdm09 virus strain used in the United States were not associated with an increased risk of narcolepsy. Vaccination with the influenza A(H1N1)pdm09 vaccine viral antigens does not appear to be sufficient by itself to increase the incidence of narcolepsy in a population. © 2014 American Academy of Neurology.

  3. An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

    Science.gov (United States)

    Aguilar-Yáñez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio A.; López-Pacheco, Felipe; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Lara-Mayorga, Itzel M.; Webb-Vargas, Yenny; León-Angel, Felipe O.; Rivero-Aranda, Ramón E.; Oropeza-Almazán, Yuriana; Ruiz-Palacios, Guillermo M.; Zertuche-Guerra, Manuel I.; DuBois, Rebecca M.; White, Stephen W.; Schultz-Cherry, Stacey; Russell, Charles J.; Alvarez, Mario M.

    2010-01-01

    Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings We expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. PMID:20661476

  4. An influenza A/H1N1/2009 hemagglutinin vaccine produced in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    José M Aguilar-Yáñez

    Full Text Available BACKGROUND: The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. METHODOLOGY/PRINCIPAL FINDINGS: We expressed the globular HA receptor binding domain, referred to here as HA(63-286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA(63-286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. CONCLUSIONS/SIGNIFICANCE: Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy.

  5. POPULATION IMMUNITY TO INFLUENZA VIRUS A(H1N1pdm09, A(H3N2 AND B IN THE ADULT POPULATION OF THE RUSSIAN FEDERATION LONG-TERM RESEARCH RESULTS

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    O. S. Konshina

    2017-01-01

    Full Text Available Analysis of changes in the population immunity level in adults for more than 20 Russian cities, collaborating with the Federal Center for Influenza, to circulating influenza viruses A(H1N1pdm09, A(H3N2 and B in the period from 2009 to 2015 performed. By the beginning of the pandemic (October 2009 the population of Russia was almost seronegative to influenza A(H1N1pdm09 virus. After the pandemia first wave mean geometric titers (GMTs of antibodies to the pandemic virus increased by 2.6 times, after the second one by 4.9 times in comparison with initial GMT (1:5.5. A consistent increase in GMTs antibody after each of the subsequent seasons of active circulation of pandemic virus was observed reaching the maximum (1:41 by April 2013, after the next epidemic caused by this virus. The proportion of people with protective antibody titers in October 2009 to already started circulating influenza A(H1N1pdm09 virus was 8.2%, to influenza A(H3N2 virus — 58.3%, and influenza B virus — 59.7%. Level of population immunity in adults to seasonal influenza A(H3N2 and B viruses throughout the observed period was significantly higher than to influenza virus A(H1N1pdm09. The percentage of persons with protective antibody titers during the observed period varied for virus A(H3N2 in the range from 58.3 to 75.5%, for influenza B virus — from 59.7 to 82.3%. Accordingly, incidence rate for ILI and ARI in adult groups the population during influenza epidemic caused by these pathogens was lower than in the epidemics, associated with active circulation of influenza A(H1N1pdm09 virus. The data obtained can be used in influenza forecasting for the upcoming season regarding the etiology and the expected epidemic intensity need for the relevant preventing measures development to decrease the burden from influenza.

  6. Population-level antibody estimates to novel influenza A/H7N9.

    Science.gov (United States)

    Boni, Maciej F; Chau, Nguyen Van Vinh; Dong, Nguyen; Todd, Stacy; Nhat, Nguyen Thi Duy; de Bruin, Erwin; van Beek, Janko; Hien, Nguyen Tran; Simmons, Cameron P; Farrar, Jeremy; Koopmans, Marion

    2013-08-15

    There are no contemporary data available describing human immunity to novel influenza A/H7N9. Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to 5 avian influenza virus antigens, using a protein microarray. General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5 and lower than titers against H9. The highest titers were observed for human influenza virus subtypes. Titers to avian influenza virus antigens increased with age and with geometric mean antibody titer to human influenza virus antigens. There were no titer differences between the urban and the rural location in our study.

  7. Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.

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    Stefano Merler

    Full Text Available BACKGROUND: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated. METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40, was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model. RESULTS: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%. Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in

  8. Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin

    OpenAIRE

    Lin, Yi Pu; Xiong, Xiaoli; Wharton, Stephen A.; Martin, Stephen R.; Coombs, Peter J.; Vachieri, Sebastien G.; Christodoulou, Evangelos; Walker, Philip A.; Liu, Junfeng; John J Skehel; Gamblin, Steven J.; Hay, Alan J.; Daniels, Rodney S; McCauley, John W.

    2012-01-01

    The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). By 2001, the avidity of human H3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. These changes in ...

  9. Performance features of 22-cell, 19Ah single pressure vessel nickel hydrogen battery

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    1996-01-01

    Two 22-cells 19Ah Nickel-Hydrogen (Ni-H2) Single Pressure Vessel (SPV) Qual batteries, one each from EPI/Joplin and EPI/Butler, were designed and procured. The two batteries differ in the cell encapsulation technology, stack preload, and activation procedure. Both the Butler and Joplin batteries met the specified requirements when subjected to qualification testing and completed 2100 and 1300 LEO cycles respectively, with nominal performance. This paper discusses advantages, design features, testing procedures, and results of the two single pressure vessel Ni-H2 batteries.

  10. A Highly Immunogenic Vaccine against A(H7N9) Influenza Virus

    Science.gov (United States)

    Cao, Weiping; Liepkalns, Justine; Hassan, Ahmed O.; Kamal, Ram; Hofstetter, Amelia R.; Amoah, Samuel; Kim, Jin Hyang; Reber, Adrian; Stevens, James; Katz, Jacqueline M.; Gangappa, Shivaprakash; York, Ian; Mittal, Suresh K.; Sambhara, Suryaprakash

    2016-01-01

    Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/(H7N9) viral challenge suggesting its potential utility as a pandemic vaccine. PMID:26765287

  11. Investigation of difficult component effects on FEM vibration prediction for the AH-1G helicopter

    Science.gov (United States)

    Dompka, Robert V.

    1988-01-01

    Under the NASA-sponsored Design Analysis Methods for Vibrations program, a series of ground vibration tests and NASTRAN finite element model correlations were conducted on the Bell AH-1G helicopter gunship to investigate the effects of difficult components on the vibration response of the airframe. Secondary structure and damping were found to have significant effects on the frequency response of the airframe above 15 Hz. The nonlinear effects of thrust stiffening and elastomeric mounts on the low-frequency pylon modes below the main rotor were also significant.

  12. The application of Shari’ah and international human rights law in Saudi Arabia

    OpenAIRE

    Al-Rodiman, Abdulaziz

    2013-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel University The present dissertation provides an analytical and comparative study of the application of Islamic law (Shari’ah) and international human rights law in the Kingdom of Saudi Arabia. It provides an analysis of the sources of Islamic law as well as the sources of international law to set the background for analysis and defines the nature of both laws. It also tackles the subject of the domes...

  13. Performance features of 22-cell, 19Ah single pressure vessel nickel hydrogen battery

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    1996-01-01

    Two 22-cells 19Ah Nickel-Hydrogen (Ni-H2) Single Pressure Vessel (SPV) Qual batteries, one each from EPI/Joplin and EPI/Butler, were designed and procured. The two batteries differ in the cell encapsulation technology, stack preload, and activation procedure. Both the Butler and Joplin batteries met the specified requirements when subjected to qualification testing and completed 2100 and 1300 LEO cycles respectively, with nominal performance. This paper discusses advantages, design features, testing procedures, and results of the two single pressure vessel Ni-H2 batteries.

  14. Takaful (Islamic Insurance), Risk Management and Maqasid Al- Sharī‘Ah 

    OpenAIRE

    Sabirzyanov, Ruslan; Hashim, Mohamad Haidir

    2015-01-01

    Risk presents in the life of a human being from beginning of his/her life until the end. Daily transactions, financial operations are not exceptions from subjects of a risk. Moreover, risk does not differentiate between Islamic and non-Islamic financial transactions. However, the question boils down is “what is view of Islam to a risk and should it be managed and how?” This paper attempts to analyse and examine risk management in takaful from a standpoint of Sharī‘ah objectives. The study is ...

  15. An outbreak of influenza A/H3N2 in a Zambian school dormitory.

    Science.gov (United States)

    Mizuta, K; Oshitani, H; Mpabalwani, E M; Kasolo, F C; Luo, N P; Suzuki, H; Numazaki, Y

    1995-03-01

    There was an outbreak of "a mysterious disease" at a Zambian school dormitory in September, 1993. Investigation with questionnaire and collection of throat swab specimens for virus isolation were carried out on 46 patients to identify the causative agent. In this outbreak, most of the patients showed similar symptoms such as fever, headache, sore throat, cough, etc. The disease had spread to all dormitories within a couple of days after the onset of the first cases. From these patients, 13 influenza viruses A/H3N2 were isolated on MDCK cell line. This was a first ever confirmed outbreak of influenza virus infection in Zambia.

  16. MiRNA-548ah, a Potential Molecule Associated with Transition from Immune Tolerance to Immune Activation of Chronic Hepatitis B

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    Tong-Jing Xing

    2014-08-01

    Full Text Available Objective: The present study aims to identify the differently expressed microRNA (miRNA molecules and target genes of miRNA in the immune tolerance (IT and immune activation (IA stages of chronic hepatitis B (CHB. Methods: miRNA expression profiles of peripheral blood mononuclear cells (PBMCs at the IT and IA stages of CHB were screened using miRNA microarrays and authenticated using a quantitative real-time polymerase chain reaction (RT-PCR. Gene ontology (GO and the Kyoto encyclopedia of genes and genomes (KEGG were used to analyze the significant functions and pathways of possible target genes of miRNAs. Assays of the gain and loss of function of the miRNAs were performed to verify the target genes in THP-1 cell lines. The luciferase reporter test was used on 293T cells as direct targets. Results: Significantly upregulated miR-548 and miR-4804 were observed in the miRNA microarrays and confirmed by RT-PCR in PBMCs at the IT and IA stages of CHB. GO and KEGG analysis revealed that MiR-548 and miR-4804 could be involved in numerous signaling pathways and protein binding activity. IFNγR1 was predicted as a target gene and validated as the direct gene of MiR-548. Significant negative correlation was found between the miR-548ah and mRNA levels of IFN-γR1 in CHB patients. Conclusions: The abnormal expression profiles of miRNA in PBMCs could be closely associated with immune activation of chronic HBV infection. miR-548, by targeting IFN-γR1, may represent a mechanism that can facilitate viral pathogenesis and help determine new therapeutic molecular targets.

  17. Loss of androgen receptor-dependent growth suppression by prostate cancer cells can occur independently from acquiring oncogenic addiction to androgen receptor signaling.

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    Jason M D'Antonio

    Full Text Available The conversion of androgen receptor (AR signaling as a mechanism of growth suppression of normal prostate epithelial cells to that of growth stimulation in prostate cancer cells is often associated with AR mutation, amplification and over-expression. Thus, down-regulation of AR signaling is commonly therapeutic for prostate cancer. The E006AA cell line was established from a hormone naïve, localized prostate cancer. E006AA cells are genetically aneuploid and grow equally well when xenografted into either intact or castrated male NOG but not nude mice. These cells exhibit: 1 X chromosome duplication and AR gene amplification, although paradoxically not coupled with increased AR expression, and 2 somatic, dominant-negative Serine-599-Glycine loss-of-function mutation within the dimerization surface of the DNA binding domain of the AR gene. No effect on the growth of E006AA cells is observed using targeted knockdown of endogenous mutant AR, ectopic expression of wild-type AR, or treatment with androgens or anti-androgens. E006AA cells represent a prototype for a newly identified subtype of prostate cancer cells that exhibit a dominant-negative AR loss-of-function in a hormonally naïve patient. Such loss-of-function eliminates AR-mediated growth suppression normally induced by normal physiological levels of androgens, thus producing a selective growth advantage for these malignant cells in hormonally naïve patients. These data highlight that loss of AR-mediated growth suppression is an independent process, and that, without additional changes, is insufficient for acquiring oncogene addiction to AR signaling. Thus, patients with prostate cancer cells harboring such AR loss-of-function mutations will not benefit from aggressive hormone or anti-AR therapies even though they express AR protein.

  18. Impact of Influenza A(H1N1)pdm09 Virus on Circulation Dynamics of Seasonal Influenza Strains in Kenya

    Science.gov (United States)

    Majanja, Janet; Njoroge, Rose N.; Achilla, Rachel; Wurapa, Eyako K.; Wadegu, Meshack; Mukunzi, Silvanos; Mwangi, Josephat; Njiri, James; Gachara, George; Bulimo, Wallace

    2013-01-01

    We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008–July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription–polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya. PMID:23458953

  19. Reconstruction of the Evolutionary Dynamics of the A(H1N1)pdm09 Influenza Virus in Italy during the Pandemic and Post-Pandemic Phases

    Science.gov (United States)

    Zehender, Gianguglielmo; Lai, Alessia; Gabanelli, Elena; Ranghiero, Alberto; Ebranati, Erika; Amendola, Antonella; Campanini, Giulia; Rovida, Francesca; Ciccozzi, Massimo; Galli, Massimo; Baldanti, Fausto; Zanetti, Alessandro Remo

    2012-01-01

    The aim of this study was to reconstruct the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Italy during two epidemic seasons (2009/2010 and 2010/2011) in the light of the forces driving the evolution of the virus. Nearly six thousands respiratory specimens were collected from patients with influenza-like illness within the framework of the Italian Influenza Surveillance Network, and the A(H1N1)pdm09 hemagglutinin (HA) gene was amplified and directly sequenced from 227 of these. Phylodynamic and phylogeographical analyses were made using a Bayesian Markov Chain Monte Carlo method, and codon-specific positive selection acting on the HA coding sequence was evaluated. The global and local phylogenetic analyses showed that all of the Italian sequences sampled in the post-pandemic (2010/2011) season grouped into at least four highly significant Italian clades, whereas those of the pandemic season (2009/2010) were interspersed with isolates from other countries at the tree root. The time of the most recent common ancestor of the strains circulating in the pandemic season in Italy was estimated to be between the spring and summer of 2009, whereas the Italian clades of the post-pandemic season originated in the spring of 2010 and showed radiation in the summer/autumn of the same year; this was confirmed by a Bayesian skyline plot showing the biphasic growth of the effective number of infections. The local phylogeography analysis showed that the first season of infection originated in Northern Italian localities with high density populations, whereas the second involved less densely populated localities, in line with a gravity-like model of geographical dispersion. Two HA sites, codons 97 and 222, were under positive selection. In conclusion, the A(H1N1)pdm09 virus was introduced into Italy in the spring of 2009 by means of multiple importations. This was followed by repeated founder effects in the post-pandemic period that originated specific Italian clades

  20. Modelling influenza A(H1N1) 2009 epidemics using a random network in a distributed computing environment.

    Science.gov (United States)

    González-Parra, Gilberto; Villanueva, Rafael-J; Ruiz-Baragaño, Javier; Moraño, Jose-A

    2015-03-01

    In this paper we propose the use of a random network model for simulating and understanding the epidemics of influenza A(H1N1). The proposed model is used to simulate the transmission process of influenza A(H1N1) in a community region of Venezuela using distributed computing in order to accomplish many realizations of the underlying random process. These large scale epidemic simulations have recently become an important application of high-performance computing. The network model proposed performs better than the traditional epidemic model based on ordinary differential equations since it adjusts better to the irregularity of the real world data. In addition, the network model allows the consideration of many possibilities regarding the spread of influenza at the population level. The results presented here show how well the SEIR model fits the data for the AH1N1 time series despite the irregularity of the data and returns parameter values that are in good agreement with the medical data regarding AH1N1 influenza virus. This versatile network model approach may be applied to the simulation of the transmission dynamics of several epidemics in human networks. In addition, the simulation can provide useful information for the understanding, prediction and control of the transmission of influenza A(H1N1) epidemics.

  1. FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs.

    Science.gov (United States)

    Kemble, David J; McCullough, Laura L; Whitby, Frank G; Formosa, Tim; Hill, Christopher P

    2015-10-15

    FACT, a heterodimer of Spt16 and Pob3, is an essential histone chaperone. We show that the H2A-H2B binding activity that is central to FACT function resides in short acidic regions near the C termini of each subunit. Mutations throughout these regions affect binding and cause correlated phenotypes that range from mild to lethal, with the largest individual contributions unexpectedly coming from an aromatic residue and a nearby carboxylate residue within each domain. Spt16 and Pob3 bind overlapping sites on H2A-H2B, and Spt16-Pob3 heterodimers simultaneously bind two H2A-H2B dimers, the same stoichiometry as the components of a nucleosome. An Spt16:H2A-H2B crystal structure explains the biochemical and genetic data, provides a model for Pob3 binding, and implies a mechanism for FACT reorganization that we confirm biochemically. Moreover, unexpected similarity to binding of ANP32E and Swr1 with H2A.Z-H2B reveals that diverse H2A-H2B chaperones use common mechanisms of histone binding and regulating nucleosome functions.

  2. The Concept of Social Responsibility Disclosures for Islamic Banks based on Shari'ah Enterprose Theory

    Directory of Open Access Journals (Sweden)

    Intan Meutia

    2010-12-01

    Full Text Available This research aims to develop the concept and characteristics of social responsibility disclosure and items for the social responsibility disclosure of Islamic banks. This research was conducted based on the critical paradigm by using Habermas’s Theory of Communication Action extended to spirituality in understanding social reality. This study also uses Shari’ah Enterprise Theory to analyze and to produce the concept of social responsibility disclosure for Islamic banks. Analysis was conducted on the annual reports of three Islamic banks in Indonesia, Bank Mega Syariah, Bank Syariah Mandiri and Bank Muamalat Indonesia. Interviews with stakeholders, including direct and indirect stakeholders were also conducted. Spiritual values were found during the research. These values are sharing, rahmatan lil alamin and maslaha. These values are used as guidance in developing items of social responsibility disclosure. Furthermore, a concept of social responsibility disclosure is derived based on the Shari’ah Enterprise Theory. This research proposes a form of social responsibility disclosure for Islamic banks that show efforts to meet vertical accountability to God, and horizontal accountability to people and environment, as well as to consider the material and spiritual needs of stakeholders and to disclose information both qualitatively and quantitatively.

  3. The pandemic potential of avian influenza A(H7N9) virus: a review.

    Science.gov (United States)

    Tanner, W D; Toth, D J A; Gundlapalli, A V

    2015-12-01

    In March 2013 the first cases of human avian influenza A(H7N9) were reported to the World Health Organization. Since that time, over 650 cases have been reported. Infections are associated with considerable morbidity and mortality, particularly within certain demographic groups. This rapid increase in cases over a brief time period is alarming and has raised concerns about the pandemic potential of the H7N9 virus. Three major factors influence the pandemic potential of an influenza virus: (1) its ability to cause human disease, (2) the immunity of the population to the virus, and (3) the transmission potential of the virus. This paper reviews what is currently known about each of these factors with respect to avian influenza A(H7N9). Currently, sustained human-to-human transmission of H7N9 has not been reported; however, population immunity to the virus is considered very low, and the virus has significant ability to cause human disease. Several statistical and geographical modelling studies have estimated and predicted the spread of the H7N9 virus in humans and avian species, and some have identified potential risk factors associated with disease transmission. Additionally, assessment tools have been developed to evaluate the pandemic potential of H7N9 and other influenza viruses. These tools could also hypothetically be used to monitor changes in the pandemic potential of a particular virus over time.

  4. Metapopulation dynamics enable persistence of influenza A, including A/H5N1, in poultry.

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    Parviez Rana Hosseini

    Full Text Available Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified.

  5. The Linear Span of Projections in AH Algebras and for Inclusions of C*-Algebras

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    Dinh Trung Hoa

    2013-01-01

    Full Text Available In the first part of this paper, we show that an AH algebra A=lim→(Ai,ϕi has the LP property if and only if every element of the centre of Ai belongs to the closure of the linear span of projections in A. As a consequence, a diagonal AH-algebra has the LP property if it has small eigenvalue variation in the sense of Bratteli and Elliott. The second contribution of this paper is that for an inclusion of unital C*-algebras P⊂A with a finite Watatani index, if a faithful conditional expectation E:A→P has the Rokhlin property in the sense of Kodaka et al., then P has the LP property under the condition thatA has the LP property. As an application, let A be a simple unital C*-algebra with the LP property, α an action of a finite group G onto Aut(A. If α has the Rokhlin property in the sense of Izumi, then the fixed point algebra AG and the crossed product algebra A ⋊α G have the LP property. We also point out that there is a symmetry on the CAR algebra such that its fixed point algebra does not have the LP property.

  6. Functions of Danggui Buxue Tang, a Chinese Herbal Decoction Containing Astragali Radix and Angelicae Sinensis Radix, in Uterus and Liver are Both Estrogen Receptor-Dependent and -Independent

    Directory of Open Access Journals (Sweden)

    Oliver Zierau

    2014-01-01

    Full Text Available Danggui Buxue Tang (DBT, a herbal decoction containing Astragali Radix (AR and Angelicae Sinensis Radix (ASR, has been used in treating menopausal irregularity in women for more than 800 years in China. Pharmacological results showed that DBT exhibited significant estrogenic properties in vitro, which therefore suggested that DBT could activate the nuclear estrogen receptors. Here, we assessed the estrogenic properties of DBT in an ovariectomized in vivo rat model: DBT was applied to the ovariectomized rats for 3 days. The application of DBT did not alter the weight of uterus and liver, as well as the transcript expression of the proliferation markers including the estrogen receptors α and β. However, DBT stimulated the transcript expression of the estrogen responsive genes. In addition, the inductive role of DBT on the expression of members of the aryl hydrocarbon receptor family in uterus and liver of ovariectomized rats was confirmed. These responses of DBT however were clearly distinct from the response pattern detectable here for 17β-estradiol. Therefore, DBT exhibited weak, but significant, estrogenic properties in vivo; however, some of its activities were independent of the estrogen receptor. Thus, DBT could be an exciting Chinese herbal decoction for an alternative treatment of hormone replacement therapy for women in menopause without subsequent estrogenic side effects.

  7. Farnesoid X receptor-dependent and -independent pathways mediate the transcriptional control of human fibroblast growth factor 19 by vitamin A.

    Science.gov (United States)

    Jahn, Daniel; Sutor, Dominic; Dorbath, Donata; Weiß, Johannes; Götze, Oliver; Schmitt, Johannes; Hermanns, Heike M; Geier, Andreas

    2016-02-01

    Fibroblast growth factor 19 (FGF19) is a gut-derived hormone that controls bile acid (BA), carbohydrate and lipid metabolism. Whereas strong evidence supports a key role of BAs and farnesoid X receptor (FXR) for the control of FGF19 expression, information on other regulators is limited. In mice, FGF15 expression (ortholog of human FGF19) is induced by vitamin A (VitA) in an FXR-dependent manner. However, the significance of this finding for human FGF19 is currently unclear. Here, we demonstrate that VitA derivatives induce FGF19 in human intestinal cell lines by a direct transcriptional mechanism. In contrast to mouse FGF15, however, this direct regulation is not dependent on FXR but mediated by retinoic acid receptors (RARs) and their interaction with a novel DR-5 element in the human FGF19 gene. In addition to this direct effect, VitA derivatives impacted on the BA-mediated control of FGF19 by regulation of FXR protein levels. In conclusion, VitA regulates human FGF19 expression through FXR-dependent and -independent pathways. Moreover, we suggest that considerable mechanistic differences exist between humans and mice with regard to the nuclear receptors controlling the VitA-FGF15/19 axis. These findings may implicate a clinical relevance of RAR-activating VitA derivatives for the regulation of FGF19 levels in humans.

  8. Highly pathogenic avian influenza A(H5N1) mutants transmissible by air are susceptible to human and animal neutralizing antibodies.

    Science.gov (United States)

    Du, Lanying; Li, Ye; Zhao, Guangyu; Wang, Lili; Zou, Peng; Lu, Lu; Zhou, Yusen; Jiang, Shibo

    2013-10-15

    A laboratory-generated reassortant H5 hemagglutinin (HA)/influenza A(H1N1) strain containing 4 mutations in influenza A(H5N1) HA has become transmissible by air among mammals. Here, we constructed 15 influenza A(H5N1) pseudoviruses containing a single mutation or a combination of mutations and showed that the pseudoviruses were susceptible to neutralizing antibodies from patients with influenza A(H5N1) infection and from mice immunized with a vaccine containing the conserved HA1 sequence of influenza A(H5N1). These results indicate that antibodies in patients currently infected by influenza A(H5N1) and antibodies induced by vaccines containing conserved sequences in HA1 of wild-type influenza A(H5N1) are highly effective in cross-neutralizing future influenza A(H5N1) mutants with airborne transmissibility, suggesting that human influenza pandemics caused by these influenza A(H5N1) variants can be prevented.

  9. Predominance of HA-222D/G polymorphism in influenza A(H1N1pdm09 viruses associated with fatal and severe outcomes recently circulating in Germany.

    Directory of Open Access Journals (Sweden)

    Marianne Wedde

    Full Text Available Influenza A(H1N1pdm09 viruses cause sporadically very severe disease including fatal clinical outcomes associated with pneumonia, viremia and myocarditis. A mutation characterized by the substitution of aspartic acid (wild-type to glycine at position 222 within the haemagglutinin gene (HA-D222G was recorded during the 2009 H1N1 pandemic in Germany and other countries with significant frequency in fatal and severe cases. Additionally, A(H1N1pdm09 viruses exhibiting the polymorphism HA-222D/G/N were detected both in the respiratory tract and in blood. Specimens from mild, fatal and severe cases were collected to study the heterogeneity of HA-222 in A(H1N1pdm09 viruses circulating in Germany between 2009 and 2011. In order to enable rapid and large scale analysis we designed a pyrosequencing (PSQ assay. In 2009/2010, the 222D wild-type of A(H1N1pdm09 viruses predominated in fatal and severe outcomes. Moreover, co-circulating virus mutants exhibiting a D222G or D222E substitution (8/6% as well as HA-222 quasispecies were identified (10%. Both the 222D/G and the 222D/G/N/V/Y polymorphisms were confirmed by TA cloning. PSQ analyses of viruses associated with mild outcomes revealed mainly the wild-type 222D and no D222G change in both seasons. However, an increase of variants with 222D/G polymorphism (60% was characteristic for A(H1N1pdm09 viruses causing fatal and severe cases in the season 2010/2011. Pure 222G viruses were not observed. Our results support the hypothesis that the D222G change may result from adaptation of viral receptor specificity to the lower respiratory tract. This could explain why transmission of the 222G variant is less frequent among humans. Thus, amino acid changes at HA position 222 may be the result of viral intra-host evolution leading to the generation of variants with an altered viral tropism.

  10. Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization.

    Science.gov (United States)

    Gualtieri, Maurizio; Ovrevik, Johan; Mollerup, Steen; Asare, Nana; Longhin, Eleonora; Dahlman, Hans-Jørgen; Camatini, Marina; Holme, Jørn A

    2011-08-01

    Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in "classical" apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage.

  11. The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

    LENUS (Irish Health Repository)

    Valenciano, Marta

    2015-06-04

    In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.

  12. Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats.

    Science.gov (United States)

    Hamson, D K; Wainwright, S R; Taylor, J R; Jones, B A; Watson, N V; Galea, L A M

    2013-09-01

    Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.

  13. The calcium-sensing receptor-dependent regulation of cell-cell adhesion and keratinocyte differentiation requires Rho and filamin A.

    Science.gov (United States)

    Tu, Chia-Ling; Chang, Wenhan; Bikle, Daniel D

    2011-05-01

    Extracellular Ca(2+) (Ca(2+)(o)) functioning through the calcium-sensing receptor (CaR) induces E-cadherin-mediated cell-cell adhesion and cellular signals mediating cell differentiation in epidermal keratinocytes. Previous studies indicate that CaR regulates cell-cell adhesion through Fyn/Src tyrosine kinases. In this study, we investigate whether Rho GTPase is a part of the CaR-mediated signaling cascade regulating cell adhesion and differentiation. Suppressing endogenous Rho A expression by small interfering RNA (siRNA)-mediated gene silencing blocked the Ca(2+)(o)-induced association of Fyn with E-cadherin and suppressed the Ca(2+)(o)-induced tyrosine phosphorylation of β-, γ-, and p120-catenin and formation of intercellular adherens junctions. Rho A silencing also decreased the Ca(2+)(o)-stimulated expression of terminal differentiation markers. Elevating the Ca(2+)(o) level induced interactions among CaR, Rho A, E-cadherin, and the scaffolding protein filamin A at the cell membrane. Inactivation of CaR expression by adenoviral expression of a CaR antisense complementary DNA inhibited Ca(2+)(o)-induced activation of endogenous Rho. Ca(2+)(o) activation of Rho required a direct interaction between CaR and filamin A. Interference of CaR-filamin interaction inhibited Ca(2+)(o)-induced Rho activation and the formation of cell-cell junctions. These results indicate that Rho is a downstream mediator of CaR in the regulation of Ca(2+)(o)-induced E-cadherin-mediated cell-cell adhesion and keratinocyte differentiation.

  14. Habituation without NMDA receptor-dependent desensitization of Hering-Breuer apnea reflex in a Mecp2+/- mutant mouse model of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Gang eSong

    2011-05-01

    Full Text Available Nonassociative learning is a basic neuroadaptive behavior exhibited in almost all animal species and sensory modalities but its functions and mechanisms in the mammalian brain are poorly understood. Previous studies have identified two distinct forms of nonassociative learning in the classic Hering-Breuer inflation reflex (HBIR induced apnea in rats: NMDA receptor (NMDAR-independent habituation in a primary vagal pathway and NMDAR-dependent desensitization in a secondary pontine pathway. Here, we show that abnormal nonassociative learning of the HBIR may underlie the endophenotypic tachypnea in an animal model of Rett syndrome (RTT, an autism-spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2. Mecp2+/- symptomatic mice on a mixed-strain background demonstrated significantly increased resting respiratory frequency with shortened expiration and normal inspiratory duration compared with asymptomatic mutants and wild-type controls, a phenotype that is characteristic of girls with RTT. Low-intensity electrical stimulation of the vagus nerve elicited fictive HBIR with time-dependent habituation in both Mecp2+/- and wild-type mice. However, time-dependent desensitization of the HBIR was evidenced only in wild-type controls and asymptomatic mutant mice but was absent or suppressed in Mecp2+/- symptomatic mice or in wild-type mice after blockade of NMDAR with dizocilpine. Remarkably, ~50% of the Mecp2+/- mice developed these X-linked phenotypes despite somatic mosaicism. Such RTT-like respiratory endophenotypes in mixed-strain Mecp2+/- mice differed from those previously reported in Mecp2-/y mice on pure C57BL/6J background. These findings provide the first evidence indicating that impaired NMDAR-dependent desensitization of the HBIR may contribute to the endophenotypic tachypnea in RTT.

  15. Proposed Approach for Best Practices of Shari’ah Corporate Governance in the Malaysian Islamic Capital Market

    Directory of Open Access Journals (Sweden)

    Nawal Kasim

    2014-11-01

    Full Text Available With the rapid growth of Islamic finance industry, the countries offering Islamic products should be preparing standards and guidelines to cater for current market needs to ensure that the industry is operating in a conducive environment. Since Malaysia strives to position itself as a hub for Islamic finance, it must ensure that it proactively works towards moulding the industry. With the needs of the industry, the Central Bank of Malaysia has issued the Shari’ah Governance Framework for Islamic banks and Takaful. This was necessary in view of the lack of guidelines best practices in Shari’ah corporate governance in the Malaysian Islamic capital market. To this end, this study seeks to determine the approach best suited to establish a framework of Shari’ah corporate governance for listed companies in Malaysia. The interview results show that the hybrid approach is best suited to provide the general guidelines as a reference while accommodating the flexibility of Islamic law.

  16. Knowledge and attitudes in regard to pandemic influenza A(H1N1) in a multiethnic community of Malaysia.

    Science.gov (United States)

    Wong, Li Ping; Sam, I-Ching

    2011-06-01

    Assessment of general public's knowledge and attitudes toward the development and prevention of new disease outbreaks is imperative because they have profound effects on health behaviors and may contribute to the control of the epidemic. To investigate the level of knowledge and attitudes towards the influenza A(H1N1) outbreak across various ethnic groups and socio-demographic backgrounds in Malaysia. A cross-sectional, population-based, computer-assisted telephone interview exploring knowledge and attitudes regarding influenza A(H1N1) was conducted in Malaysia. Between July 11 and September 12, 2009, a total of 1,050 respondents were interviewed (response rate 69.3%). The mean total knowledge score for the overall sample was 7.30 (SD ± 1.961) out of a possible score of 13 (Chinese had the highest scores, followed by Indians, then Malays). Some erroneous beliefs about the modes of transmission were identified. The majority of the participants (73.8%) perceived the A(H1N1) infection as often deadly. Despite the overestimation of the severity of A(H1N1) infection, high confidence in preventing infection and low perceived susceptibility of infection were reported. Influenza A(H1N1)-related stigma was prevalent and exhibited differences across ethnic groups. Findings suggest that provision of education and clear information are essential to correct the misconceptions, and increase perceived susceptibility to infection so that the general public will take precautions against A(H1N1) infection.

  17. In vitro Cytotoxicity Comparison of MTA Fillapex, AH-26 and Apatite Root Canal Sealer at Different Setting Times.

    Science.gov (United States)

    Jafari, Farnaz; Aghazadeh, Marzieh; Jafari, Sanaz; Khaki, Faraz; Kabiri, Fahime

    2017-01-01

    This study aimed to compare the cytotoxicity of MTA Fillapex, AH-26 and Apatite root canal sealers at different times after mixing. In this in vitro study, MTA Fillapex, AH-26 and Apatite root canal sealer were spilled uniformly by 40 µm mesh in a 96-well plate. Then, human fetal foreskin fibroblast cell line (HFFF2) were added to each sealer cell culture medium. Cytotoxicity was measured using MTT assay after 24, 48 and 72 h and seven days. Multiple comparisons were done using analysis of variances (ANOVA) and Scheffe's post hoc test. All studied sealers exhibited severe cytotoxicity (more than 70%) except for Apatite sealer (95%) at 48 h after mixing. Cytotoxicity of MTA Fillapex and AH-26 were similar (P>0.05) at 24, 48 and 72 h and 7 days after mixing of sealers. Cytotoxicity of MTA Fillapex and Apatite root canal sealer, at 24 and 48 h, were significantly different (P=0.003 and P=0.000, respectively); MTA Fillapex was more cytotoxic. However in 72 h and 7 days after mixing, the difference was not significant (P>0.05). At 24 and 48 h after mixing, AH-26 was more cytotoxic (P=0.002 and P=0.000, respectively). Same as above at 72 h and 7 days after mixing, their cytotoxicity were similar (P>0.05). Overall cytotoxicity of all studied materials were severe. However, it was observed that the cytotoxicity of MTA Fillapex, AH-26 and Apatite root canal sealer decreased over time. Apatite root canal sealer exhibited the least cytotoxicity. Cytotoxicity of MTA Fillapex and AH-26 were similar at different time intervals.

  18. Developing Maqasid al-Shari’ah Index to Evaluate Social Performance of Islamic Banks: A Conceptual and Empirical Attempt

    Directory of Open Access Journals (Sweden)

    Mehmet Asutay

    2015-07-01

    Full Text Available The rise of Islamic banking and finance is now a reality with Shari 'ah compliant financial operations existing in many different parts of the world. However, its development has recently been subjected to criticism in relation to the aspirational objectives of Islamic moral economy, which constitutes the moral foundations of Islamic finance. The aspirational objectives are general expressed with maqasid al-Shari'ah, which is defined as 'human well-being'.The aim of this research, hence, is to evaluate the social performance of Islamic banks according to maqasid al-Shari'ah upon the realization of Islamic Moral Economy aspirations. AbdelMajid Najjar's concept of maqasid al-Shari 'ah with eight orientations or articulations is adopted to construct an evaluation framework aligned with the objective of rendering a critical improvement of current empirical studies.In operationalizing the developed framework, this study conducts empirical investigations by taking 13 banks from 6 countries for 5-year period (2008-2012 as a sample. In doing so, the annual reports of the sampled banks for the period are subjected to content analysis to generate the necessary data in applying to the formulated framework.Empirical evidence indicates that there is lack of achievement in maqasid al-Shari 'ah performance of Islamic bank and finance. Nevertheless, the overall industry concentrates mainly on self, faith and rights and stakeholding rather than wealth orientation, despite the fewer contributions in social entity, intellect, posterity and ecology. Additionally, the empirical results find that there are different orientations across the banks and countries. Finally, the industry orientation is estimated in this research, which is located to be somewhere betweenfaith and rights and stakeholding.Keywords: Maqasid al-Shari 'ah, Islamic Banking and Finance, Evaluation, Performance

  19. Orbital Period Changes and Their Evolutionary Status for the Weak-Contact Binaries. III. AO Camelopardalis and AH Tauri

    Science.gov (United States)

    Yang, Y.-G.; Wei, J.-Y.; Kreiner, J. M.; Li, H.-L.

    2010-01-01

    In this paper, we presented multicolor photometric observations for two eclipsing binaries, AO Camelopardalis and AH Tauri, obtained on 2008 December 16 and 17. Using the Wilson-Devinney Code, the photometric solution of AH Tau was determined from our new CCD data. The mass ratio and the fill-out factor are q = 0.503(±0.003) and f = 10.8%(±0.1%), respectively. This indicates that AH Tau is in weak contact. For the weak-contact binary AO Cam, BVI light curves clearly show a difference in the heights of the maxima (i.e., the O'Connell effect), which may be explained by spot activity. By analyzing the O - C curves for AO Cam and AH Tau, it is found that the orbital periods appear to show a secular period decrease with a cyclic variation. The observed period modulation is ΔP/P ~ 10-6. For AO Cam, the cyclic oscillation with a short period of 7.63(±0.07) yr and a low amplitude of 0fd0019(±0fd0003) may be preferably attributed to the cyclic magnetic activity. The period and amplitude of the cyclic variation for AH Tau are 45.8(±1.1) yr and 0fd0171(±0fd0005), which may more likely result from the light-time effect via a third body. The secular period decrease rates are dP/dt = -1.26(±0.04) × 10-7 days yr -1 for AO Cam and dP/dt = -6.98(±0.07) × 10-8 days yr -1 for AH Tau. This kind of period decrease can be plausibly explained by the mass transfer from the primary to the secondary, and may result in the system evolving into a deep contact configuration.

  20. Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection

    Directory of Open Access Journals (Sweden)

    Eun Lee

    2011-08-01

    Full Text Available Purpose : The purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection. Methods : We retrospectively reviewed the charts of hospitalized pediatric patients (&lt;18 years diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010. Results : A total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years. A total of 40% had at least 1 underlying medical condition, including asthma (17%, malignancies (19%, and heart diseases (17%. Of the 72 patients, 54 (76% children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/ H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02, higher platelet count (P=0.02, and higher level of serum glucose (P=0.003, and more commonly presented with dyspnea than did those without pneumonia (P=0.04. Conclusion : No significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia.

  1. Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

    DEFF Research Database (Denmark)

    Haider, Najmul; Sturm-Ramirez, K.; Khan, S. U.;

    2017-01-01

    a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize...... and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5...

  2. A comparison of apical sealing ability between GuttaFlow and AH plus: An in vitro study

    OpenAIRE

    Patil, Prajakta; Rathore, Vishnu P. S.; Hotkar, Chetan; Savgave, Snehal S.; K. Raghavendra; Ingale, Priya

    2016-01-01

    Aims: The present study aimed to compare apical sealing ability between GuttaFlow and AH Plus. Materials and Method: Eighty extracted human maxillary anterior teeth with fully formed apex and straight root were collected for this study. The root canals were cleaned and shaped using a standard step back preparation to size 60# master apical file at the established working length and divided into four groups: Group 1, GuttaFlow sealer with gutta-percha; Group 2, AH Plus sealer with gutta-percha...

  3. Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

    Directory of Open Access Journals (Sweden)

    Béatrice Labrosse

    Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

  4. Real-Time Station Grouping under Dynamic Traffic for IEEE 802.11ah.

    Science.gov (United States)

    Tian, Le; Khorov, Evgeny; Latré, Steven; Famaey, Jeroen

    2017-07-04

    IEEE 802.11ah, marketed as Wi-Fi HaLow, extends Wi-Fi to the sub-1 GHz spectrum. Through a number of physical layer (PHY) and media access control (MAC) optimizations, it aims to bring greatly increased range, energy-efficiency, and scalability. This makes 802.11ah the perfect candidate for providing connectivity to Internet of Things (IoT) devices. One of these new features, referred to as the Restricted Access Window (RAW), focuses on improving scalability in highly dense deployments. RAW divides stations into groups and reduces contention and collisions by only allowing channel access to one group at a time. However, the standard does not dictate how to determine the optimal RAW grouping parameters. The optimal parameters depend on the current network conditions, and it has been shown that incorrect configuration severely impacts throughput, latency and energy efficiency. In this paper, we propose a traffic-adaptive RAW optimization algorithm (TAROA) to adapt the RAW parameters in real time based on the current traffic conditions, optimized for sensor networks in which each sensor transmits packets with a certain (predictable) frequency and may change the transmission frequency over time. The TAROA algorithm is executed at each target beacon transmission time (TBTT), and it first estimates the packet transmission interval of each station only based on packet transmission information obtained by access point (AP) during the last beacon interval. Then, TAROA determines the RAW parameters and assigns stations to RAW slots based on this estimated transmission frequency. The simulation results show that, compared to enhanced distributed channel access/distributed coordination function (EDCA/DCF), the TAROA algorithm can highly improve the performance of IEEE 802.11ah dense networks in terms of throughput, especially when hidden nodes exist, although it does not always achieve better latency performance. This paper contributes with a practical approach to optimizing

  5. Effects of Bt-cry1Ah corn pollen on larvae of Apis mellifera ligustica%转Bt-cry1Ah基因玉米花粉对意大利蜜蜂幼虫的影响

    Institute of Scientific and Technical Information of China (English)

    代平礼; 周玮; 张杰; 郎志宏; 周婷; 王强; 崔红娟; 姜玮瑜; 吴艳艳

    2012-01-01

    The cry1Ah gene, which displays high toxicity against Lepidopteran larvae, was one of the novel insecticidal genes cloned from Bacillus thuringiensis isolate BT8. Cry1Ah protein have higher toxicity to the Asian corn borer ( Ostrinia furnacalis( Guen6e) ) than any other cry1A genes. The crylAh gene was therefore a candidate gene for insect resistant transgenic corn research. Pollen is a significant component of the diet of honeybees. Thus the honeybee may serve as one of the key species to be tested for the potential adverse effects of transgenic crops and assessment of impacts on honeybees is an essential part of the risk assessment process for Bt cry1Ah gene corn. The effects of dietary transgenic Bt corn pollen on honeybee worker larvae of Apis mellifera ligustica Spinola was examined. We measured cap rate, emergence rate, and immature stage after 4-6-day-old larvae were fed either crylAh corn pollen, regular corn pollen, mixed bee pollen and a control. There were no significant differences in all the parameters measured between bees fed these diets. These results suggest that transgenic Bt corn pollen does not pose a threat to honeybee larval development.%新型杀虫蛋白基因crylAh基因是中国农业科学院植物保护研究所从Bt菌株BT8中鉴定克隆的,其编码蛋白对鳞翅目害虫具有强毒力,尤其对亚洲玉米螟Ostrinia furnacalis(Guenée)的毒力强于目前使用的cry1A类基因.转cry1Ah基因抗虫玉米具有很好的应用前景.花粉是蜜蜂重要的食物来源,蜜蜂是转基因植物安全性评价的关键测试生物.因此,开展转crylAh基因玉米对蜜蜂的安全性研究很有必要.给意大利蜜蜂Apis mellifera ligustica Spinola蜂群中4~6日龄幼虫饲喂转基因玉米花粉、常规玉米花粉、杂花粉,哺育蜂饲喂为对照.转基因玉米花粉对意大利蜜蜂封盖率、出房率和发育历期没有显著影响.表明转cry1Ah基因玉米花粉对意大利蜜蜂幼虫的存活和发育没有不良影响.

  6. Using high-throughput sequencing to leverage surveillance of genetic diversity and oseltamivir resistance: a pilot study during the 2009 influenza A(H1N1 pandemic.

    Directory of Open Access Journals (Sweden)

    Juan Téllez-Sosa

    Full Text Available BACKGROUND: Influenza viruses display a high mutation rate and complex evolutionary patterns. Next-generation sequencing (NGS has been widely used for qualitative and semi-quantitative assessment of genetic diversity in complex biological samples. The "deep sequencing" approach, enabled by the enormous throughput of current NGS platforms, allows the identification of rare genetic viral variants in targeted genetic regions, but is usually limited to a small number of samples. METHODOLOGY AND PRINCIPAL FINDINGS: We designed a proof-of-principle study to test whether redistributing sequencing throughput from a high depth-small sample number towards a low depth-large sample number approach is feasible and contributes to influenza epidemiological surveillance. Using 454-Roche sequencing, we sequenced at a rather low depth, a 307 bp amplicon of the neuraminidase gene of the Influenza A(H1N1 pandemic (A(H1N1pdm virus from cDNA amplicons pooled in 48 barcoded libraries obtained from nasal swab samples of infected patients (n  =  299 taken from May to November, 2009 pandemic period in Mexico. This approach revealed that during the transition from the first (May-July to second wave (September-November of the pandemic, the initial genetic variants were replaced by the N248D mutation in the NA gene, and enabled the establishment of temporal and geographic associations with genetic diversity and the identification of mutations associated with oseltamivir resistance. CONCLUSIONS: NGS sequencing of a short amplicon from the NA gene at low sequencing depth allowed genetic screening of a large number of samples, providing insights to viral genetic diversity dynamics and the identification of genetic variants associated with oseltamivir resistance. Further research is needed to explain the observed replacement of the genetic variants seen during the second wave. As sequencing throughput rises and library multiplexing and automation improves, we foresee that

  7. Measurements of Electric Performance and Impedance of a 75 Ah NMC Lithium Battery Module

    DEFF Research Database (Denmark)

    Jensen, Søren Højgaard; Engelbrecht, Kurt

    2012-01-01

    Detailed characterization of battery modules is necessary to construct reliable models that incorporate performance related aspects of the modules such as thermodynamics, electrochemical reaction kinetics and degradation mechanisms. Charge-discharge curves, temperature and battery impedance...... measurements can provide information about these aspects. Charge-discharge curves can be used to measure the battery open circuit voltage and the internal resistance. Temperature measurements provide information about the thermodynamic reactions and impedance spectra yield detailed information about...... the reaction kinetics. In this paper we present the measurement methods used to examine the internal resistance, the capacity and the impedance of a 75 Ah NMC battery module. In order to measure the impedance of the battery module and of the individual cells in the module, we combine the single sine technique...

  8. The Political Economy of Sunni-Shi’ah Conflict in Sampang Madura

    Directory of Open Access Journals (Sweden)

    Masdar Hilmy

    2015-06-01

    Full Text Available Many overlooked the fact that politico-economic factors played an important role behind the 2011 and 2012 Sunni-Shi’ah conflict in Sampang Madura. Some, however, argue that the Sunni-Shi’ah conflict was merely driven by theological factors. The major roots of the conflict thus were therefore the internal dimensions of religious beliefs as contained in its doctrines. As a result, the conflict can only be explained in terms of religious and theological framework. This assumption is commonly shared by the majority of Madurese Muslims by arguing that the island of Madura cannot host the believers of non-Sunni. In the aftermath of the conflict, the community of Shi’ah has been forced to seek refuge outside of the land of Madura. By doing so, many observers and the Madurese Muslims tends to have treated political and economic factors as peripheral that exacerbated the escalation of conflict. This article, however, argues vice-versa that it is not theology, but politics and economy, which mainly steered the conflict. Theology played a role in exacerbating the escalation of conflict. During the conflict, religious and theological arguments were deployed as a mobilizing force in order to justify the conflict. Furthermore, the existence of Shi’ah community in Sampang is regarded by the mainstream Sunni community as a threat to their long domination over the socio-political structure in that region. The paper, thus, perceives the conflict as the way the local elites maintain the established mode of production. This paper is qualitative research that employs political-economy as its main approach in analyzing the data. [Para pengamat banyak tidak melihat aktor politik dan ekonomi di balik konflik Sunni dan Syiah 2011 dan 2012 di Sampang Madura. Para peneliti bahkan beranggapan bahwa konflik Sunni-Syiah itu dilatari oleh faktor teologis. Ini artinya bahwa tiap kelompok memegang sistem kepercayaan yang berbeda. Akar utama dari konflik itu pada

  9. Thermoelectrochemical simulations of performance and abuse in 50-Ah automotive cells

    Science.gov (United States)

    Kim, Sun Ung; Albertus, Paul; Cook, David; Monroe, Charles W.; Christensen, Jake

    2014-12-01

    The performance and thermal response of large-scale GS-Yuasa LEV50 50-Ah NMC automotive battery cells were investigated via simulation. To evaluate local transient temperature distributions, the Dualfoil model was coupled to local energy-balance equations. At similar C rates the difference between maximum and minimum temperature in the LEV50 was found to be higher than that in an 18650 cell with identical chemistry. Unlike thinner prismatic lithium ion batteries, the temperature variation through the cell thickness in the large-format cell was not negligible (∼5 °C at 4C discharge). Because of the non-uniform temperature distribution within the jellyroll, the risk of lithium plating at high charging rates and low ambient temperatures may be greater toward the jellyroll exterior. Simulations of thermal abuse (oven test) of the large cell showed a delayed thermal response relative to the 18650, but also indicated a lower onset temperature for thermal runaway.

  10. Student behavior during a school closure caused by pandemic influenza A/H1N1.

    Directory of Open Access Journals (Sweden)

    Joel C Miller

    Full Text Available BACKGROUND: Many schools were temporarily closed in response to outbreaks of the recently emerged pandemic influenza A/H1N1 virus. The effectiveness of closing schools to reduce transmission depends largely on student/family behavior during the closure. We sought to improve our understanding of these behaviors. METHODOLOGY/PRINCIPAL FINDINGS: To characterize this behavior, we surveyed students in grades 9-12 and parents of students in grades 5-8 about student activities during a week long closure of a school during the first months after the disease emerged. We found significant interaction with the community and other students-though less interaction with other students than during school-with the level of interaction increasing with grade. CONCLUSIONS: Our results are useful for the future design of social distancing policies and to improving the ability of modeling studies to accurately predict their impact.

  11. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...... initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization...... and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17...

  12. A Comparative Study Between Two Translation Versions of the Real Story of Ah Q

    Institute of Scientific and Technical Information of China (English)

    赖寒

    2014-01-01

    Lu Xun has been regared as a great writer, thinker and reformer in China’s modern times. He excelled in creating short stories and essays to attack the social evils. His style can be characterized as conciseness and harsh irony. The real story of Ah Q is one of his representative work of short stories from the short story collection“Call to Arms”.This paper aims to ana-lyze and compare two translation versions given by the Chinese couple translators Yang Xianyi and American translator William A. Lyell through two aspects, namely translation purpose and translation standard so as to lay a good foundation for further study of translating Lu Xun’s short stories.

  13. Sharī’ah and the Politics of Pluralism in Indonesia

    Directory of Open Access Journals (Sweden)

    Ratno Lukito

    2007-08-01

    Full Text Available Keeping in mind the Indonesian Government's policy regarding legal pluralism, this article will take a closer look at how the Government deals with the existence of both Islamic law and customary law (adat. The adoption of "state law pluralism", especially by the New Order regime since 1970s, has had an evident impact on the way the state handles the institution of adat and Islamic law (shari'ah. The question is what is the motive behind employing this strategy? This is a question that necessitates more a socio-political approach in the study of comparative law, drawing on a number of regulations and acts related to adat and Islamic law as the primary sources.Copyright (c 2014 by SDI. All right reserved.DOI: 10.15408/sdi.v14i2.545

  14. The AhR is involved in the regulation of LoVo cell proliferation through cell cycle-associated proteins.

    Science.gov (United States)

    Yin, Jiuheng; Sheng, Baifa; Han, Bin; Pu, Aimin; Yang, Kunqiu; Li, Ping; Wang, Qimeng; Xiao, Weidong; Yang, Hua

    2016-05-01

    Some ingredients in foods can activate the aryl hydrocarbon receptor (AhR) and arrest cell proliferation. In this study, we hypothesized that 6-formylindolo [3, 2-b] carbazole (FICZ) arrests the cell cycle in LoVo cells (a colon cancer line) through the AhR. The AhR agonist FICZ and the AhR antagonist CH223191 were used to treat LoVo cells. Real-time PCR and Western blot analyses were performed to detect the expression of the AhR, CYP1A1, CDK4, cyclinD1, cyclin E, CDK2, P27, and pRb. The distribution and activation of the AhR were detected with immunofluorescence. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometric analysis were performed to measure cell viability, cell cycle stage, and apoptosis. Our results show that FICZ inhibited LoVo cell proliferation by inducing G1 cell cycle arrest but had no effect on epithelial apoptosis. Further analysis found that FICZ downregulated cyclinD1 and upregulated p27 expression to arrest Rb phosphorylation. The downregulation of cyclinD1 and upregulation of p27 were abolished by co-treatment with CH223191. We conclude that the AhR, when activated by FICZ (an endogenous AhR ligand), can arrest the cell cycle and block LoVo cell proliferation.

  15. Effectiveness of the influenza A(H1N1)PDM09 vaccine in adults recommended for annual influenza vaccination: A matched case-control study

    NARCIS (Netherlands)

    Gefenaite, Giedre; Tacken, Margot; Bos, Jens; Stirbu-Wagner, Irina; Korevaar, Joke C.; Stolk, Ronald P.; Wolters, Bert; Bijl, Marc; Postma, Maarten J.; Wilschut, Jan; Nichol, Kristin L.; Hak, Eelko

    2012-01-01

    Background and objectives Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we aimed to assess the effectiveness of MF59-adjuvanted A(H1N1)pdm09 vaccine in a matched case-control study. Patients/methods This study was conducted during the pandemic influenza

  16. Influence of TCDD and natural Ah receptor agonists on benzo[a]pyrene-DNA adduct formation in the Caco-2 human colon cell line

    NARCIS (Netherlands)

    Waard, de W.J.; Kok, de T.M.C.M.; Maas, L.M.; Peijnenburg, A.A.C.M.; Hoogenboom, L.A.P.; Aarts, H.J.M.; Schooten, van F.J.

    2008-01-01

    Several compounds originating from cruciferous vegetables and citrus fruits bind to and activate the aryl hydrocarbon receptor (AhR). This receptor plays an important role in the toxicity of the known tumour promoter and potent AhR-agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, vegetab

  17. A comparison of rapid point-of-care tests for the detection of avian influenza A(H7N9) virus, 2013

    NARCIS (Netherlands)

    C. Baas (Chantal); I.G. Barr (Ian); R.A.M. Fouchier (Ron); A. Kelso; A.C. Hurt (Aeron)

    2013-01-01

    textabstractSix antigen detection-based rapid influenza point-of-care tests were compared for their ability to detect avian influenza A(H7N9) virus. The sensitivity of at least four tests, standardised by viral infectivity (TCID50) or RNA copy number, was lower for the influenza A(H7N9) virus than f

  18. Start of the 2014/2015 influenza season in Europe: drifted influenza A(H3N2) viruses circulate as dominant subtype.

    NARCIS (Netherlands)

    Broberg, E.; Snacken, R.; Aldhoch, C.; Beauté, J.; Galinksa, M.; Pereyaslov, D.; Brown, C.; Penttinen, P.

    2015-01-01

    The influenza season 2014/15 started in Europe in week 50 2014 with influenza A(H3N2) viruses predominating. The majority of the A(H3N2) viruses characterised antigenically and/or genetically differ from the northern hemisphere vaccine component which may result in reduced vaccine effectiveness for

  19. Reliable and Efficient Access for Alarm-initiated and Regular M2M Traffic in IEEE 802.11ah Systems

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales; Stefanovic, Cedomir; Popovski, Petar

    2016-01-01

    IEEE 802.11ah is a novel WiFi-based protocol, aiming to provide an access solution for the machine-to-machine (M2M) communications. In this paper, we propose an adaptive access mechanism that can be seamlessly incorporated into IEEE 802.11ah protocol operation and that supports all potential M2M...

  20. Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010

    NARCIS (Netherlands)

    Meijer, Adam; Jonges, Marcel; Abbink, Floor; Ang, Wim; van Beek, Janko; Beersma, Matthias; Bloembergen, Peter; Boucher, Charles; Claas, Eric; Donker, Ge; van Gageldonk-Lafeber, Rianne; Isken, Leslie; Kroes, Aloys; Leenders, Sander; van der Lubben, Mariken; Mascini, Ellen; Niesters, Bert; Oosterheert, Jan Jelrik; Osterhaus, Albert; Riesmeijer, Rob; Riezebos-Brilman, Annelies; Schutten, Martin; Sebens, Fre; Stelma, Foekje; Swaan, Corien; Timen, Aura; van 't Veen, Annemarie; van der Vries, Erhard; Wierik, Margreet Te; Koopmans, Marion; de Jong, A

    2011-01-01

    Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 200

  1. Penciptaan Lingkungan Edukatif dalam Pembentukan Karakter: Studi terhadap Aplikasi Pemikiran Ibnu Jama’ah

    Directory of Open Access Journals (Sweden)

    Hery Noer Aly

    2012-04-01

    Full Text Available This study is a rediscovery enterprise on educational thought of Ibn Jama’ah in his famous book, al-Tadhkirah. It is basically the book on  learning and teaching. But, much more  than a book on  technic and strategy ,  it  is  full of  moral message which conducts whole process of  learning and  teaching,  and  in  turn  creates an  educating environment. The significance of this study due to moral decadence among the nation. Corruption, for instance, is not only available among the leaders and bureaucrates, but also among the peoples. Delinquency  is not only the habit of  young generation, but now suffered by parents who can not give a good sample. That moral decadence is not deal with  the poverty of moral conduct; there  are  treasury  and haritage of  it, either from religous or traditional resource. But that old values available in many documents are not internalized yet, in additon to the fast-coming of foreign culture which is not in accord with Indonesian culture. Here we see that the issue is not the content of value education, but the strategy developed  in the process. So that, al-Tadhkirah will be studied with content analysis approach to find out the possibility of application of his thought in moral education. The study  finally discovered that the  thought of  Ibn  Jama’ah  is very possible  to be applied. The only precondition  is the commitment of all stakeholders to create educating environtment based on regulation formulated by themselves.

  2. Multiple Myeloma and Glyphosate Use: A Re-Analysis of US Agricultural Health Study (AHS) Data

    Science.gov (United States)

    Sorahan, Tom

    2015-01-01

    A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993–2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use. PMID:25635915

  3. Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study (AHS) data.

    Science.gov (United States)

    Sorahan, Tom

    2015-01-28

    A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993-2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use.

  4. Problematika Pendidikan Islam Perspektif Maqâṣid Sharîʻah

    Directory of Open Access Journals (Sweden)

    Rosidin Rosidin

    2016-11-01

    Full Text Available The article seeks to reveal problems faced by Islamic education from the perspective of Maqâṣid al-Sharîʻah, namely ideological (h}ifẓ al-dîn, practical (h}ifẓ al-nafs, academic (h}ifẓ al-‘aql, relationships or networks (h}ifẓ al-nasl, vocational (h}ifẓ al-mâl and quality (h}ifẓ al-‘irḍ aspects. In order to know the details of crucial problems of the Islamic education along with their alternative solutions, this paper suggests that the Islamic education should consider the insider’s and outsider’s perspective which has four types of roles as follow: a complete observer; b observer as participant; c participant as observer; d complete participant. This article proposes three important implications, are: first, the problems of the Islamic education can be categorized and mapped based on Maqâṣid al-Sharîʻah, in order to ease the analysis of such problems. Second, the analysis of the problems should be based on the insiders’ and outsiders’ point of views, so that it would be able to comprehensively detect the problems of Islamic education and show the inclusiveness of the Islamic education. Third, problem solving alternatives should be oriented at the level of theological (faith and religious [îmân], theoretical (philosophical and empirical [‘ilm], practical (learning and teaching [‘amal] and moral (ethics and aesthetics [akhlâq] realms.

  5. Multiple Myeloma and Glyphosate Use: A Re-Analysis of US Agricultural Health Study (AHS Data

    Directory of Open Access Journals (Sweden)

    Tom Sorahan

    2015-01-01

    Full Text Available A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS produced disparate findings in relation to multiple myeloma risks in the period 1993–2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR 1.1, 95% confidence interval (CI 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4. It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49 for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94. There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use.

  6. Effects of currently used pesticides in the AhR-CALUX assay: comparison between the human TV101L and the rat H4IIE cell line

    DEFF Research Database (Denmark)

    Long, Manhai; Laier, Peter; Vinggaard, Anne Marie

    2003-01-01

    to be a rapid and sensitive assay for assessing the potency of AhR-activating compounds. We have used the AhR-CALUX assay to investigate the AhR-mediated activity of the persistent organochlorine insecticide dieldrin and twenty-two pesticides currently used in Denmark by employing the rat H4IIE and the human TV......101L hepatoma cell lines. In comparison the results indicated that the rat H4IIE cell line is more sensitive than the human TV101L for detection of TCDD inducing AhR-CALUX activity. The pesticides iprodione, chlorpyrifos and prochloraz showed dose-dependent AhR agonistic effects in both cell lines...... at concentrations above 10, 1 and 1 microM, respectively. However, some pesticides (methiocarb, chlorothalonil, tribenuron-methyl, paclobutrazol and tolchlofos-methyl) elicited differential responses in the two cell lines....

  7. Influenza A(H1N1) oseltamivir resistant viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Dijkstra, F.; Jonges, M.; Beek, R. van; Donker, G.A.; Schellevis, F.G.; Koopmans, M.; Sande, M.A.B. van der; Osterhaus, A.D.M.E.; Boucher, C.A.B.; Rimmelzwaan, G.F.; Meijer, A.

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was pe

  8. Molecular epidemiology of influenza A/H3N2 viruses circulating in Mexico from 2003 to 2012.

    Directory of Open Access Journals (Sweden)

    Marina Escalera-Zamudio

    Full Text Available In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.

  9. Criteria of Shari'ah supervisory committee: A comparative study between guidelines of Bangladesh Bank and Bank Negara Malaysia

    National Research Council Canada - National Science Library

    Muhammad Amanullah

    2015-01-01

    .... Likewise, Bank Negara Malaysia has provided some guidelines. The main objectives of this research paper are to highlight the guidelines of these two banks on these criteria, compare them and evaluate them in light of Shari'ah guidelines on these criteria spelled out by contemporary Muslim jurists.

  10. Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

    Science.gov (United States)

    Helanterä, I; Anttila, V-J; Lappalainen, M; Lempinen, M; Isoniemi, H

    2015-09-01

    Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients.

  11. Developing Islamic Banking Performance Measures Based on Maqasid Al-Shari’ah Framework: Cases of 24 Selected Banks

    Directory of Open Access Journals (Sweden)

    Mustafa Omar Mohammed

    2015-08-01

    Full Text Available Islamic banking has achieved remarkable growth that has surpassed the growth of the conventional banking system. Yet, studies show that the performances of Islamic banks (IBs seem to be trailing behind the conventional banks (CBs. Is the poor performance of IBs the result of mismatch between their objectives and their performance measurement criteria or it is a reflection of their true performances? The objectives of Islamic banking had not been formally addressed. Mustafa and Taib (2009 derived the objectives of Islamic banking from Abu Zahara’s theory of the objectives of Shari’ah (Maqasid al-Shari’ah and, based on these Shari’ah objectives, developed a model of Islamic banking performance measures. They named it as Performance Measures based on Maqasid al-Shari’ah framework or the PMMS model. This paper has tested the PMMS model on a sample 24 banks (12 IBs and 12 CBs. The twenty four banks were also evaluated using the traditional conventional financial measures. Mann-Whitney U-Test results show IBs faring well in their performances when measured using the PMMS model than when they are measured using the conventional banking performance yardstick. Policy prescriptions and recommendations for further studies are provided at the concluding section of the paper.

  12. Influenza A(H1N1) oseltamivir resistant viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Dijkstra, F.; Jonges, M.; Beek, R. van; Donker, G.A.; Schellevis, F.G.; Koopmans, M.; Sande, M.A.B. van der; Osterhaus, A.D.M.E.; Boucher, C.A.B.; Rimmelzwaan, G.F.; Meijer, A.

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was pe

  13. Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Pedersen, Svend Stenvang; Vorborg, Kristine

    2017-01-01

    Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient...

  14. Estimating the Distribution of the Incubation Periods of Human Avian Influenza A(H7N9) Virus Infections

    Science.gov (United States)

    Virlogeux, Victor; Li, Ming; Tsang, Tim K.; Feng, Luzhao; Fang, Vicky J.; Jiang, Hui; Wu, Peng; Zheng, Jiandong; Lau, Eric H. Y.; Cao, Yu; Qin, Ying; Liao, Qiaohong; Yu, Hongjie; Cowling, Benjamin J.

    2015-01-01

    A novel avian influenza virus, influenza A(H7N9), emerged in China in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. The distribution of A(H7N9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. Imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incubation times of approximately 5 days. In this study, we estimated the incubation period distribution of human influenza A(H7N9) infections using exposure data available for 229 patients with laboratory-confirmed A(H7N9) infection from mainland China. A nonparametric model (Turnbull) and several parametric models accounting for the interval censoring in some exposures were fitted to the data. For the best-fitting parametric model (Weibull), the mean incubation period was 3.4 days (95% confidence interval: 3.0, 3.7) and the variance was 2.9 days; results were very similar for the nonparametric Turnbull estimate. Under the Weibull model, the 95th percentile of the incubation period distribution was 6.5 days (95% confidence interval: 5.9, 7.1). The midpoint approximation for interval-censored exposures led to overestimation of the mean incubation period. Public health observation of potentially exposed persons for 7 days after exposure would be appropriate. PMID:26409239

  15. Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Mexico from 2003 to 2012

    Science.gov (United States)

    Escalera-Zamudio, Marina; Nelson, Martha I.; Cobián Güemes, Ana Georgina; López-Martínez, Irma; Cruz-Ortiz, Natividad; Iguala-Vidales, Miguel; García, Elvia Rodríguez; Barrera-Badillo, Gisela; Díaz-Quiñonez, Jose Alberto; López, Susana; Arias, Carlos F.; Isa, Pavel

    2014-01-01

    In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America. PMID:25075517

  16. Historical Prevalence and Distribution of Avian Influenza Virus A(H7N9) among Wild Birds

    Centers for Disease Control (CDC) Podcasts

    2013-12-19

    Dr. Mike Miller reads an abridged version of the Emerging Infectious Diseases’ dispatch, Historical Prevalence and Distribution of Avian Influenza Virus A(H7N9) among Wild Birds.  Created: 12/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 12/24/2013.

  17. Narcolepsy and A(H1N1)pdm09 vaccination: shaping the research on the observed signal.

    Science.gov (United States)

    van der Most, Robbert; Van Mechelen, Marcelle; Destexhe, Eric; Wettendorff, Martine; Hanon, Emmanuel

    2014-01-01

    Epidemiological data from several European countries suggested an increased risk of the chronic sleep disorder narcolepsy following vaccination with Pandemrix(™), an AS03-adjuvanted, pandemic A(H1N1)pdm09 influenza vaccine. Further research to investigate potential associations between Pandemrix™ vaccination, A(H1N1)pdm09 influenza infection and narcolepsy is required. Narcolepsy is most commonly caused by a reduction or absence of hypocretin produced by hypocretin-secreting neurons in the hypothalamus, and is tightly associated with HLA-II DQB1*06:02. Consequently, research focusing on CD4(+) T-cell responses, building on the hypothesis that for disease development, T cells specific for antigen(s) from hypocretin neurons must be activated or reactivated, is considered essential. Therefore, the following key areas of research can be identified, (1) characterization of hypothetical narcolepsy-specific auto-immune CD4(+) T cells, (2) mapping epitopes of such T cells, and (3) evaluating potential mechanisms that would enable such cells to gain access to the hypothalamus. Addressing these questions could further our understanding of the potential links between narcolepsy and A(H1N1)pdm09 vaccination and/or infection. Of particular interest is that any evidence of a mimicry-based mechanism could also explain the association between narcolepsy and A(H1N1)pdm09 influenza infection.

  18. A/H1N1 Vaccine Intentions in College Students: An Application of the Theory of Planned Behavior

    Science.gov (United States)

    Agarwal, Vinita

    2014-01-01

    Objective: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. Participants: Undergraduate communication students at a metropolitan southern university. Methods: In January-March 2010, students from voluntarily participating communication classes completed a…

  19. A/H1N1 Vaccine Intentions in College Students: An Application of the Theory of Planned Behavior

    Science.gov (United States)

    Agarwal, Vinita

    2014-01-01

    Objective: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. Participants: Undergraduate communication students at a metropolitan southern university. Methods: In January-March 2010, students from voluntarily participating communication classes completed a…

  20. SPATIOTEMPORAL TRENDS OF CASES OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN ARGENTINA, 2009-2012

    Science.gov (United States)

    LEVEAU, Carlos M.; UEZ, Osvaldo; VACCHINO, Marta N.

    2015-01-01

    The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies. PMID:25923892

  1. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Davey, Richard T; Lynfield, Ruth; Dwyer, Dominic E

    2013-01-01

    Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were...

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

    Science.gov (United States)

    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.

  3. Identification of ah receptor agonists in soil of E-waste recycling sites from Taizhou area in China.

    Science.gov (United States)

    Shen, Chaofeng; Huang, Shengbiao; Wang, Zijian; Qiao, Min; Tang, Xianjin; Yu, Chunna; Shi, Dezhi; Zhu, Youfeng; Shi, Jiyan; Chen, Xincai; Setty, Karen; Chen, Yingxu

    2008-01-01

    In recent years, increasing concern has surrounded the consequences of improper electric and electronic waste (e-waste) disposal. In order to mitigate or remediate the potentially severe toxic effects of e-waste recycling on the environment, organisms, and humans, many contaminated sites must first be well-characterized. In this study, soil samples were taken from Taizhou city, one of the largest e-waste disposal centers in China, which was involved in recycling for nearly 30 years. The extracts of the samples were assayed for aryl hydrocarbon receptor (AhR)-mediated ethoxyresorufin-O-deethylase (EROD) induction in the rat hepatoma cell line H4IIE. Some of the target AhR agonists, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs), were instrumentally analyzed as well. The cause-effect relationship and dose-response relationship between the chemical concentrations of AhR agonists and observed EROD activity were examined. The results showed that soil extracts could induce AhR activity significantly, and the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQcal) were perfectly correlated to bioassay-derived TCDD equivalents (TEQbio; R = 0.96, P electric power devices and open burning of electric wires and printed circuit boards may be the main sources of these dioxin-like compounds. This study suggests that the combination of in vitro bioassay and chemical analysis is useful to screen, identify, and prioritize AhR agonists in soil from e-waste recycling areas.

  4. Clinical severity of human infections with avian influenza A(H7N9) virus, China, 2013/14.

    Science.gov (United States)

    Feng, L; Wu, J T; Liu, X; Yang, P; Tsang, T K; Jiang, H; Wu, P; Yang, J; Fang, V J; Qin, Y; Lau, E H; Li, M; Zheng, J; Peng, Z; Xie, Y; Wang, Q; Li, Z; Leung, G M; Gao, G F; Yu, H; Cowling, B J

    2014-12-11

    Assessing the severity of emerging infections is challenging because of potential biases in case ascertainment. The first human case of infection with influenza A(H7N9) virus was identified in China in March 2013; since then, the virus has caused two epidemic waves in the country. There were 134 laboratory-confirmed cases detected in the first epidemic wave from January to September 2013. In the second epidemic wave of human infections with avian influenza A(H7N9) virus in China from October 2013 to October 2014, we estimated that the risk of death among hospitalised cases of infection with influenza A(H7N9) virus was 48% (95% credibility interval: 42-54%), slightly higher than the corresponding risk in the first wave. Age-specific risks of death among hospitalised cases were also significantly higher in the second wave. Using data on symptomatic cases identified through national sentinel influenza-like illness surveillance, we estimated that the risk of death among symptomatic cases of infection with influenza A(H7N9) virus was 0.10% (95% credibility interval: 0.029-3.6%), which was similar to previous estimates for the first epidemic wave of human infections with influenza A(H7N9) virus in 2013. An increase in the risk of death among hospitalised cases in the second wave could be real because of changes in the virus, because of seasonal changes in host susceptibility to severe infection, or because of variation in treatment practices between hospitals, while the increase could be artefactual because of changes in ascertainment of cases in different areas at different times.

  5. Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey

    Directory of Open Access Journals (Sweden)

    Blumental Sophie

    2011-11-01

    Full Text Available Abstract Background During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. Methods From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR and probable (positive influenza A antigen or culture pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. Results During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%, concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002 and a higher mortality rate (4% vs 0%, p = 0.06. Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. Conclusion Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

  6. Differences in the pathogenicity and inflammatory responses induced by avian influenza A/H7N9 virus infection in BALB/c and C57BL/6 mouse models.

    Directory of Open Access Journals (Sweden)

    Guangyu Zhao

    Full Text Available Avian influenza A/H7N9 virus infection causes pneumonia in humans with a high case fatality rate. However, virus-induced modulation of immune responses is being recognized increasingly as a factor in the pathogenesis of this disease. In this study, we compared the pathogenicity of A/H7N9 infection in BALB/c and C57BL/6 mouse models, and investigated the putative involvement of proinflammatory cytokines in lung injury and viral clearance. In both mouse strains, A/Anhui/1/2013(H7N9 infection with 10(6 TCID50 resulted in viral replication in lung, severe body weight loss and acute lung injury. During the early infection stage, infected C57BL/6 mice exhibited more severe lung injury, slower recovery from lung damage, less effective viral clearance, higher levels of interlukine (IL-6, monocyte chemotactic protein (MCP-1, and IL-1β, and lower levels of tumor necrosis factor (TNF-α and interferon (IFN-γ than infected BALB/c mice. These results suggest that TNF-α and IFN-γ may help suppress viral gene expression and increase viral clearance, and that IL-6 and MCP-1 may contribute to lung injury in A/H7N9-infected individuals. In addition, lung damage and the distribution of virus antigen in tissues were similar in young and middle-aged mice. These results suggest that the more serious lung injury in middle-aged or older H7N9 cases is not mainly caused by differences in viral replication in the lung but probably by a dysregulated immune response induced by underlying comorbidities. These results indicate that the extent of dysregulation of the host immune response after H7N9 virus infection most probably determines the outcome of H7N9 virus infection.

  7. 3-Methylcholanthrene, an AhR agonist, caused cell-cycle arrest by histone deacetylation through a RhoA-dependent recruitment of HDAC1 and pRb2 to E2F1 complex.

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Chang

    Full Text Available We previously showed that treating vascular endothelial cells with 3-methylcholanthrene (3MC caused cell-cycle arrest in the Go/G1 phase; this resulted from the induction of p21 and p27 and a decreased level and activity of the cyclin-dependent kinase, Cdk2. We further investigated the molecular mechanisms that modulate cell-cycle regulatory proteins through the aryl-hydrocarbon receptor (AhR/Ras homolog gene family, member A (RhoA dependent epigenetic modification of histone. AhR/RhoA activation mediated by 3MC was essential for the upregulation of retinoblastoma 2 (pRb2 and histone deacetylase 1 (HDAC1, whereas their nuclear translocation was primarily modulated by RhoA activation. The combination of increased phosphatase and tensin homolog (PTEN activity and decreased phosphatidylinositide 3-kinase (PI3K activation by 3MC led to the inactivation of the Ras-cRaf pathway, which contributed to pRb2 hypophosphorylation. Increased HDAC1/pRb2 recruitment to the E2F1 complex decreased E2F1-transactivational activity and H3/H4 deacetylation, resulting in the downregulation of cell-cycle regulatory proteins (Cdk2/4 and Cyclin D3/E. Co-immunoprecipitation and electrophoretic mobility shift assay (EMSA results showed that simvastatin prevented the 3MC-increased binding activities of E2F1 proteins in their promoter regions. Additionally, RhoA inhibitors (statins reversed the effect of 3MC in inhibiting DNA synthesis by decreasing the nuclear translocation of pRb2/HDAC1, leading to a recovery of the levels of cell-cycle regulatory proteins. In summary, 3MC decreased cell proliferation by the epigenetic modification of histone through an AhR/RhoA-dependent mechanism that can be rescued by statins.

  8. Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH em pacientes com diabete melito tipo 1 Platelet-activating factor acetylhydrolase (PAF-AH activity in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Simone Henriques de Castro

    2007-02-01

    Full Text Available OBJETIVO: Avaliar a atividade da acetil-hidrolase do fator ativador de plaquetas (PAF-AH e sua relação com variáveis clinicodemográficas, com o controle metabólico, os níveis de apolipoproteínas A e B e a suscetibilidade da lipoproteína de baixa densidade (LDL à oxidação in vitro em pacientes com DM tipo 1 (DM 1. MÉTODOS: Foram avaliados 42 pacientes com DM1 (27 mulheres e 48 não-diabéticos (16 mulheres, pareados por sexo, idade e índice de massa corporal (IMC. Os exames realizados foram: glicemia de jejum (GJ e pós-prandial (GPP, lipidograma, ácido úrico (AU, hemoglobina glicosilada (HbA1c e coeficiente de oxidação da lipoproteína de baixa densidade (LDL por espectrofotometria. A análise da atividade da PAF-AH foi realizada por espectrofotometria (Cayman Chemical. RESULTADOS: A análise da atividade da PAF-AH mostrou haver maior atividade enzimática nos pacientes com DM 1 do que nos não-diabéticos (0,0150 ± 0,0051 versus 0,0116 ± 0,0041; p OBJECTIVE: To evaluate platelet-activating factor acetylhydrolase (PAF-AH activity and its relationship with clinical and demographic variables, metabolic control, apolipoprotein A and B levels and the susceptibility of low-density lipoprotein (LDL to in vitro oxidation in patients with type 1 diabetes mellitus (DM 1. METHODS: Forty two patients with DM 1 (27 females and 48 control subjects (16 females matched for gender, age and body mass index (BMI were evaluated. The following tests were performed: fast plasma glucose (FG and postprandial plasma glucose (PPG, lipid profile, uric acid (UA, glycosylated hemoglobin (HbA1c, and low-density lipoprotein (LDL oxidation rate using colorimetric assay. The PAF-AH activity was analyzed using colorimetric assay (Cayman Chemical. RESULTS: The analysis of PAF-AH activity showed a higher enzyme activity in patients with DM 1 than in control subjects (0.0150 ± 0.0051 vs. 0.0116 ± 0.0041; p < 0.001. In patients with DM 1, a direct correlation

  9. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses.

    Science.gov (United States)

    Butler, Jeff; Hooper, Kathryn A; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G; McCaw, James M; Bloom, Jesse D; Hurt, Aeron C

    2014-04-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide.

  10. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1pdm09 influenza viruses.

    Directory of Open Access Journals (Sweden)

    Jeff Butler

    2014-04-01

    Full Text Available Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1 influenza virus (A(H1N1pdm09, the proportion of A(H1N1pdm09 viruses that are oseltamivir resistant (OR has generally been low. However, a cluster of OR A(H1N1pdm09 viruses, encoding the neuraminidase (NA H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1pdm09 viruses. Our findings suggest that recent A(H1N1pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1pdm09 viruses, increasing the risk that OR A(H1N1pdm09 will emerge and spread worldwide.

  11. Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses

    Science.gov (United States)

    Butler, Jeff; Hooper, Kathryn A.; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G.; McCaw, James M.; Bloom, Jesse D.; Hurt, Aeron C.

    2014-01-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide. PMID:24699865

  12. Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico.

    Directory of Open Access Journals (Sweden)

    Gerardo Chowell

    2011-05-01

    Full Text Available BACKGROUND: Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April-December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. METHODS AND FINDINGS: We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April-December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenz