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

PubMed

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

2017-02-14

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

2016-06-01

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

Testing Update on 20 and 25-Ah Lithium Ion Cells

NASA Technical Reports Server (NTRS)

Bruce, Gregg C.; Mardikian, Pamella; Edwards, Sherri; Bugga, Kumar; Chin, Keith; Smart, Marshall; Surampudi, Subbarao

2003-01-01

Eagle-Picher Energy Products has worked on lithium ion batteries for approximately 8 years. During that period EPEPC developed and delivered several cell sizes on a program funded by the USAF and Canadian DND. Designs are wound cylindrical cells from 7 to 40-Ah. Most cells delivered were approximately 25-Ah due to requirements of Mars missions. Several iterations of cells were manufactured and delivered for evaluation. The first design was 20-Ah, Design I, and the second was a 25-Ah, Design II.

Aa Ah Nak

ERIC Educational Resources Information Center

Tha, Na Gya; Wus, Thay

2017-01-01

In this article, Aa Ah Nak, the authors' methodology presents not only various reflections but also diverse contradictions about the Aa Nii language as well as language revitalization. This article explores language foundation and how the Aa Nii language revitalization is inextricably linked to the genocide and resulting historic trauma pervasive…

Interaction of Diuron and Related Substituted Phenylureas with the Ah Receptor Pathway

PubMed Central

Zhao, Bin; Baston, David S.; Hammock, Bruce; Denison, Michael S.

2011-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals, including the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin. Here, we have examined the ability of diuron, a widely used herbicide, and several structurally related substituted phenylureas to bind to and activate/inhibit the AhR and AhR signal transduction. Diuron induced CYP1A1 mRNA levels in mouse hepatoma (Hepa1c1c7) cells and AhR-dependent luciferase reporter gene expression in stably transfected mouse, rat, guinea pig, and human cell lines. In addition, ligand binding and gel retardation analysis demonstrated the ability of diuron to competitively bind to and stimulate AhR transformation and DNA binding in vitro and in intact cells. Several structurally related substituted phenylureas competitively bound to the guinea pig hepatic cytosolic AhR, inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced AhR-dependent luciferase reporter gene expression in a species-specific manner and stimulated AhR transformation and DNA binding, consistent with their role as partial AhR agonists. These results demonstrate not only that diuron and related substituted phenylureas are AhR ligands but also that exposure to these chemicals could induce/inhibit AhR-dependent biological effects. PMID:16788953

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

PubMed

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.

A Historical Perspective of Influenza A(H1N2) Virus

PubMed Central

McVernon, Jodie; Hall, Robert; Leder, Karin

2014-01-01

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals. PMID:24377419

A historical perspective of influenza A(H1N2) virus.

PubMed

Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

2014-01-01

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

AhR transcriptional activity in serum of Inuits across Greenlandic districts

PubMed Central

Long, Manhai; Deutch, Bente; Bonefeld-Jorgensen, Eva C

2007-01-01

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 POP mixture was the

The Aryl Hydrocarbon Receptor (AhR) as a Drug Target for Cancer Chemotherapy.

PubMed

Safe, Stephen; Cheng, Yating; Jin, Un-Ho

2017-02-01

The aryl hydrocarbon receptor (AhR) is overexpressed in some patients with different tumor types, and the receptor can be a negative or positive prognostic factor. There is also evidence from both in vivo and in vitro cell culture models that the AhR can exhibit tumor-specific pro-oncogenic and tumor suppressor-like functions and therefore can be treated with AhR antagonists or agonists, respectively. Successful clinical applications of AhR ligands will require the synthesis and development of selective AhR modulators (SAhRMs) with tumor-specific AhR agonist or antagonist activity, and some currently available compounds such as indole-3-carbinol and diindolylmethane-(DIM) and synthetic AhR antagonists are potential drug candidates. There is also evidence that some AhR-active pharmaceuticals, including tranilast, flutamide, hydroxytamoxifen and omeprazole or their derivatives, may be effective AhR-dependent anticancer agents for single or combination cancer chemotherapies for treatment of breast and pancreatic cancers.

Fatal intoxications associated with the designer opioid AH-7921.

PubMed

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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aryl Hydrocarbon Receptor (AhR) Deletion in Cerebellar Granule Neuron Precursors Impairs Neurogenesis

PubMed Central

Dever, Daniel P.; Adham, Zachariah O.; Thompson, Bryan; Genestine, Matthieu; Cherry, Jonathan; Olschowka, John A.; DiCicco-Bloom, Emanuel; Opanashuk, Lisa A.

2015-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated member of the basic-helix-loop-helix (bHLH)/PER-ARNT-SIM(PAS) transcription factor superfamily that also mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence suggests that AhR influences the development of many tissues, including the central nervous system. Our previous studies suggest that sustained AhR activation by TCDD and/or AhR deletion disrupts cerebellar granule neuron precursor (GNP) development. In the current study, to determine whether endogenous AhR controls GNP development in a cell autonomous manner, we created a GNP-specific AhR deletion mouse, AhRfx/fx/Math1CRE/+ (AhR CKO). Selective AhR deletion in GNPs produced abnormalities in proliferation and differentiation. Specifically, fewer GNPs were engaged in S-phase, as demonstrated by ~25% reductions in thymidine (in vitro) and BrdU (in vivo) incorporation. Furthermore, total granule neuron numbers in the IGL at PND21 and PND60 were diminished in AhR CKO mice compared to controls. On the other hand, differentiation was enhanced, including ~40% increase in neurite outgrowth and 50% increase in GABARα6 receptor expression in deletion mutants. Our results suggest that AhR activity plays a role in regulating granule neuron number and differentiation, possibly by coordinating this GNP developmental transition. These studies provide novel insights for understanding the normal roles of AhR signaling during cerebellar granule cell neurogenesis, and may have important implications for the effects of environmental factors in cerebellar dysgenesis. PMID:26243376

The regulation mechanisms of AhR by molecular chaperone complex.

PubMed

Kudo, Ikuru; Hosaka, Miki; Haga, Asami; Tsuji, Noriko; Nagata, Yuhtaroh; Okada, Hirotaka; Fukuda, Kana; Kakizaki, Yuka; Okamoto, Tomoya; Grave, Ewa; Itoh, Hideaki

2018-03-01

The AhR, so called the dioxin receptor, is a member of the nuclear receptor superfamily. The ligand-free AhR forms a cytosolic protein complex with the molecular chaperone HSP90, co-chaperone p23, and XAP2 in the cytoplasm. Following ligand binding like 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the AhR translocates into the nucleus. Although it has been reported that HSP90 regulates the translocation of the AhR to the nucleus, the precise activation mechanisms of the AhR have not yet been fully understood. AhR consists of the N-terminal bHLH domain containing NLS and NES, the middle PAS domain and the C-terminal transactivation domain. The PAS domain is familiar as a ligand and HSP90 binding domain. In this study, we focused on the bHLH domain that was thought to be a HSP90 binding domain. We investigated the binding properties of bHLH to HSP90. We analyzed the direct interaction of bHLH with HSP90, p23 and XAP2 using purified proteins. We found that not only the PAS domain but also the bHLH domain bound to HSP90. The bHLH domain forms complex with HSP90, p23 and XAP2. We also determined the bHLH binding domain was HSP90 N-domain. The bHLH domain makes a complex with HSP90, p23 and XAP2 via the HSP90 N-domain. Although the NLS is closed in the absence of a ligand, the structure of AhR will be changed in the presence of a ligand, which leads to NLS open, result in the nuclear translocation of AhR.

Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

PubMed Central

Havers, Fiona; Iuliano, A. Danielle; Davis, C. Todd; Sar, Borann; Sovann, Ly; Chin, Savuth; Corwin, Andrew L.; Vongphrachanh, Phengta; Douangngeun, Bounlom; Lindblade, Kim A.; Chittaganpitch, Malinee; Kaewthong, Viriya; Kile, James C.; Nguyen, Hien T.; Pham, Dong V.; Donis, Ruben O.; Widdowson, Marc-Alain

2015-01-01

During February 2013–March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013–May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely. PMID:25897654

Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast

PubMed Central

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

2015-01-01

Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on L-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assays in recombinant cell lines derived from four different species, although significant species differences in relative potency was observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. Malassezia furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.1 PMID:25721496

Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism.

PubMed

Korecka, Agata; Dona, Anthony; Lahiri, Shawon; Tett, Adrian James; Al-Asmakh, Maha; Braniste, Viorica; D'Arienzo, Rossana; Abbaspour, Afrouz; Reichardt, Nicole; Fujii-Kuriyama, Yoshiaki; Rafter, Joseph; Narbad, Arjan; Holmes, Elaine; Nicholson, Jeremy; Arulampalam, Velmurugesan; Pettersson, Sven

2016-01-01

The ligand-induced transcription factor, aryl hydrocarbon receptor (AhR) is known for its capacity to tune adaptive immunity and xenobiotic metabolism-biological properties subject to regulation by the indigenous microbiome. The objective of this study was to probe the postulated microbiome-AhR crosstalk and whether such an axis could influence metabolic homeostasis of the host. Utilising a systems-biology approach combining in-depth 1 H-NMR-based metabonomics (plasma, liver and skeletal muscle) with microbiome profiling (small intestine, colon and faeces) of AhR knockout (AhR -/- ) and wild-type (AhR +/+ ) mice, we assessed AhR function in host metabolism. Microbiome metabolites such as short-chain fatty acids were found to regulate AhR and its target genes in liver and intestine. The AhR signalling pathway, in turn, was able to influence microbiome composition in the small intestine as evident from microbiota profiling of the AhR +/+ and AhR -/- mice fed with diet enriched with a specific AhR ligand or diet depleted of any known AhR ligands. The AhR -/- mice also displayed increased levels of corticosterol and alanine in serum. In addition, activation of gluconeogenic genes in the AhR -/- mice was indicative of on-going metabolic stress. Reduced levels of ketone bodies and reduced expression of genes involved in fatty acid metabolism in the liver further underscored this observation. Interestingly, exposing AhR -/- mice to a high-fat diet showed resilience to glucose intolerance. Our data suggest the existence of a bidirectional AhR-microbiome axis, which influences host metabolic pathways.

AhR-deficiency as a cause of demyelinating disease and inflammation.

PubMed

Juricek, Ludmila; Carcaud, Julie; Pelhaitre, Alice; Riday, Thorfinn T; Chevallier, Aline; Lanzini, Justine; Auzeil, Nicolas; Laprévote, Olivier; Dumont, Florent; Jacques, Sebastien; Letourneur, Frank; Massaad, Charbel; Agulhon, Cendra; Barouki, Robert; Beraneck, Mathieu; Coumoul, Xavier

2017-08-29

The Aryl hydrocarbon Receptor(AhR) is among the most important receptors which bind pollutants; however it also regulates signaling pathways independently of such exposure. We previously demonstrated that AhR is expressed during development of the central nervous system(CNS) and that its deletion leads to the occurrence of a congenital nystagmus. Objectives of the present study are to decipher the origin of these deficits, and to identify the role of the AhR in the development of the CNS. We show that the AhR-knockout phenotype develops during early infancy together with deficits in visual-information-processing which are associated with an altered optic nerve myelin sheath, which exhibits modifications in its lipid composition and in the expression of myelin-associated-glycoprotein(MAG), a cell adhesion molecule involved in myelin-maintenance and glia-axon interaction. In addition, we show that the expression of pro-inflammatory cytokines is increased in the impaired optic nerve and confirm that inflammation is causally related with an AhR-dependent decreased expression of MAG. Overall, our findings demonstrate the role of the AhR as a physiological regulator of myelination and inflammatory processes in the developing CNS. It identifies a mechanism by which environmental pollutants might influence CNS myelination and suggest AhR as a relevant drug target for demyelinating diseases.

Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism

PubMed Central

Korecka, Agata; Dona, Anthony; Lahiri, Shawon; Tett, Adrian James; Al-Asmakh, Maha; Braniste, Viorica; D’Arienzo, Rossana; Abbaspour, Afrouz; Reichardt, Nicole; Fujii-Kuriyama, Yoshiaki; Rafter, Joseph; Narbad, Arjan; Holmes, Elaine; Nicholson, Jeremy; Arulampalam, Velmurugesan; Pettersson, Sven

2016-01-01

The ligand-induced transcription factor, aryl hydrocarbon receptor (AhR) is known for its capacity to tune adaptive immunity and xenobiotic metabolism—biological properties subject to regulation by the indigenous microbiome. The objective of this study was to probe the postulated microbiome-AhR crosstalk and whether such an axis could influence metabolic homeostasis of the host. Utilising a systems-biology approach combining in-depth 1H-NMR-based metabonomics (plasma, liver and skeletal muscle) with microbiome profiling (small intestine, colon and faeces) of AhR knockout (AhR−/−) and wild-type (AhR+/+) mice, we assessed AhR function in host metabolism. Microbiome metabolites such as short-chain fatty acids were found to regulate AhR and its target genes in liver and intestine. The AhR signalling pathway, in turn, was able to influence microbiome composition in the small intestine as evident from microbiota profiling of the AhR+/+ and AhR−/− mice fed with diet enriched with a specific AhR ligand or diet depleted of any known AhR ligands. The AhR−/− mice also displayed increased levels of corticosterol and alanine in serum. In addition, activation of gluconeogenic genes in the AhR−/− mice was indicative of on-going metabolic stress. Reduced levels of ketone bodies and reduced expression of genes involved in fatty acid metabolism in the liver further underscored this observation. Interestingly, exposing AhR−/− mice to a high-fat diet showed resilience to glucose intolerance. Our data suggest the existence of a bidirectional AhR-microbiome axis, which influences host metabolic pathways. PMID:28721249

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

PubMed

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. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway.

PubMed

Pombo, Mónica; Lamé, Michael W; Walker, Naomi J; Huynh, Danh H; Tablin, Fern

2015-05-19

The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

PubMed

Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

PubMed

Petrie, Joshua G; Parkhouse, Kaela; Ohmit, Suzanne E; Malosh, Ryan E; Monto, Arnold S; Hensley, Scott E

2016-12-15

During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.

PubMed

Manzella, Christopher; Singhal, Megha; Alrefai, Waddah A; Saksena, Seema; Dudeja, Pradeep K; Gill, Ravinder K

2018-04-17

Aryl hydrocarbon receptor (AhR) is a nuclear receptor that controls xenobiotic detoxification via induction of cytochrome P450 1A1 (CYP1A1) and regulates immune responses in the intestine. Metabolites of L-tryptophan activate AhR, which confers protection against intestinal inflammation. We tested the hypothesis that serotonin (5-HT) is an endogenous activator of AhR in intestinal epithelial cells. Treatment of Caco-2 monolayers with 5-HT induced CYP1A1 mRNA in a time- and concentration-dependent manner and also stimulated CYP1A1 activity. CYP1A1 induction by 5-HT was dependent upon uptake via serotonin transporter (SERT). Antagonism of AhR and knockdown of AhR and its binding partner aryl hydrocarbon receptor nuclear translocator (ARNT) attenuated CYP1A1 induction by 5-HT. Activation of AhR was evident by its nuclear translocation after 5-HT treatment and by induction of an AhR-responsive luciferase reporter. In vivo studies showed a dramatic decrease in CYP1A1 expression and other AhR target genes in SERT KO ileal mucosa by microarray analysis. These results suggest that intracellular accumulation of 5-HT via SERT induces CYP1A1 expression via AhR in intestinal epithelial cells, and SERT deficiency in vivo impairs activation of AhR. Our studies provide a novel link between the serotonergic and AhR pathways which has implications in xenobiotic metabolism and intestinal inflammation.

Lethal poisonings with AH-7921 in combination with other substances.

PubMed

Karinen, Ritva; Tuv, Silja Skogstad; Rogde, Sidsel; Peres, Mariana Dadalto; Johansen, Unni; Frost, Joachim; Vindenes, Vigdis; Øiestad, Åse Marit Leere

2014-11-01

AH-7921 is a synthetic μ-opioid agonist, approximately equipotent with morphine. We report the death of two young individuals after ingestion of AH-7921 in combination with other psychoactive drugs. In the first case a young man died shortly after ingesting Internet drugs. Toxicological analysis of post mortem peripheral blood revealed AH-7921 (0.43 mg/L), 2-FMA (0.0069 mg/L) and 3-MMC (0.0021 mg/L) as well as codeine (0.42 mg/L), codeine-6-glucuronide (0.77 mg/L) and acetaminophen (18.7 mg/L). The second case involved a young female found dead at home. The only positive finding at medicolegal autopsy was needle marks. Toxicological analysis revealed AH-7921 (0.33 mg/L), methoxetamine (MXE) (0.064 mg/L), etizolam (0.27 mg/L), phenazepam (1.33 mg/L), 7-aminonitrazepam (0.043 mg/L), diazepam (0.046 mg/L), nordiazepam (0.073 mg/L), and oxazepam (0.018 mg/L) in blood. In both cases intoxication with AH-7921 in combination with other psychoactive drugs was considered to be the cause of death. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells.

PubMed

Jang, Hyo Sang; Pearce, Martin; O'Donnell, Edmond F; Nguyen, Bach Duc; Truong, Lisa; Mueller, Monica J; Bisson, William H; Kerkvliet, Nancy I; Tanguay, Robert L; Kolluri, Siva Kumar

2017-12-01

We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure-activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells. Suppression of AhR expression strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos revealed that Y134 has a significantly better safety profile than raloxifene. Our studies also identified an analog of raloxifene that acts as a partial antagonist of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional activity. We conclude that Y134 is a promising raloxifene analog for further optimization as an anti-cancer agent targeting the AhR.

Development and fabrication of large vented nickel--zinc cells. Final report. [300 Ah

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

Donnel, C.P.I.

1975-12-01

A preliminary cell design for a 300-Ah vented nickel--zinc cell was established based on volume requirements and cell component materials selected by NASA Lewis Research Center. A 100-Ah cell configuration was derived from the 300-Ah cell design utilizing the same size electrodes, separators, and cell terminal hardware. The first cells fabricated were four groups of three cells each in the 100-Ah size. These 100-Ah experimental nickel--zinc cells had as common components the nickel positive electrodes (GFM), flexible inorganic separator (GFM) bags on the negative electrodes, pressed powder zinc oxide electrodes, and cell containers with hardware. The variations introduced were fourmore » differing electrolyte absorber (interseparator) systems used to encase the nickel positive electrodes of each cell group. The four groups of 100-Ah experimental vented nickel--zinc cells were tested to determine, based on cell performance, the best two interseparator systems. Using the two interseparator systems, two groups of experimental 300-AH cells were fabricated. Each group of three cells differed only in the interseparator material used. The six cells were filled, formed and tested to evaluate the interseparator materials and investigate the performance characteristics of the 300-Ah cell configuration and its components. (auth)« less

Activation of AhR-mediated toxicity pathway by emerging ...

EPA Pesticide Factsheets

Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-luc transactivation assay, with 13/18 causing concentration-dependent AhR activation. Potencies of several congeners were similar to those of mono-ortho substituted polychlorinated biphenyls. A RNA sequencing (RNA-seq)-based transcriptomic analysis was performed on H4IIE cells treated with two PCDPS congeners, 2,2',3,3',4,5,6-hepta-CDPS, and 2,4,4',5-tetra-CDPS. Results of RNA-seq revealed a remarkable modulation on a relatively short gene list by exposure to the tested concentrations of PCDPSs, among which, Cyp1 responded with the greatest fold up-regulation. Both the identities of the modulated transcripts and the associated pathways were consistent with targets and pathways known to be modulated by other types of AhR agonists and there was little evidence for significant off-target effects within the cellular context of the H4IIE bioassay. The results suggest AhR activation as a toxicologically relevant mode of action for PCDPSs suggests the utility of AhR-related toxicity pathways for predicting potential hazards associated with PCDPS exposure in mammals and potentially other vertebrates. Polychlorinated diphenyl sulfides (PCDPSs) are a group of en

Genesis of Influenza A(H5N8) Viruses

PubMed Central

El-Shesheny, Rabeh; Barman, Subrata; Feeroz, Mohammed M.; Hasan, M. Kamrul; Jones-Engel, Lisa; Franks, John; Turner, Jasmine; Seiler, Patrick; Walker, David; Friedman, Kimberly; Kercher, Lisa; Begum, Sajeda; Akhtar, Sharmin; Datta, Ashis Kumar; Krauss, Scott; Kayali, Ghazi; McKenzie, Pamela; Webby, Richard J.

2017-01-01

Highly pathogenic avian influenza A(H5N8) clade 2.3.4.4 virus emerged in 2016 and spread to Russia, Europe, and Africa. Our analysis of viruses from domestic ducks at Tanguar haor, Bangladesh, showed genetic similarities with other viruses from wild birds in central Asia, suggesting their potential role in the genesis of A(H5N8). PMID:28609260

Genesis of Influenza A(H5N8) Viruses.

PubMed

El-Shesheny, Rabeh; Barman, Subrata; Feeroz, Mohammed M; Hasan, M Kamrul; Jones-Engel, Lisa; Franks, John; Turner, Jasmine; Seiler, Patrick; Walker, David; Friedman, Kimberly; Kercher, Lisa; Begum, Sajeda; Akhtar, Sharmin; Datta, Ashis Kumar; Krauss, Scott; Kayali, Ghazi; McKenzie, Pamela; Webby, Richard J; Webster, Robert G

2017-08-01

Highly pathogenic avian influenza A(H5N8) clade 2.3.4.4 virus emerged in 2016 and spread to Russia, Europe, and Africa. Our analysis of viruses from domestic ducks at Tanguar haor, Bangladesh, showed genetic similarities with other viruses from wild birds in central Asia, suggesting their potential role in the genesis of A(H5N8).

Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders

PubMed Central

Busbee, Philip B; Rouse, Michael; Nagarkatti, Mitzi; Nagarkatti, Prakash S

2014-01-01

The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3+ regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells. Such findings have opened new avenues of research on the possibility of targeting the AhR to treat inflammatory and autoimmune diseases. Specifically, this review will discuss the current research involving natural and dietary AhR ligands. In addition, evidence indicating the potential use of these ligands in regulating inflammation in various diseases will be highlighted. The importance of the AhR in immunological processes can be illustrated by expression of this receptor on a majority of immune cell types. In addition, AhR signaling pathways have been reported to influence a number of genes responsible for mediating inflammation and other immune responses. As interest in the AhR and its ligands increases, it seems prudent to consolidate current research on the contributions of these ligands to immune regulation during the course of inflammatory diseases. PMID:23731446

Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation.

PubMed

Ito, Shunsuke; Osaka, Mizuko; Edamatsu, Takeo; Itoh, Yoshiharu; Yoshida, Masayuki

2016-08-01

The aryl hydrocarbon receptor (AhR), a ligand-inducible transcription factor mediating toxic effects of dioxins and uremic toxins, has recently emerged as a pathophysiological regulator of immune-inflammatory conditions. Indoxyl sulfate, a uremic toxin, is associated with cardiovascular disease in patients with chronic kidney disease and has been shown to be a ligand for AhR. The aim of this study was to investigate the potential role of AhR in indoxyl sulfate-induced leukocyte-endothelial interactions. Endothelial cell-specific AhR knockout (eAhR KO) mice were produced by crossing AhR floxed mice with Tie2 Cre mice. Indoxyl sulfate was administered for 2 weeks, followed by injection of TNF-α. Leukocyte recruitment to the femoral artery was assessed by intravital microscopy. Vascular endothelial cells were transfected with siRNA specific to AhR (siAhR) and treated with indoxyl sulfate, followed by stimulation with TNF-α. Indoxyl sulfate dramatically enhanced TNF-α-induced leukocyte recruitment to the vascular wall in control animals but not in eAhR KO mice. In endothelial cells, siAhR significantly reduced indoxyl sulfate-enhanced leukocyte adhesion as well as E-selectin expression, whereas the activation of JNK and nuclear factor-κB was not affected. A luciferase assay revealed that the region between －153 and －146 bps in the E-selectin promoter was responsible for indoxyl sulfate activity via AhR. Mutational analysis of this region revealed that activator protein-1 (AP-1) is responsible for indoxyl sulfate-triggered E-selectin expression via AhR. AhR mediates indoxyl sulfate-enhanced leukocyte-endothelial interactions through AP-1 transcriptional activity, which may constitute a new mechanism of vascular inflammation in patients with renal disease.

A(H1N1)pdm09 influenza infection: vaccine inefficiency.

PubMed

Friedman, Nehemya; Drori, Yaron; Pando, Rakefet; Glatman-Freedman, Aharona; Sefty, Hanna; Bassal, Ravit; Stein, Yaniv; Shohat, Tamy; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

2017-05-16

The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015-2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

Simultaneous inhibition of aryl hydrocarbon receptor (AhR) and Src abolishes androgen receptor signaling.

PubMed

Ghotbaddini, Maryam; Cisse, Keyana; Carey, Alexis; Powell, Joann B

2017-01-01

Altered c-Src activity has been strongly implicated in the development, growth, progression, and metastasis of human cancers including prostate cancer. Src is known to regulate several biological functions of tumor cells, including proliferation. There are several Src inhibitors under evaluation for clinical effectiveness but have shown little activity in monotherapy trials of solid tumors. Combination studies are being explored by in vitro analysis and in clinical trials. Here we investigate the effect of simultaneous inhibition of the aryl hydrocarbon receptor (AhR) and Src on androgen receptor (AR) signaling in prostate cancer cells. AhR has also been reported to interact with the Src signaling pathway during prostate development. c-Src protein kinase is associated with the AhR complex in the cytosol and upon ligand binding to AhR, c-Src is activated and released from the complex. AhR has also been shown to regulate AR signaling which remains functionally important in the development and progression of prostate cancer. We provide evidence that co-inhibition of AhR and Src abolish AR activity. Evaluation of total protein and cellular fractions revealed decreased pAR expression and AR nuclear localization. Assays utilizing an androgen responsive element (ARE) and qRT-PCR analysis of AR genes revealed decreased AR promoter activity and transcriptional activity in the presence of both AhR and Src inhibitors. Furthermore, co-inhibition of AhR and Src reduced the growth of prostate cancer cells compared to individual treatments. Several studies have revealed that AhR and Src individually inhibit cellular proliferation. However, this study is the first to suggest simultaneous inhibition of AhR and Src to inhibit AR signaling and prostate cancer cell growth.

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

PubMed

Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

2017-01-01

Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

Aryl hydrocarbon receptor (AhR) a possible target for the treatment of skin disease.

PubMed

Napolitano, Maddalena; Patruno, Cataldo

2018-07-01

Aryl hydrocarbon receptor (AhR) is a transcription factor expressed in all skin cells type. It responds to exogenous and endogenous chemicals by inducing/repressing the expression of several genes with toxic or protective effects in a wide range of species and tissues. In healthy skin, AhR signalling contributes to keratinocytes differentiation, skin barrier function, skin pigmentation, and mediates oxidative stress. In the last years, some studies have shown that AhR seems to be involved in the pathogenesis of some skin diseases, even if the currently available data are contradictory. Indeed, while the blocking the AhR signalling activity could prevent or treat skin cancer, the AhR activation seems to be advantageous for the treatment of inflammatory skin diseases. Therefore, for its multifaceted role in skin diseases, AhR seems to be an attractive therapeutic target. Indeed, recently some molecules have been identified for the prevention of skin cancer and the treatment of inflammatory skin diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in breast cancer cells.

PubMed

Bekki, Kanae; Vogel, Helena; Li, Wen; Ito, Tomohiro; Sweeney, Colleen; Haarmann-Stemmann, Thomas; Matsumura, Fumio; Vogel, Christoph F A

2015-05-01

The aryl hydrocarbon receptor (AhR) is well known as a ligand binding transcription factor regulating various biological effects. Previously we have shown that long-term exposure to estrogen in breast cancer cells caused not only down regulation of estrogen receptor (ER) but also overexpression of AhR. The AhR interacts with several cell signaling pathways associated with induction of tyrosine kinases, cytokines and growth factors which may support the survival roles of AhR escaping from apoptosis elicited by a variety of apoptosis inducing agents in breast cancer. In this study, we studied the anti-apoptotic role of AhR in different breast cancer cells when apoptosis was induced by exposure to UV light and chemotherapeutic agents. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in AhR overexpressing breast cancer cells effectively suppressed the apoptotic response induced by UV-irradiation, doxorubicin, lapatinib and paclitaxel. The anti-apoptotic response of TCDD was uniformly antagonized by the treatment with 3'methoxy-4'nitroflavone (MNF), a specific antagonist of AhR. TCDD's survival action of apoptosis was accompanied with the induction of well-known inflammatory genes, such as cyclooxygenase-2 (COX-2) and NF-κB subunit RelB. Moreover, TCDD increased the activity of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO), which metabolizes tryptophan to kynurenine (Kyn) and mediates tumor immunity. Kyn also acts as an AhR ligand like TCDD, and kyn induced an anti-apoptotic response in breast cancer cells. Accordingly, our present study suggests that AhR plays a pivotal role in the development of breast cancer via the suppression of apoptosis, and provides an idea that the use of AhR antagonists with chemotherapeutic agents may effectively synergize the elimination of breast cancer cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional and phenotypic effects of AhR activation in inflammatory dendritic cells

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

Bankoti, Jaishree; Center for Environmental Health Sciences, University of Montana, Missoula, MT; Rase, Ben

2010-07-15

Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immune suppression. Dendritic cells (DCs) are key antigen presenting cells governing T cell activation and differentiation. However, the consequences of AhR activation in DCs are not fully defined. We hypothesized that AhR activation alters DC differentiation and generates dysfunctional DCs. To test this hypothesis, inflammatory bone marrow-derived DCs (BMDCs) from C57Bl/6 mice were generated in the presence of vehicle or TCDD. TCDD decreased CD11c expression but increased MHC class II, CD86 and CD25 expression on the BMDCs. The effects of TCDD were strictly AhR-dependent but not exclusively DRE-mediated. Similar effects weremore » observed with two natural AhR ligands, 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid (ITE). TCDD increased LPS- and CpG-induced IL-6 and TNF-{alpha} production by BMDCs but decreased their NO production. TCDD decreased CpG-induced IL-12p70 production by BMDCs but did not affect their secretion of IL-10. TCDD downregulated LPS- and CpG-induced NF-kB p65 levels and induced a trend towards upregulation of RelB levels in the BMDCs. AhR activation by TCDD modulated BMDC uptake of both soluble and particulate antigens. Induction of indoleamine-2,3-dioxygenase (IDO) and TGF-{beta}3 has been implicated in the generation of regulatory T cells following AhR activation. TCDD increased IDO1, IDO2 and TGF-{beta}3 mRNA levels in BMDCs as compared to vehicle. Despite the induction of regulatory mediators, TCDD-treated BMDCs failed to suppress antigen-specific T cell activation. Thus, AhR activation can directly alter the differentiation and innate functions of inflammatory DCs without affecting their ability to successfully interact with T cells.« less

AhR mediates an anti-inflammatory feedback mechanism in human Langerhans cells involving FcεRI and IDO.

PubMed

Koch, S; Stroisch, T J; Vorac, J; Herrmann, N; Leib, N; Schnautz, S; Kirins, H; Förster, I; Weighardt, H; Bieber, T

2017-11-01

Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of patients with atopic dermatitis (AD) carry the high-affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. We investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro-generated LC. Epidermal cells from healthy skin were analyzed for their expression of AhR and AhRR. LC generated from CD34 + hematopoietic stem cells (CD34LC) were treated with the UV photoproduct and AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). Cell surface receptors, transcription factors, and the tolerogenic tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) were analyzed using flow cytometry and quantitative PCR. Epidermal LC and CD34LC express AhR and AhRR. AhR was also found in keratinocytes, which lack AhRR. AhR activation of LC by FICZ caused downregulation of FcεRI in CD34LC without affecting their maturation. AhR-mediated regulation of FcεRI did not involve any known transcription factors related to this receptor. Furthermore, we could show upregulation of IDO mediated by AhR engagement. Our study shows that AhR activation by FICZ reduces FcεRI and upregulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain

PubMed Central

Castilla, Jesús; Pozo, Francisco

2017-01-01

Background Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. PMID:28614376

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).

PubMed

Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K; Donnell, Joan M O; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco

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. Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. Copyright © 2015 The Authors

Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9).

PubMed

Dudley, Joseph P; Mackay, Ian M

2013-11-01

We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations. Copyright © 2013 Elsevier B.V. All rights reserved.

Biological Role of Trichoderma harzianum-Derived Platelet-Activating Factor Acetylhydrolase (PAF-AH) on Stress Response and Antagonism

PubMed Central

Yu, Chuanjin; Fan, Lili; Wu, Qiong; Fu, Kehe; Gao, Shigang; Wang, Meng; Gao, Jinxin; Li, Yaqian; Chen, Jie

2014-01-01

We investigated the properties of platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum. The enzyme, comprised of 572 amino acids, shares high homology with PAF-AH proteins from T. koningii and other microbial species. The optimum enzymatic activity of PAF-AH occurred at pH 6 in the absence of Ca2+ and it localized in the cytoplasm, and we observed the upregulation of PAF-AH expression in response to carbon starvation and strong heat shock. Furthermore, PAF-AH knockout transformant growth occurred more slowly than wild type cells and over-expression strains grown in SM medium at 37°C and 42°C. In addition, PAF-AH expression significantly increased under a series of maize root induction assay. Eicosanoic acid and ergosterol levels decreased in the PAF-AH knockouts compared to wild type cells, as revealed by GC/MS analysis. We also determined stress responses mediated by PAF-AH were related to proteins HEX1, Cu/Zn superoxide dismutase, and cytochrome c. Finally, PAF-AH exhibited antagonistic activity against Rhizoctonia solani in plate confrontation assays. Our results indicate PAF-AH may play an important role in T. harzianum stress response and antagonism under diverse environmental conditions. PMID:24964161

Biological role of Trichoderma harzianum-derived platelet-activating factor acetylhydrolase (PAF-AH) on stress response and antagonism.

PubMed

Yu, Chuanjin; Fan, Lili; Wu, Qiong; Fu, Kehe; Gao, Shigang; Wang, Meng; Gao, Jinxin; Li, Yaqian; Chen, Jie

2014-01-01

We investigated the properties of platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum. The enzyme, comprised of 572 amino acids, shares high homology with PAF-AH proteins from T. koningii and other microbial species. The optimum enzymatic activity of PAF-AH occurred at pH 6 in the absence of Ca2+ and it localized in the cytoplasm, and we observed the upregulation of PAF-AH expression in response to carbon starvation and strong heat shock. Furthermore, PAF-AH knockout transformant growth occurred more slowly than wild type cells and over-expression strains grown in SM medium at 37°C and 42°C. In addition, PAF-AH expression significantly increased under a series of maize root induction assay. Eicosanoic acid and ergosterol levels decreased in the PAF-AH knockouts compared to wild type cells, as revealed by GC/MS analysis. We also determined stress responses mediated by PAF-AH were related to proteins HEX1, Cu/Zn superoxide dismutase, and cytochrome c. Finally, PAF-AH exhibited antagonistic activity against Rhizoctonia solani in plate confrontation assays. Our results indicate PAF-AH may play an important role in T. harzianum stress response and antagonism under diverse environmental conditions.

Design and Performance Data for 81 Ah FNC Cells

NASA Technical Reports Server (NTRS)

Cohen, F.; Anderman, Menahem

1997-01-01

Design and performance data for 81 Ah FNC cells are given. The conclusions are: that a sealed Ni-Cd cells are not limited to 50 Ah with the FNC design; energy densities of 40 Wh/kg in a conservative high Cd, high electrolyte design have been demonstrated; uniform ATP data and LEO cycling performance is being demonstrated; internal cell pressures remain low under all conditions; and no conditioning is necessary under any LEO profile; accelerated LEO cycling exhibits performance well beyond traditional space Ni-Cd cells.

Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH) administration.

PubMed

Teixeira-da-Cunha, Mariana G A; Gomes, Rachel N; Roehrs, Nathassia; Bozza, Fernando A; Prescott, Stephen M; Stafforini, Diana; Zimmerman, Guy A; Bozza, Patricia T; Castro-Faria-Neto, Hugo C

2013-01-01

Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model.

Dysregulation of Notch and ERα signaling in AhR−/− male mice

PubMed Central

Huang, Bo; Butler, Ryan; Miao, Yifei; Dai, Yubing; Wu, Wanfu; Su, Wen; Fujii-Kuriyama, Yoshiaki; Warner, Margaret; Gustafsson, Jan-Åke

2016-01-01

The aryl hydrocarbon receptor (AhR) is now recognized as an important physiological regulator in the immune and reproductive systems, and in the development of the liver and vascular system. AhR regulates cell cycle, cell proliferation, and differentiation through interacting with other signaling pathways, like estrogen receptor α (ERα), androgen receptor (AR), and Notch signaling. In the present study, we investigated Notch and estrogen signaling in AhR−/− mice. We found low fertility with degenerative changes in the testes, germ cell apoptosis, and a reduced number of early spermatids. There was no change in aromatase, AR, ERα, or ERβ expression in the testis and no detectable change in serum estrogen levels. However, expression of Notch receptors (Notch1 and Notch3) and their target Hairy and Enhancer of Split homolog 1 (HES1) was reduced. In addition, the testosterone level was slightly reduced in the serum. In the mammary fat pad, AhR appeared to regulate estrogen signaling because, in AhR−/− males, there was significant growth of the mammary ducts with high expression of ERα in the ductal epithelium. The enhanced mammary ductal growth appears to be related to overexpression of ERα accompanied by a high proliferation index, whereas the reduced fertility appears to be related defects in Notch signaling that leads to reduced expression of HES1 and, consequently, early maturation of spermatocytes and a depletion of primary spermatids. Previous reports have indicated that AhR pathway is associated with infertility in men. Our results provide a mechanistic explanation for this defect. PMID:27688768

Modifications to Optimize the AH-1Z Human Machine Interface

DTIC Science & Technology

2013-04-18

accomplish this, a complete workload study of tasks performed by aircrew in the AH-1Z must be completed in the near future in order to understand...design flaws and guide future design and integration of increased capability. Additionally, employment of material solutions to provide aircrew with the...accomplish this, a complete workload study of tasks performed by aircrew in the AH-1Z must be completed in the near future in order to understand

Normal mast cell numbers in the tissues of AhR-deficient mice.

PubMed

Pilz, Caroline; Feyerabend, Thorsten; Sonner, Jana; Redaelli, Chiara; Peter, Katharina; Kunze, Anja; Haas, Katharina; Esser, Charlotte; Schäkel, Knut; Wick, Wolfgang; Rodewald, Hans-Reimer; Lanz, Tobias V; Platten, Michael

2016-01-01

The transcription factor aryl hydrocarbon receptor (AhR) acts as an immunomodulatory molecule in several immune cell lineages. Recently, it has been implicated in development and maintenance of immune cells in barrier tissues such as skin and mucosa. To investigate its role on mast cell development and maintenance in skin, peritoneal exudate cells (PECs) and lymph nodes, we studied in depth their phenotype in AhR-deficient mice. Our findings do not provide any evidence for a suspected role of the AhR in mast cell homeostasis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

PubMed Central

Engelhardt, Othmar G.; Wood, John; Heath, Alan; Katz, Jacqueline M.; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D.

2015-01-01

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future. PMID:26108286

A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

PubMed

de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

2008-10-22

Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.

NcoA2-Dependent Inhibition of HIF-1α Activation Is Regulated via AhR.

PubMed

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

2015-12-01

High endogenous levels of aryl hydrocarbon receptor (AhR) contribute to hypoxia signaling pathway inhibition following exposure to the potent AhR ligand benzo[a]pyrene (B[a]P) and could alter cellular homeostasis and disease condition. Increasing evidence indicates that AhR might compete with AhR nuclear translocator (ARNT) for complex formation with hypoxia-inducible factor-1α (HIF-1α) for transactivation, which could alter several physiological variables. Nuclear receptor coactivator 2 (NcoA2) is a transcription coactivator that regulates transcription factor activation and inhibition of basic helix-loop-helix Per (Period)-ARNT-SIM (single-minded) (bHLH-PAS) family proteins, such as HIF-1α, ARNT, and AhR, through protein-protein interactions. In this study, we demonstrated that both hypoxia and hypoxia-mimic conditions decreased NcoA2 protein expression in HEK293T cells. Hypoxia response element (HRE) and xenobiotic-responsive element (XRE) transactivation also were downregulated with NcoA2 knockdown under hypoxic conditions. In addition, B[a]P significantly decreased NcoA2 protein expression be accompanied with AhR degradation. We next evaluated whether the absence of AhR could affect NcoA2 protein function under hypoxia-mimetic conditions. NcoA2 and HIF-1α nuclear localization decreased in both B[a]P-pretreated and AhR-knockdown HepG2 cells under hypoxia-mimic conditions. Interestingly, NcoA2 overexpression downregulated HRE transactivation by competing with HIF-1α and AhR to form protein complexes with ARNT. Both NcoA2 knockdown and overexpression inhibited endothelial cell tube formation in vitro. We also demonstrated using the in vivo plug assay that NcoA2-regulated vascularization decreased in mice. Taken together, these results revealed a biphasic role of NcoA2 between AhR and hypoxic conditions, thus providing a novel mechanism underlying the cross talk between AhR and hypoxia that affects disease development and progression. © The Author 2015

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

PubMed

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.

IEEE 802.11ah: A Technology to Face the IoT Challenge

PubMed Central

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

2016-01-01

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. PMID:27879688

ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR.

PubMed

Li, Yan; Wang, Kai; Zou, Qing-Yun; Jiang, Yi-Zhou; Zhou, Chi; Zheng, Jing

2017-12-01

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is involved in regulation of many essential biological processes including vascular development and angiogenesis. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an AhR ligand, which regulates immune responses and cancer cell growth. However, the roles of the ITE/AhR pathway in mediating placental angiogenesis remains elusive. Here, we determined if ITE affected placental angiogenic responses via AhR in human umbilical vein (HUVECs) and artery endothelial (HUAECs) cells in vitro. We observed that ITE dose- and time-dependently inhibited proliferation and viability of HUAECs and HUVECs, whereas it inhibited migration of HUAECs, but not HUVECs. While AhR siRNA significantly suppressed AhR protein expression in HUVECs and HUAECs, it attenuated the ITE-inhibited angiogenic responses of HUAECs, but not HUVECs. Collectively, ITE suppressed angiogenic responses of HUAECs and HUVECs, dependent and independent of AhR, respectively. These data suggest that ITE may regulate placental angiogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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. Copyright © 2015 Elsevier GmbH. All rights reserved.

Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

PubMed

Park, Wook Ha; Kang, Sora; Lee, Hong Kyu; Salihovic, Samira; Bavel, Bert van; Lind, P Monica; Pak, Youngmi Kim; Lind, Lars

2017-08-24

Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum samples obtained from 911 elderly subjects in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Plasma concentrations of 30 POPs and plastic chemicals have previously been determined in the same PIVUS subjects. Linear regression analysis demonstrated that total toxic equivalence (TEQ) values and polychlorinated biphenyls (PCBs) were significantly correlated with AhR bioactivity (positively) and ATP concentration (negatively). Serum AhR bioactivities were positively associated with some PCBs, regardless of their dioxin-like properties, but only dioxin-like PCBs stimulated AhR bioactivity. By contrast, PCBs mediated a reduction in ATP content independently of their dioxin-like properties. This study suggests that AhR bioactivity and ATP concentrations in serum-treated cells may be valuable surrogate biomarkers of POP exposure and could be useful for the estimation of the effects of POPs on human health.

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

PubMed

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. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Thromboembolic events in patients with severe pandemic influenza A/H1N1.

PubMed

Avnon, Lone Sølling; Munteanu, Daniela; Smoliakov, Alexander; Jotkowitz, Alan; Barski, Leonid

2015-10-01

The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Cell and region specificity of Aryl hydrocarbon Receptor (AhR) system in the testis and the epididymis.

PubMed

Wajda, A; Łapczuk, J; Grabowska, M; Pius-Sadowska, E; Słojewski, M; Laszczynska, M; Urasinska, E; Machalinski, B; Drozdzik, M

2017-04-01

Aryl hydrocarbon receptor (AhR) plays multiple important functions in adaptive responses. Exposure to AhR ligands may produce an altered metabolic activity controlled by the AhR pathways, and consequently affect drug/toxin responses, hormonal status and cellular homeostasis. This research revealed species-, cell- and region-specific pattern of the AhR system expression in the rat and human testis and epididymis, complementing the existing knowledge, especially within the epididymal segments. The study showed that AhR level in the rat and human epididymis is higher than in the testis. The downregulation of AhR expression after TCDD treatment was revealed in the spermatogenic cells at different stages and the epididymal epithelial cells, but not in the Sertoli and Leydig cells. Hence, this basic research provides information about the AhR function in the testis and epididymis, which may provide an insight into deleterious effects of drugs, hormones and environmental pollutants on male fertility. Copyright © 2017 Elsevier Inc. All rights reserved.

The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells

PubMed Central

Ibabao, Christopher N.; Bunaciu, Rodica P.; Schaefer, Deanna M.W.; Yen, Andrew

2015-01-01

In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14+CD11b+ monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627

The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.

PubMed

Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W; Yen, Andrew

2015-01-01

In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr.

Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010

PubMed Central

Van Effelterre, Thierry; Dos Santos, Gaël; Shinde, Vivek

2016-01-01

Background Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. Methods A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. Results The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10–20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10–20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. Conclusion This analysis

AH Leo and the Blazhko Effect

NASA Astrophysics Data System (ADS)

Phillips, J.; Gay, P. L.

2004-12-01

We obtained 563 V-Band observations of AH Leo between January 27 and May 12, 2004. All observations were obtained with a 12-inch Schmidt-Cassegrain located on the island of Saipan, in the Commonwealth of the Northern Mariana Islands. We show that AH Leo is a type RRab RR Lyrae star with a minimum magnitude of V=14.658 magnitudes, a maximum amplitude of 0.989 magnitudes and a minimum amplitude of perhaps just 0.4 magnitudes. Its primary period is 0.4662609 days. Our observations also confirm the presence of the Blazhko effect, which had previously been detected by Smith and Gay (private communication) in 1993 and 1994. We estimate the Blazhko period to be roughly 20-days, however poor phase coverage at maximum light makes exact determination impossible. We also note that the bump during minimum, which is common in many RR Lyraes, varied throughout the Blazhko cycle, demonstrating amplitudes between 0 and 0.15 magnitudes. We would like to thank Sarah Maddison and Swinburne Astronomy Online for supporting this project

AhR and Arnt differentially regulate NF-κB signaling and chemokine responses in human bronchial epithelial cells

PubMed Central

2014-01-01

Background The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). Results Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. Conclusion AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5

A Modified Delphi Study to Define "Ah Ha" Moments in Education Settings

ERIC Educational Resources Information Center

Pilcher, Jobeth

2015-01-01

Ah ha moments are often mentioned in education literature. These moments are suggested to be a powerful aspect of learning, yet limited research is present regarding this topic. Ah ha learning moments have also not been defined in the education literature, resulting in the likelihood that each educator and learner may have differing definitions.…

Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.

PubMed

Kimura, Eiki; Kubo, Ken-Ichiro; Endo, Toshihiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

2017-01-01

The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain. We transfected constitutively active (CA)-AhR, AhR, or control vector plasmids into neurons via in utero electroporation on gestational day 14 and analyzed neuronal positioning in the hippocampal CA1 region of offspring on postnatal day 14. CA-AhR transfection affected neuronal positioning, whereas no change was observed in AhR-transfected or control hippocampus. These results suggest that constitutively activated AhR signaling disrupts neuronal migration during hippocampal development. Further studies are needed to investigate whether such developmental disruption in the hippocampus leads to the abnormal cognition and behavior of rodent offspring upon maternal exposure to AhR xenobiotic ligands.

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

PubMed

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

2017-01-01

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

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

PubMed

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

2016-05-01

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas through unknown molecular mechanisms. The best-known interacting partner of AIP is the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the effects of xenobiotics implicated in carcinogenesis. As 75% of AIP mutations disrupt the physical and/or functional interaction with AhR, we postulated that the tumorigenic potential of AIP mutations might result from altered AhR signaling. We evaluated the impact of AIP mutations on the AhR signaling pathway, first in fibroblasts from AIP-mutated patients with pituitary adenomas, by comparison with fibroblasts from healthy subjects, then in transfected pituitary GH3 cells. The AIP protein level in mutated fibroblasts was about half of that in cells from healthy subjects, but AhR expression was unaffected. Gene expression analyses showed significant modifications in the expression of the AhR target genes CYP1B1 and AHRR in AIP-mutated fibroblasts, both before and after stimulation with the endogenous AhR ligand kynurenine. Kynurenine increased Cyp1b1 expression to a greater extent in GH3 cells overexpressing wild type compared with cells expressing mutant AIP Knockdown of endogenous Aip in these cells attenuated Cyp1b1 induction by the AhR ligand. Both mutant AIP expression and knockdown of endogenous Aip affected the kynurenine-dependent GH secretion of GH3 cells. This study of human fibroblasts bearing endogenous heterozygous AIP mutations and transfected pituitary GH3 cells shows that AIP mutations affect the AIP protein level and alter AhR transcriptional activity in a gene- and tissue-dependent manner. © 2016 Society for Endocrinology.

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China

PubMed Central

Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Peiris, Joseph Sriyal Malik

2017-01-01

The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient’s adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread. PMID:28580899

Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China.

PubMed

Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Yang, Zifeng; Shu, Yuelong; Peiris, Joseph Sriyal Malik

2017-07-01

The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.

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

PubMed Central

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

2016-01-01

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

Transmission potential of influenza A/H7N9, February to May 2013, China

PubMed Central

2013-01-01

Background On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness. Methods We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses. Results Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated

Negative feedback regulation of ABA biosynthesis in peanut (Arachis hypogaea): a transcription factor complex inhibits AhNCED1 expression during water stress

PubMed Central

Liu, Shuai; Li, Meijuan; Su, Liangchen; Ge, Kui; Li, Limei; Li, Xiaoyun; Liu, Xu; Li, Ling

2016-01-01

Abscisic acid (ABA), a key plant stress-signaling hormone, is produced in response to drought and counteracts the effects of this stress. The accumulation of ABA is controlled by the enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). In Arabidopsis, NCED3 is regulated by a positive feedback mechanism by ABA. In this study in peanut (Arachis hypogaea), we demonstrate that ABA biosynthesis is also controlled by negative feedback regulation, mediated by the inhibitory effect on AhNCED1 transcription of a protein complex between transcription factors AhNAC2 and AhAREB1. AhNCED1 was significantly down-regulated after PEG treatment for 10 h, at which time ABA content reached a peak. A ChIP-qPCR assay confirmed AhAREB1 and AhNAC2 binding to the AhNCED1 promoter in response to ABA. Moreover, the interaction between AhAREB1 and AhNAC2, and a transient expression assay showed that the protein complex could negatively regulate the expression of AhNCED1. The results also demonstrated that AhAREB1 was the key factor in AhNCED1 feedback regulation, while AhNAC2 played a subsidiary role. ABA reduced the rate of AhAREB1 degradation and enhanced both the synthesis and degradation rate of the AhNAC2 protein. In summary, the AhAREB1/AhNAC2 protein complex functions as a negative feedback regulator of drought-induced ABA biosynthesis in peanut. PMID:27892506

Introducing the "TCDD-inducible AhR-Nrf2 gene battery".

PubMed

Yeager, Ronnie L; Reisman, Scott A; Aleksunes, Lauren M; Klaassen, Curtis D

2009-10-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the "AhR gene battery." However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 mug/kg, ip) to Nrf2-null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid-synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice.

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

PubMed

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

2016-12-15

The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow-derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, bone marrow macrophages isolated from AhR -/- mice exhibited impaired phosphorylation of Akt and MAPK as well as NF-κB, whereas their response to M-CSF remained unchanged. Osteoclast differentiation mediated by the AhR signaling pathway was also regulated in an RANKL/c-Fos-dependent manner. Furthermore, ligand activation of AhR by the smoke toxin benzo[a]pyrene accelerated osteoclast differentiation in a receptor-dependent manner, and AhR-dependent regulation of mitochondrial biogenesis in osteoclasts was observed. Moreover, AhR -/- mice exhibited impaired bone healing with delayed endochondral ossification. Taken together, the present results suggest that the RANKL/AhR/c-Fos signaling axis plays a critical role in osteoclastogenesis, thereby identifying the potential of AhR in treating pathological, inflammatory, or metabolic disorders of the bone. Copyright © 2016 by The American Association of Immunologists, Inc.

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

PubMed

Drozdzik, Agnieszka; Kowalczyk, Robert; Lipski, Mariusz; Łapczuk, Joanna; Urasinska, Elzbieta; Kurzawski, Mateusz

2016-01-01

Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma. Copyright © 2015. Published by Elsevier Ltd.

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

PubMed

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

2015-01-01

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

The influence of social-cognitive factors on personal hygiene practices to protect against influenzas: using modelling to compare avian A/H5N1 and 2009 pandemic A/H1N1 influenzas in Hong Kong.

PubMed

Liao, Qiuyan; Cowling, Benjamin J; Lam, Wendy Wing Tak; Fielding, Richard

2011-06-01

Understanding population responses to influenza helps optimize public health interventions. Relevant theoretical frameworks remain nascent. To model associations between trust in information, perceived hygiene effectiveness, knowledge about the causes of influenza, perceived susceptibility and worry, and personal hygiene practices (PHPs) associated with influenza. Cross-sectional household telephone surveys on avian influenza A/H5N1 (2006) and pandemic influenza A/H1N1 (2009) gathered comparable data on trust in formal and informal sources of influenza information, influenza-related knowledge, perceived hygiene effectiveness, worry, perceived susceptibility, and PHPs. Exploratory factor analysis confirmed domain content while confirmatory factor analysis was used to evaluate the extracted factors. The hypothesized model, compiled from different theoretical frameworks, was optimized with structural equation modelling using the A/H5N1 data. The optimized model was then tested against the A/H1N1 dataset. The model was robust across datasets though corresponding path weights differed. Trust in formal information was positively associated with perceived hygiene effectiveness which was positively associated with PHPs in both datasets. Trust in formal information was positively associated with influenza worry in A/H5N1 data, and with knowledge of influenza cause in A/H1N1 data, both variables being positively associated with PHPs. Trust in informal information was positively associated with influenza worry in both datasets. Independent of information trust, perceived influenza susceptibility associated with influenza worry. Worry associated with PHPs in A/H5N1 data only. Knowledge of influenza cause and perceived PHP effectiveness were associated with PHPs. Improving trust in formal information should increase PHPs. Worry was significantly associated with PHPs in A/H5N1.

Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway.

PubMed

Takei, Kenjiro; Hashimoto-Hachiya, Akiko; Takahara, Masakazu; Tsuji, Gaku; Nakahara, Takeshi; Furue, Masutaka

2015-04-16

Due to its antioxidant and anti-inflammatory activities, artichoke (Cynara scolymus) has been used as folk medicine to treat various diseases. Cynaropicrin (Cyn), a sesquiterpene lactone, is the major bioactive phytochemical in the artichoke; however, its pharmacological mechanism remains unknown. Because some phytochemicals exert their antioxidant activity by activating aryl hydrocarbon receptor (AhR), leading to subsequent induction of the antioxidant pathway including nuclear factor E2-related factor 2 (Nrf2) and quinone oxidoreductase 1 (Nqo1), we investigated whether Cyn also activates the AhR-Nrf2-Nqo1 pathway. Cyn indeed induced the activation (nuclear translocation) of AhR, leading to nuclear translocation of Nrf2 and dose-dependent upregulation of Nrf2 and Nqo1 mRNAs in human keratinocytes. The Cyn-induced AhR-Nrf2-Nqo1 activation was AhR- and Nrf2-dependent, as demonstrated by the observation that it was absent in keratinocytes transfected by siRNA against either AhR or Nrf2. In accordance with these findings, Cyn actively inhibited generation of reactive oxygen species from keratinocytes irradiated with ultraviolet B (UVB) in a Nrf2-dependent manner. Cyn also inhibited the production of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor-α from UVB-treated keratinocytes. Our findings demonstrate that Cyn is a potent activator of the AhR-Nrf2-Nqo1 pathway, and could therefore be applied to prevention of UVB-induced photo aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Summary of AH-1G flight vibration data for validation of coupled rotor-fuselage analyses

NASA Technical Reports Server (NTRS)

Dompka, R. V.; Cronkhite, J. D.

1986-01-01

Under a NASA research program designated DAMVIBS (Design Analysis Methods for VIBrationS), four U. S. helicopter industry participants (Bell Helicopter, Boeing Vertol, McDonnell Douglas Helicopter, and Sikorsky Aircraft) are to apply existing analytical methods for calculating coupled rotor-fuselage vibrations of the AH-1G helicopter for correlation with flight test data from an AH-1G Operational Load Survey (OLS) test program. Bell Helicopter, as the manufacturer of the AH-1G, was asked to provide pertinent rotor data and to collect the OLS flight vibration data needed to perform the correlations. The analytical representation of the fuselage structure is based on a NASTRAN finite element model (FEM) developed by Bell which has been extensively documented and correlated with ground vibration tests.The AH-1G FEM was provided to each of the participants for use in their coupled rotor-fuselage analyses. This report describes the AH-1G OLS flight test program and provides the flight conditions and measured vibration data to be used by each participant in their correlation effort. In addition, the mechanical, structural, inertial and aerodynamic data for the AH-1G two-bladed teetering main rotor system are presented. Furthermore, modifications to the NASTRAN FEM of the fuselage structure that are necessary to make it compatible with the OLS test article are described. The AH-1G OLS flight test data was found to be well documented and provide a sound basis for evaluating currently existing analysis methods used for calculation of coupled rotor-fuselage vibrations.

Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure.

PubMed

Rogers, Sarah; de Souza, Angela Rico; Zago, Michela; Iu, Matthew; Guerrina, Necola; Gomez, Alvin; Matthews, Jason; Baglole, Carolyn J

2017-01-12

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr -/- and Ahr +/- mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr -/- mice compared to Ahr +/- mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease.

Influenza A(H1N1)v in Germany: the first 10,000 cases.

PubMed

Gilsdorf, Andreas; Poggensee, Gabriele

2009-08-27

The analysis of the first 10,000 cases of influenza A(H1N1)v in Germany confirms findings from other sources that the virus is currently mainly causing mild diseases, affecting mostly adolescents and young adults. Overall hospitalisation rate for influenza A(H1N1)v was low (7%). Only 3% of the cases had underlying conditions and pneumonia was rare (0.4%). Both reporting and testing requirements have been adapted recently, taking into consideration the additional information available on influenza A(H1N1)v infections.

Studies on the Role of The Ah Receptor (AhR) on the Etiology of Breast Cancer: A Novel Idea of Identifying this Receptor as a New Therapeutic Target

DTIC Science & Technology

2010-09-01

found that the most potent phytochemical suppressors of cell proliferation of P20E cells were curcumin (10 µM approximately 80 to 90% suppression...effectiveness of a number of phytochemicals from edible plants known to block AhR in attenuating the expression of high rates of cell proliferation...selected number of those phytochemicals , by xenografting those AhR overexpressing human breast cancer cells into athymic nude mice, and by treating

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

PubMed Central

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

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(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

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.

PubMed

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

Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection.

PubMed

Wang, Yeming; Guo, Qiang; Yan, Zheng; Zhou, Daming; Zhang, Wei; Zhou, Shujun; Li, Yu-Ping; Yuan, Jing; Uyeki, Timothy M; Shen, Xinghua; Wu, Wenjuan; Zhao, Hui; Wu, Yun-Fu; Shang, Jia; He, Zhengguang; Yang, Yi; Zhao, Hongsheng; Hong, Yongqing; Zhang, Zehua; Wu, Min; Wei, Tiemin; Deng, Xilong; Deng, Yijun; Cai, Li-Hua; Lu, Weihua; Shu, Hongmei; Zhang, Lin; Luo, Hong; Ing Zhou, Y; Weng, Heng; Song, Keyi; Yao, Li; Jiang, Mingguang; Zhao, Boliang; Chi, Ruibin; Guo, Boqi; Fu, Lin; Yu, Long; Min, Haiyan; Chen, Pu; Chen, Shuifang; Hong, Liang; Mao, Wei; Huang, Xiaoping; Gu, Lijun; Li, Hui; Wang, Chen; Cao, Bin

2018-05-05

Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans.

PubMed

Smith, Susan H; Jayawickreme, Channa; Rickard, David J; Nicodeme, Edwige; Bui, Thi; Simmons, Cathy; Coquery, Christine M; Neil, Jessica; Pryor, William M; Mayhew, David; Rajpal, Deepak K; Creech, Katrina; Furst, Sylvia; Lee, James; Wu, Dalei; Rastinejad, Fraydoon; Willson, Timothy M; Viviani, Fabrice; Morris, David C; Moore, John T; Cote-Sierra, Javier

2017-10-01

Tapinarof (GSK2894512) is a naturally derived topical treatment with demonstrated efficacy for patients with psoriasis and atopic dermatitis, although the biologic target and mechanism of action had been unknown. We demonstrate that the anti-inflammatory properties of tapinarof are mediated through activation of the aryl hydrocarbon receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue-human skin. In addition, tapinarof moderates proinflammatory cytokine expression in stimulated peripheral blood CD4+ T cells and ex vivo human skin, and impacts barrier gene expression in primary human keratinocytes; both of these processes are likely to be downstream of AhR activation based on current evidence. That the anti-inflammatory properties of tapinarof derive from AhR agonism is conclusively demonstrated using the mouse model of imiquimod-induced psoriasiform skin lesions. Topical treatment of AhR-sufficient mice with tapinarof leads to compound-driven reductions in erythema, epidermal thickening, and tissue cytokine levels. In contrast, tapinarof has no impact on imiquimod-induced skin inflammation in AhR-deficient mice. In summary, these studies identify tapinarof as an AhR agonist and confirm that its efficacy is dependent on AhR. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The aryl hydrocarbon receptor repressor - More than a simple feedback inhibitor of AhR signaling: Clues for its role in inflammation and cancer.

PubMed

Vogel, Christoph F A; Haarmann-Stemmann, Thomas

2017-02-01

The aryl hydrocarbon receptor repressor (AhRR) was first described as a specific competitive repressor of aryl hydrocarbon receptor (AhR) activity based on its ability to dimerize with the AhR nuclear translocator (ARNT) and through direct competition of AhR/ARNT and AhRR/ARNT complexes for binding to dioxin-responsive elements (DREs). Like AhR, AhRR belongs to the basic Helix-Loop-Helix/Per-ARNT-Sim (bHLH/PAS) protein family but lacks functional ligand-binding and transactivation domains. Transient transfection experiments with ARNT and AhRR mutants examining the inhibitory mechanism of AhRR suggested a more complex mechanism than the simple mechanism of negative feedback through sequestration of ARNT to regulate AhR signaling. Recently, AhRR has been shown to act as a tumor suppressor gene in several types of cancer cells. Furthermore, epidemiological studies have found epigenetic changes and silencing of AhRR associated with exposure to cigarette smoke and cancer development. Additional studies from our laboratories have demonstrated that AhRR represses other signaling pathways including NF-κB and is capable of regulating inflammatory responses. A better understanding of the regulatory mechanisms of AhRR in AhR signaling and adverse outcome pathways leading to deregulated inflammatory responses contributing to tumor promotion and other adverse health effects is expected from future studies. This review article summarizes the characteristics of AhRR as an inhibitor of AhR activity and highlights more recent findings pointing out the role of AhRR in inflammation and tumorigenesis.

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

PubMed

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.

Novel cellular targets of AhR underlie alterations in neutrophilic inflammation and iNOS expression during influenza virus infection

PubMed Central

Head Wheeler, Jennifer L.; Martin, Kyle C.; Lawrence, B. Paige

2012-01-01

The underlying reasons for variable clinical outcomes from respiratory viral infections remain uncertain. Several studies suggest that environmental factors contribute to this variation, but limited knowledge of cellular and molecular targets of these agents hampers our ability to quantify or modify their contribution to disease and improve public health. The aryl hydrocarbon receptor (AhR) is an environment sensing transcription factor that binds many anthropogenic and natural chemicals. The immunomodulatory properties of AhR ligands are best characterized with extensive studies of changes in CD4+ T cell responses. Yet, AhR modulates other aspects of immune function. We previously showed that during influenza virus infection, AhR activation modulates neutrophil accumulation in the lung, and this contributes to increased mortality in mice. Enhanced levels of inducible nitric oxide synthase (iNOS) in infected lungs are observed during the same timeframe as AhR-mediated increased pulmonary neutrophilia. In this study, we evaluated whether these two consequences of AhR activation are causally linked. Reciprocal inhibition of AhR-mediated elevations in iNOS and pulmonary neutrophilia reveal that, although they are contemporaneous, they are not causally related. We show using Cre/loxP technology that elevated iNOS levels and neutrophil number in the infected lung result from separate, AhR-dependent signaling in endothelial and respiratory epithelial cells, respectively. Studies using mutant mice further reveal that AhR-mediated alterations in these innate responses to infection require a functional nuclear localization signal and DNA binding domain. Thus, gene targets of AhR in non-hematopoietic cells are important new considerations for understanding AhR-mediated changes in innate anti-viral immunity. PMID:23233726

AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing.

PubMed

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.

Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure

PubMed Central

Rogers, Sarah; de Souza, Angela Rico; Zago, Michela; Iu, Matthew; Guerrina, Necola; Gomez, Alvin; Matthews, Jason; Baglole, Carolyn J.

2017-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr−/− and Ahr+/− mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr−/− mice compared to Ahr+/− mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease. PMID:28079158

Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

PubMed

Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

2011-03-23

The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state--Implications for the Hepatitis C virus life cycle.

PubMed

Ashworth Briggs, Esther L; Gomes, Rafael G B; Elhussein, Malaz; Collier, William; Findlow, I Stuart; Khalid, Syma; McCormick, Chris J; Williamson, Philip T F

2015-08-01

The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Is chronic AhR activation by rapidly metabolized ligands safe for the treatment of immune-mediated diseases?

PubMed

Ehrlich, Allison K; Kerkvliet, Nancy I

2017-02-01

There is a long standing perception that AhR ligands are automatically disqualified from pharmaceutical development due to their induction of Cyp1a1 as well as their potential for causing "dioxin-like" toxicities. However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy. One area of exploration is focused on the activation of AhR to promote the generation of regulatory T cells, which control the intensity and duration of immune responses. Rapidly metabolized AhR ligands (RMAhRLs), which do not bioaccumulate in the same manner as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) have been discovered that induce Tregs and display impressive therapeutic efficacy in a broad range of preclinical models of immune-mediated diseases. Given the promise of these RMAhRLs, is the bias against AhR activators still valid? Can RMAhRLs be given chronically to maintain therapeutic levels of AhR activation without producing the same toxicity profile as dioxin-like compounds? Based on our review of the data, there is little evidence to support the indiscriminate exclusion of AhR activators/Cyp1a1 inducers from early drug developmental pipelines. We also found no evidence that short-term treatment with RMAhRLs produce "dioxin-like toxicity" and, in fact, were well tolerated. However, safety testing of individual RMAhRLs under therapeutic conditions, as performed with all promising new drugs, will be needed to reveal whether or not chronic activation of AhR leads to unacceptable adverse outcomes.

Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells.

PubMed

Brenerová, Petra; Hamers, Timo; Kamstra, Jorke H; Vondráček, Jan; Strapáčová, Simona; Andersson, Patrik L; Machala, Miroslav

2016-02-01

The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC50 values from 1.4 to 5.6 μM), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.

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

PubMed Central

Chen, Silong; Lei, Yong; Xu, Xian; Huang, Jiaquan; Jiang, Huifang; Wang, Jin; Cheng, Zengshu; Zhang, Jianan; Song, Yahui; Liao, Boshou; Li, Yurong

2015-01-01

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. PMID:26302041

Apoptotic cell-induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans.

PubMed

Shinde, Rahul; Hezaveh, Kebria; Halaby, Marie Jo; Kloetgen, Andreas; Chakravarthy, Ankur; da Silva Medina, Tiago; Deol, Reema; Manion, Kieran P; Baglaenko, Yuriy; Eldh, Maria; Lamorte, Sara; Wallace, Drew; Chodisetti, Sathi Babu; Ravishankar, Buvana; Liu, Haiyun; Chaudhary, Kapil; Munn, David H; Tsirigos, Aristotelis; Madaio, Michael; Gabrielsson, Susanne; Touma, Zahi; Wither, Joan; De Carvalho, Daniel D; McGaha, Tracy L

2018-06-01

The transcription factor AhR modulates immunity at multiple levels. Here we report that phagocytes exposed to apoptotic cells exhibited rapid activation of AhR, which drove production of the cytokine IL-10. Activation of AhR was dependent on interactions between apoptotic-cell DNA and the pattern-recognition receptor TLR9 that was required for the prevention of immune responses to DNA and histones in vivo. Moreover, disease progression in mouse systemic lupus erythematosus (SLE) correlated with strength of the AhR signal, and the disease course could be altered by modulation of AhR activity. Deletion of AhR in the myeloid lineage caused systemic autoimmunity in mice, and an enhanced AhR transcriptional signature correlated with disease in patients with SLE. Thus, AhR activity induced by apoptotic cell phagocytes maintains peripheral tolerance.

Binding Mode and Structure-Activity Relationships of ITE as an Aryl Hydrocarbon Receptor (AhR) Agonist.

PubMed

Dolciami, Daniela; Gargaro, Marco; Cerra, Bruno; Scalisi, Giulia; Bagnoli, Luana; Servillo, Giuseppe; Fazia, Maria Agnese Della; Puccetti, Paolo; Quintana, Francisco J; Fallarino, Francesca; Macchiarulo, Antonio

2018-02-06

Discovered as a modulator of the toxic response to environmental pollutants, aryl hydrocarbon receptor (AhR) has recently gained attention for its involvement in various physiological and pathological pathways. AhR is a ligand-dependent transcription factor activated by a large array of chemical compounds, which include metabolites of l-tryptophan (l-Trp) catabolism as endogenous ligands of the receptor. Among these, 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester (ITE) has attracted interest in the scientific community, being endowed with nontoxic, immunomodulatory, and anticancer AhR-mediated functions. So far, no information about the binding mode and interactions of ITE with AhR is available. In this study, we used docking and molecular dynamics to propose a putative binding mode of ITE into the ligand binding pocket of AhR. Mutagenesis studies were then instrumental in validating the proposed binding mode, identifying His 285 and Tyr 316 as important key residues for ligand-dependent receptor activation. Finally, a set of ITE analogues was synthesized and tested to further probe molecular interactions of ITE to AhR and characterize the relevance of specific functional groups in the chemical structure for receptor activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estrogenic and AhR activities in dissolved phase and suspended solids from wastewater treatment plants.

PubMed

Dagnino, Sonia; Gomez, Elena; Picot, Bernadette; Cavaillès, Vincent; Casellas, Claude; Balaguer, Patrick; Fenet, Hélène

2010-05-15

The distribution of estrogen receptor (ERalpha) and Aryl Hydrocarbon Receptor (AhR) activities between the dissolved phase and suspended solids were investigated during wastewater treatment. Three wastewater treatment plants with different treatment technologies (waste stabilization ponds (WSPs), trickling filters (TFs) and activated sludge supplemented with a biofilter system (ASB)) were sampled. Estrogenic and AhR activities were detected in both phases in influents and effluents. Estrogenic and AhR activities in wastewater influents ranged from 41.8 to 79 ng/L E(2) Eq. and from 37.9 to 115.5 ng/L TCDD Eq. in the dissolved phase and from 5.5 to 88.6 ng/g E(2) Eq. and from 15 to 700 ng/g TCDD Eq. in the suspended solids. For both activities, WSP showed greater or similar removal efficiency than ASB and both were much more efficient than TF which had the lowest removal efficiency. Moreover, our data indicate that the efficiency of removal of ER and AhR activities from the suspended solid phase was mainly due to removal of suspended solids. Indeed, ER and AhR activities were detected in the effluent suspended solid phase indicating that suspended solids, which are usually not considered in these types of studies, contribute to environmental contamination by endocrine disrupting compounds and should therefore be routinely assessed for a better estimation of the ER and AhR activities released in the environment. Copyright 2010 Elsevier B.V. All rights reserved.

Assessing evidence for avian-to-human transmission of influenza A/H9N2 virus in rural farming communities in northern Vietnam

PubMed Central

Hoa, Le Nguyen Minh; Tuan, Nguyen Anh; My, Pham Ha; Huong, Tran Thi Kieu; Chi, Nguyen Thi Yen; Hau Thu, Trang Thi; Carrique-Mas, Juan; Duong, Mai Thuy; Tho, Nguyen Dang; Hoang, Nguyen Dang; Thanh, To Long; Diep, Nguyen Thi; van Duong, Nguyen; Toan, Tran Khanh; Tung, Trinh Son; Mai, Le Quynh; Iqbal, Munir; Wertheim, Heiman; van Doorn, H. Rogier

2017-01-01

Rural farming communities in northern Vietnam do not routinely practice vaccination for influenza A viruses (IAV) for either humans or poultry, which enables us to study transmission intensity via seroepidemiology. Using samples from a longitudinal cohort of farming households, we determined the number of symptomatic and asymptomatic human infections for seasonal IAV and avian A/H9 over 2 years. As expected, we detected virologically confirmed acute cases of seasonal IAV in humans, as well as large numbers of subclinical seroconversions to A/H1pdm [55/265 (21 %)], A/H3 [95/265 (36 %)] and A/H9 [24/265 (9 %)]. Five of the A/H9 human seroconverters likely represented true infections rather than heterosubtypic immunity, because the individuals seroconverted solely to A/H9. Among co-located poultry, we found significantly higher seroprevalance for A/H5 compared to A/H9 in both chickens and ducks [for northern study sites overall, 337/1105 (30.5 %) seropositive for A/H5 and 123/1105 (11.1 %) seropositive for A/H9]. PMID:28771136

Assessing evidence for avian-to-human transmission of influenza A/H9N2 virus in rural farming communities in northern Vietnam.

PubMed

Hoa, Le Nguyen Minh; Tuan, Nguyen Anh; My, Pham Ha; Huong, Tran Thi Kieu; Chi, Nguyen Thi Yen; Hau Thu, Trang Thi; Carrique-Mas, Juan; Duong, Mai Thuy; Tho, Nguyen Dang; Hoang, Nguyen Dang; Thanh, To Long; Diep, Nguyen Thi; Duong, Nguyen van; Toan, Tran Khanh; Tung, Trinh Son; Mai, Le Quynh; Iqbal, Munir; Wertheim, Heiman; van Doorn, H Rogier; Bryant, Juliet E; The Vizions Consortium

2017-08-01

Rural farming communities in northern Vietnam do not routinely practice vaccination for influenza A viruses (IAV) for either humans or poultry, which enables us to study transmission intensity via seroepidemiology. Using samples from a longitudinal cohort of farming households, we determined the number of symptomatic and asymptomatic human infections for seasonal IAV and avian A/H9 over 2 years. As expected, we detected virologically confirmed acute cases of seasonal IAV in humans, as well as large numbers of subclinical seroconversions to A/H1pdm [55/265 (21 %)], A/H3 [95/265 (36 %)] and A/H9 [24/265 (9 %)]. Five of the A/H9 human seroconverters likely represented true infections rather than heterosubtypic immunity, because the individuals seroconverted solely to A/H9. Among co-located poultry, we found significantly higher seroprevalance for A/H5 compared to A/H9 in both chickens and ducks [for northern study sites overall, 337/1105 (30.5 %) seropositive for A/H5 and 123/1105 (11.1 %) seropositive for A/H9].

Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms.

PubMed

Bonati, Laura; Corrada, Dario; Tagliabue, Sara Giani; Motta, Stefano

2017-02-01

Molecular modeling has given important contributions to elucidation of the main stages in the AhR signal transduction pathway. Despite the lack of experimentally determined structures of the AhR functional domains, information derived from homologous systems has been exploited for modeling their structure and interactions. Homology models of the AhR PASB domain have provided information on the binding cavity and contributed to elucidate species-specific differences in ligand binding. Molecular Docking simulations of the ligand binding process have given insights into differences in binding of diverse agonists, antagonists, and selective AhR modulators, and their application to virtual screening of large databases of compounds have allowed identification of novel AhR ligands. Recently available structural information on protein-protein and protein-DNA complexes of other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer structure and investigating the mechanisms of AhR transformation and DNA binding. Future research directions should include simulation of the protein dynamics to obtain a more reliable description of intermolecular interactions involved in signal transmission.

Involvement of the cytokine-IDO1-AhR loop in zinc oxide nanoparticle-induced acute pulmonary inflammation.

PubMed

Ho, Chia-Chi; Lee, Hui-Ling; Chen, Chao-Yu; Luo, Yueh-Hsia; Tsai, Ming-Hsien; Tsai, Hui-Ti; Lin, Pinpin

2017-04-01

Zinc oxide nanoparticles (ZnONPs) are widely used in our daily life, such as in sunscreens and electronic nanodevices. However, pulmonary exposure to ZnONPs causes acute pulmonary inflammation, which is considered as an initial event for various respiratory diseases. Thus, elucidation of the underlying cellular mechanisms of ZnONPs can help us in predicting their potential effects in respiratory diseases. In this study, we observed that ZnONPs increased proinflammatory cytokines, accompanied with an increased expression of aryl hydrocarbon receptor (AhR) and its downstream target cytochrome P450 1A1 (CYP1A1) in macrophages in vitro and in mouse lung epithelia in vivo. Moreover, zinc nitrate, but not silica or titanium dioxide nanoparticles (NPs), had similar effects on macrophages, indicating that the zinc element or ion released from ZnONPs is likely responsible for the activation of the AhR pathway. Cotreatment with an AhR antagonist or AhR knockout reduced ZnONPs-induced cytokine secretion in macrophages or mice, respectively. Furthermore, kynurenine (KYN), an endogenous AhR agonist and a tryptophan metabolite catalyzed by indoleamine 2,3-dioxygenase (IDO), was increased in the serums of mice that aspirated ZnONPs. Consistently, ZnONPs increased IDO1 expression in lung cells in vitro and in vivo. Finally, AhR knockout reduced ZnONPs-induced pulmonary inflammation, cytokine secretion and KYN production in mice, suggesting that AhR activation is involved in ZnONPs-induced cytokine secretion and pulmonary inflammation. In summary, we demonstrated that the pulmonary exposure of ZnONPs stimulated the cytokine-IDO1-AhR loop in the lungs, which has been implied to play roles in immune dysfunctions.

The AhR is involved in the regulation of LoVo cell proliferation through cell cycle-associated proteins.

PubMed

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. © 2016 International Federation for Cell Biology.

Identification and simulation evaluation of an AH-64 helicopter hover math model

NASA Technical Reports Server (NTRS)

Schroeder, J. A.; Watson, D. C.; Tischler, M. B.; Eshow, M. M.

1991-01-01

Frequency-domain parameter-identification techniques were used to develop a hover mathematical model of the AH-64 Apache helicopter from flight data. The unstable AH-64 bare-airframe characteristics without a stability-augmentation system were parameterized in the convectional stability-derivative form. To improve the model's vertical response, a simple transfer-function model approximating the effects of dynamic inflow was developed. Additional subcomponents of the vehicle were also modeled and simulated, such as a basic engine response for hover and the vehicle stick dynamic characteristics. The model, with and without stability augmentation, was then evaluated by AH-64 pilots in a moving-base simulation. It was the opinion of the pilots that the simulation was a satisfactory representation of the aircraft for the tasks of interest. The principal negative comment was that height control was more difficult in the simulation than in the aircraft.

Immuno-detection of dioxins using a recombinant protein of aryl hydrocarbon receptor (AhR) fused with sfGFP.

PubMed

Faiad, Walaa; Hanano, Abdulsamie; Kabakibi, Mohamed Maher; Abbady, Abdul Qader

2016-06-21

Dioxins are one of the most toxic groups of persistent organic pollutants. Their bioaccumulation through the food chain constitutes a potential risk for human health. Upon cell entry, dioxins bind specifically and firmly to the aryl hydrocarbon receptor (AhR), leading to the stimulation of several enzymes responsible for its detoxification. Dioxin/AhR interaction could be exploited as an affordable alternative to a variety of analytical methods for detecting dioxin contamination in the environment. In this work, the ligand binding domain (LBD) of the AhR was cloned downstream a superfolder form of the green fluorescent protein (sfGFP), resulting in the construct pRSET-sfGFP-AhR. High level of expressed sfGFP-AhR fusion protein (50 kDa) was recovered from the inclusion bodies of E. coli by simple solubilization with the Arginine, and purified by affinity chromatography via its N-terminal 6 × His tag. Its purity was confirmed by SDS-PAGE analysis and immunoblotting with anti-His or anti-GFP antibodies. Indirect ELISA revealed the ability of the sfGFP-AhR, but not the sfGFP, to bind to the immobilized dioxin with the possibility to detect such interaction by both its 6 × His and GFP tags,Competitive ELISA showed that anti-dioxin antibody was more sensitive to low dioxin concentrations than sfGFP-AhR. Nevertheless,the detection range of sfGFP-AhR fusion was much wider and the detection limit was of about 10 ppt (parts per trillion) of free dioxin in the tested artificial samples. this highly expressed and functional sfGFP-AhR fusion protein provides a promising molecular tool for detecting and quantifying different congeners of dioxins.

Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria.

PubMed

Korsun, Neli; Angelova, Svetla; Trifonova, Ivelina; Tzotcheva, Iren; Mileva, Sirma; Voleva, Silvia; Georgieva, Irina; Perenovska, Penka

2018-02-01

Influenza viruses are characterised by high variability, which makes them able to cause annual epidemics. The aim of this study is to determine the antigenic and genetic characteristics of influenza viruses circulating in Bulgaria during the 2016/2017 season. The detection and typing/subtyping of influenza viruses were performed using real time RT-PCR. Results of antigenic characterisation, phylogenetic and amino acid sequence analyses of representative influenza strains are presented herein. The 2016/2017 season was characterised by an early start, an exclusive dominance of A(H3N2) viruses accounting for 93 % of total influenza virus detections, and a low circulation of A(H1N1)pdm09 (4.2 %) and type B (2.5 %) viruses. The analysed A(H3N2) viruses belonged to subclades 3C.2a (52 %) and 3C.2a1 (48 %); all studied A(H1N1)pdm09 and B/Victoria-lineage viruses belonged to subclades 6B.1 and 1A, respectively. The amino acid sequence analysis of 56 A(H3N2) isolates revealed the presence of substitutions in 18 positions in haemagglutinin (HA) as compared to the A/Hong Kong/4801/2014 vaccine virus, seven of which occurred in four antigenic sites, together with changes in 23 positions in neuraminidase (NA), and a number of substitutions in internal proteins PB2, PB1, PB1-F2, PA, NP and NS1. Despite the many amino acid substitutions, A(H3N2) viruses remained antigenically similar to the vaccine strain. Substitutions in HA and NA sequences of A(H1N1)pdm09 and B/Victoria-lineage strains were also identified, including in antigenic sites. The results of this study confirm the genetic variability of circulating influenza viruses, particularly A(H3N2), and the need for continued antigenic and molecular surveillance.

Essential oils of culinary herbs and spices display agonist and antagonist activities at human aryl hydrocarbon receptor AhR.

PubMed

Bartoňková, Iveta; Dvořák, Zdeněk

2018-01-01

Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major constituents (>10%) of AhR-active EOs were studied in more detail. We identified AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol, ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones, p-cymene), which account for AhR-mediated activities of EOs of fennel, anise, star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme and oregano. We also show that AhR-mediated effects of some individual constituents of EOs differ from those manifested in mixtures. In conclusion, EOs of culinary herbs and spices are agonists and antagonists of human AhR, implying a potential for food-drug interactions and interference with endocrine pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mortality burden of the 2009 A/H1N1 influenza pandemic in France: comparison to seasonal influenza and the A/H3N2 pandemic.

PubMed

Lemaitre, Magali; Carrat, Fabrice; Rey, Grégoire; Miller, Mark; Simonsen, Lone; Viboud, Cécile

2012-01-01

The mortality burden of the 2009 A/H1N1 pandemic remains unclear in many countries due to delays in reporting of death statistics. We estimate the age- and cause-specific excess mortality impact of the pandemic in France, relative to that of other countries and past epidemic and pandemic seasons. We applied Serfling and Poisson excess mortality approaches to model weekly age- and cause-specific mortality rates from June 1969 through May 2010 in France. Indicators of influenza activity, time trends, and seasonal terms were included in the models. We also reviewed the literature for country-specific estimates of 2009 pandemic excess mortality rates to characterize geographical differences in the burden of this pandemic. The 2009 A/H1N1 pandemic was associated with 1.0 (95% Confidence Intervals (CI) 0.2-1.9) excess respiratory deaths per 100,000 population in France, compared to rates per 100,000 of 44 (95% CI 43-45) for the A/H3N2 pandemic and 2.9 (95% CI 2.3-3.7) for average inter-pandemic seasons. The 2009 A/H1N1 pandemic had a 10.6-fold higher impact than inter-pandemic seasons in people aged 5-24 years and 3.8-fold lower impact among people over 65 years. The 2009 pandemic in France had low mortality impact in most age groups, relative to past influenza seasons, except in school-age children and young adults. The historical A/H3N2 pandemic was associated with much larger mortality impact than the 2009 pandemic, across all age groups and outcomes. Our 2009 pandemic excess mortality estimates for France fall within the range of previous estimates for high-income regions. Based on the analysis of several mortality outcomes and comparison with laboratory-confirmed 2009/H1N1 deaths, we conclude that cardio-respiratory and all-cause mortality lack precision to accurately measure the impact of this pandemic in high-income settings and that use of more specific mortality outcomes is important to obtain reliable age-specific estimates.

Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options.

PubMed

Teschke, Rolf

2018-06-01

Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used. Areas covered: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH. Expert opinion: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.

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.

PubMed

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.

Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014–2015

PubMed Central

Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.

2018-01-01

Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176

A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response

PubMed Central

Talaat, Kawsar R.; Luke, Catherine J.; Khurana, Surender; Manischewitz, Jody; King, Lisa R.; McMahon, Bridget A.; Karron, Ruth A.; Lewis, Kristen D. C.; Qin, Jing; Follmann, Dean A.; Golding, Hana; Neuzil, Kathleen M.; Subbarao, Kanta

2014-01-01

Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV). Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-μg dose of influenza A(H5N1) ISIV. Influenza A(H5N1)– and LAIV-naive subjects received either 1 or 2 doses of ISIV. Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P = .04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV–primed subjects. Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades. Clinical Trials Registration. NCT01109329. PMID:24604819

T-cell expression of AhR inhibits the maintenance of pTreg cells in the gastrointestinal tract in acute GVHD.

PubMed

Dant, Trisha A; Lin, Kaifeng L; Bruce, Danny W; Montgomery, Stephanie A; Kolupaev, Oleg V; Bommiasamy, Hemamalini; Bixby, Lisa M; Woosley, John T; McKinnon, Karen P; Gonzalez, Frank J; Blazar, Bruce R; Vincent, Benjamin G; Coghill, James M; Serody, Jonathan S

2017-07-20

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR -/- T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4 + T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT reg ) cells in the colon of recipients transplanted with AhR -/- T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T reg (iT reg ) cells from naïve CD4 + human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

PubMed

Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am

2018-04-01

A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.

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

PubMed

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

2016-04-12

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

Insights into the Indian Peanut Genotypes for ahFAD2 Gene Polymorphism Regulating Its Oleic and Linoleic Acid Fluxes

PubMed Central

Nawade, Bhagwat; Bosamia, Tejas C.; Thankappan, Radhakrishnan; Rathnakumar, Arulthambi L.; Kumar, Abhay; Dobaria, Jentilal R.; Kundu, Rahul; Mishra, Gyan P.

2016-01-01

In peanut (Arachis hypogaea L.), the customization of fatty acid profile is an evolving area to fulfill the nutritional needs in the modern market. A total of 174 peanut genotypes, including 167 Indian cultivars, 6 advanced breeding lines and “SunOleic95R”—a double mutant line, were investigated using AS-PCRs, CAPS and gene sequencing for the ahFAD2 allele polymorphism, along with its fatty acid compositions. Of these, 80 genotypes were found having substitution (448G>A) mutation only in ahFAD2A gene, while none recorded 1-bp insertion (441_442insA) mutation in ahFAD2B gene. Moreover, 22 wild peanut accessions found lacking both the mutations. Among botanical types, the ahFAD2A mutation was more frequent in ssp. hypogaea (89%) than in ssp. fastigiata (17%). This single allele mutation, found affecting not only oleic to linoleic acid fluxes, but also the composition of other fatty acids in the genotypes studied. Repeated use of a few selected genotypes in the Indian varietal development programs were also eminently reflected in its ahFAD2 allele polymorphism. Absence of known mutations in the wild-relatives indicated the possible origin of these mutations, after the allotetraploidization of cultivated peanut. The SNP analysis of both ahFAD2A and ahFAD2B genes, revealed haplotype diversity of 1.05% and 0.95%, while Ka/Ks ratio of 0.36 and 0.39, respectively, indicating strong purifying selection pressure on these genes. Cluster analysis, using ahFAD2 gene SNPs, showed presence of both mutant and non-mutant genotypes in the same cluster, which might be due the presence of ahFAD2 gene families. This investigation provided insights into the large number of Indian peanut genotypes, covering various aspects related to O/L flux regulation and ahFAD2 gene polymorphism. PMID:27610115

Detection of Avian Influenza A(H7N9) Virus from Live Poultry Markets in Guangzhou, China: A Surveillance Report

PubMed Central

Yuan, Jun; Liu, Hui; Lu, Jianyun; Di, Biao; Xiao, Xincai

2014-01-01

Purpose A virologic surveillance program for A(H7N9) virus was conducted from April 15, 2013 to February 14, 2014 in Guangzhou, aiming to clarify the geographical distribution of A(H7N9) viruses among live poultry markets (LPMs) and poultry farms in Guangzhou. Virological and serological surveys of poultry workers were also conducted to evaluate the risk of poultry-to-human transmission of the A(H7N9) virus. Methods 36 retail LPMs, 6 wholesale LPMs and 8 poultry farms were involved in our surveillance program. About 20 live poultry and environmental samples were obtained from each surveillance site at every sampling time. Different environmental samples were collected to represent different poultry-related work activities. RT-PCR and virus culture were performed to identify the A(H7N9) virus. Hemagglutinin inhibition assay and RT-PCR were conducted to detect possible A(H7N9) infection among poultry workers. Results A total of 8900 live poultry and environmental samples were collected, of which 131(1.5%) were tested positive for A(H7N9) virus. 44.4% (16/36) of retail LPMs and 50.0% (3/6) of wholesale LPMs were confirmed to be contaminated. No positive samples was detected from poultry farms. A significant higher positive sample rate was found in environmental samples related to poultry selling (2.6%) and slaughtering (2.4%), compared to poultry holding (0.9%). Correspondingly, A(H7N9) viruses were isolated most frequently from slaughter zone. In addition, 316 poultry workers associated with the 19 contaminated-LPMs were recruited and a low seroprevalence (1.6%) of antibody against A(H7N9) virus was detected. An asymptomatic A(H7N9) infection was also identified by RT-PCR. Conclusions Our study highlights the importance of conducting effective surveillance for A(H7N9) virus and provides evidence to support the assumption that slaughtering is the key process for the propagation of A(H7N9) virus in retail LPMs. Moreover, the ability of A(H7N9) virus to cross species

Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017.

PubMed

Zhou, Lei; Tan, Yi; Kang, Min; Liu, Fuqiang; Ren, Ruiqi; Wang, Yali; Chen, Tao; Yang, Yiping; Li, Chao; Wu, Jie; Zhang, Hengjiao; Li, Dan; Greene, Carolyn M; Zhou, Suizan; Iuliano, A Danielle; Havers, Fiona; Ni, Daxin; Wang, Dayan; Feng, Zijian; Uyeki, Timothy M; Li, Qun

2017-08-01

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity.

PubMed

Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cecile; Simonsen, Lone; Grajales Muñiz, Concepcion; Rascón Pacheco, Ramón Alberto; González León, Margot; Borja Aburto, Víctor Hugo

2012-02-24

A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time. We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset. A total of 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The reproduction number of the

Novel roles for AhR and ARNT in the regulation of alcohol dehydrogenases in human hepatic cells.

PubMed

Attignon, Eléonore A; Leblanc, Alix F; Le-Grand, Béatrice; Duval, Caroline; Aggerbeck, Martine; Rouach, Hélène; Blanc, Etienne B

2017-01-01

The mechanisms by which pollutants participate in the development of diverse pathologies are not completely understood. The pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the AhR (aryl hydrocarbon receptor) signaling pathway. We previously showed that TCDD (25 nM, 30 h) decreased the expression of several alcohol metabolism enzymes (cytochrome P450 2E1, alcohol dehydrogenases ADH1, 4 and 6) in differentiated human hepatic cells (HepaRG). Here, we show that, as rapidly as 8 h after treatment (25 nM TCDD) ADH expression decreased 40 % (p < 0.05). ADH1 and 4 protein levels decreased 40 and 27 %, respectively (p < 0.05), after 72 h (25 nM TCDD). The protein half-lives were not modified by TCDD which suggests transcriptional regulation of expression. The AhR antagonist CH-223191 or AhR siRNA reduced the inhibitory effect of 25 nM TCDD on ADH1A, 4 and 6 expression 50-100 % (p < 0.05). The genomic pathway (via the AhR/ARNT complex) and not the non-genomic pathway involving c-SRC mediated these effects. Other AhR ligands (3-methylcholanthrene and PCB 126) decreased ADH1B, 4 and 6 mRNAs by more than 78 and 55 %, respectively (p < 0.01). TCDD also regulated the expression of ADH4 in the HepG2 human hepatic cell line, in primary human hepatocytes and in C57BL/6J mouse liver. In conclusion, activation of the AhR/ARNT signaling pathway by AhR ligands represents a novel mechanism for regulating the expression of ADHs. These effects may be implicated in the toxicity of AhR ligands as well as in the alteration of ethanol or retinol metabolism and may be associated further with higher risk of liver diseases or/and alcohol abuse disorders.

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

PubMed

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.

Correlations between A/H1N1 influenza and acute cellular rejection in liver transplantation patients.

PubMed

Stucchi, R S B; Boin, I F S F; Angerami, R Nogueira; Sinckoc, V; Sa, F Cesar; Seva-Pereira, T; Escanhoela, C A Fazzio

2010-12-01

Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes. Copyright © 2010 Elsevier Inc. All rights reserved.

Mild Illness in Avian Influenza A(H7N9) Virus–Infected Poultry Worker, Huzhou, China, April 2013

PubMed Central

Lv, Huakun; Han, Jiankang; Zhang, Peng; Lu, Ye; Wen, Dong; Cai, Jian; Liu, Shelan; Sun, Jimin; Yu, Zhao; Zhang, Heng; Gong, Zhenyu; Chen, Enfu

2013-01-01

During April 2013 in China, mild respiratory symptoms developed in 1/61 workers who had culled influenza A(H7N9) virus–infected poultry. Laboratory testing confirmed A(H7N9) infection in the worker and showed that the virus persisted longer in sputum than pharyngeal swab samples. Pharyngeal swab samples from the other workers were negative for A(H7N9) virus. PMID:24209963

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

Potentially-toxic and essential elements profile of AH1N1 patients in Mexico City

PubMed Central

Moya, Mireya; Bautista, Edgar G.; Velázquez-González, Antonio; Vázquez-Gutiérrez, Felipe; Tzintzun, Guadalupe; García-Arreola, María Elena; Castillejos, Manuel; Hernández, Andrés

2013-01-01

During spring of 2009, a new influenza virus AH1N1 spread in the world causing acute respiratory illness and death, resulting in the first influenza pandemic since 1968. Blood levels of potentially-toxic and essential elements of 40 pneumonia and confirmed AH1N1 were evaluated against two different groups of controls, both not infected with the pandemic strain. Significant concentrations of potentially-toxic elements (lead, mercury, cadmium, chromium, arsenic) along with deficiency of selenium or increased Zn/Cu ratios characterized AH1N1 cases under study when evaluated versus controlled cases. Deficiency of selenium is progressively observed from controls I (influenza like illness) through controls II (pneumonia) and finally pneumonia -AH1N1 infected patients. Cases with blood Se levels greater than the recommended for an optimal cut-off to activate glutathione peroxidase (12.5 μg/dL) recovered from illness and survived. Evaluation of this essential element in critical pneumonia patients at the National Institutes is under evaluation as a clinical trial. PMID:23422930

Pandemic influenza A(H1N1)pdm09: An unrecognized cause of mortality in children in Pakistan

PubMed Central

ALI, SYED ASAD; AZIZ, FATIMA; AKHTAR, NIDA; QURESHI, SHAHIDA; EDWARDS, KATHRYN; ZAIDI, ANITA

2016-01-01

The role of influenza virus as a cause of child mortality in South Asia is under-recognized. We aimed to determine the incidence and case fatality rate of influenza A(H1N1)pdm09 infections in hospitalized children in Karachi, Pakistan. Children less than 5 y old admitted with respiratory illnesses to the Aga Khan University Hospital, Karachi, from 17 August 2009 to 16 September 2011, were tested for influenza A(H1N1)pdm09 using a real-time reverse transcriptase polymerase chain reaction. Out of 2650 children less than 5 y old admitted with a respiratory illness during the study period, 812 (31%) were enrolled. Influenza A(H1N1)pdm09 virus was detected in 27 (3.3%) children. There were 4 deaths in children who tested positive for influenza A(H1N1)pdm09 (case fatality rate of 15%). Children with influenza A(H1N1)pdm09 were 5 times more likely to be admitted or transferred to the intensive care unit, 5.5 times more likely to be intubated, and 12.9 times more likely to die as compared to children testing negative for influenza A(H1N1)pdm09. PMID:23826795

Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin

PubMed Central

Magiatis, Prokopios; Pappas, Periklis; Gaitanis, George; Mexia, Nikitia; Melliou, Eleni; Galanou, Maria; Vlachos, Christophoros; Stathopoulou, Konstantina; Skaltsounis, Alexios Leandros; Marselos, Marios; Velegraki, Aristea; Denison, Michael S.; Bassukas, Ioannis D.

2013-01-01

Malassezia yeasts are commensal microorganisms which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia associated diseases demonstrated 10–1000 fold higher AhR activating capacity than control skin extracts. LC/MS/MS analysis of the patients’ extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9/12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture-extracts and pure metabolites in HaCaT cells by Reverse Transcriptase Real-Time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1 and AhRR. Indirubin and FICZ activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared to the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. PMID:23448877

Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin.

PubMed

Magiatis, Prokopios; Pappas, Periklis; Gaitanis, George; Mexia, Nikitia; Melliou, Eleni; Galanou, Maria; Vlachos, Christophoros; Stathopoulou, Konstantina; Skaltsounis, Alexios Leandros; Marselos, Marios; Velegraki, Aristea; Denison, Michael S; Bassukas, Ioannis D

2013-08-01

Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10- to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients' extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin- and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development.

The 50Ah NiH2 cell life test results

NASA Technical Reports Server (NTRS)

Jamin, Thierry; Puig, Olivier

1992-01-01

Information is given in viewgraph form for the 50 AhNiH2 cell life test results. Information is given on pressure vessel design, electrochemical/stack design, cell electrical characteristics, and cell life test results.

Transmission of pandemic A/H1N1 2009 influenza on passenger aircraft: retrospective cohort study

PubMed Central

Thornley, Craig N; Mills, Clair; Roberts, Sally; Perera, Shanika; Peters, Julia; Kelso, Anne; Barr, Ian; Wilson, Nick

2010-01-01

Objectives To assess the risk of transmission of pandemic A/H1N1 2009 influenza (pandemic A/H1N1) from an infected high school group to other passengers on an airline flight and the effectiveness of screening and follow-up of exposed passengers. Design Retrospective cohort investigation using a questionnaire administered to passengers and laboratory investigation of those with symptoms. Setting Auckland, New Zealand, with national and international follow-up of passengers. Participants Passengers seated in the rear section of a Boeing 747-400 long haul flight that arrived on 25 April 2009, including a group of 24 students and teachers and 97 (out of 102) other passengers in the same section of the plane who agreed to be interviewed. Main outcome measures Laboratory confirmed pandemic A/H1N1 infection in susceptible passengers within 3.2 days of arrival; sensitivity and specificity of influenza symptoms for confirmed infection; and completeness and timeliness of contact tracing. Results Nine members of the school group were laboratory confirmed cases of pandemic A/H1N1 infection and had symptoms during the flight. Two other passengers developed confirmed pandemic A/H1N1 infection, 12 and 48 hours after the flight. They reported no other potential sources of infection. Their seating was within two rows of infected passengers, implying a risk of infection of about 3.5% for the 57 passengers in those rows. All but one of the confirmed pandemic A/H1N1 infected travellers reported cough, but more complex definitions of influenza cases had relatively low sensitivity. Rigorous follow-up by public health workers located 93% of passengers, but only 52% were contacted within 72 hours of arrival. Conclusions A low but measurable risk of transmission of pandemic A/H1N1 exists during modern commercial air travel. This risk is concentrated close to infected passengers with symptoms. Follow-up and screening of exposed passengers is slow and difficult once they have left the

Transmission of pandemic A/H1N1 2009 influenza on passenger aircraft: retrospective cohort study.

PubMed

Baker, Michael G; Thornley, Craig N; Mills, Clair; Roberts, Sally; Perera, Shanika; Peters, Julia; Kelso, Anne; Barr, Ian; Wilson, Nick

2010-05-21

To assess the risk of transmission of pandemic A/H1N1 2009 influenza (pandemic A/H1N1) from an infected high school group to other passengers on an airline flight and the effectiveness of screening and follow-up of exposed passengers. Retrospective cohort investigation using a questionnaire administered to passengers and laboratory investigation of those with symptoms. Auckland, New Zealand, with national and international follow-up of passengers. Passengers seated in the rear section of a Boeing 747-400 long haul flight that arrived on 25 April 2009, including a group of 24 students and teachers and 97 (out of 102) other passengers in the same section of the plane who agreed to be interviewed. Laboratory confirmed pandemic A/H1N1 infection in susceptible passengers within 3.2 days of arrival; sensitivity and specificity of influenza symptoms for confirmed infection; and completeness and timeliness of contact tracing. Nine members of the school group were laboratory confirmed cases of pandemic A/H1N1 infection and had symptoms during the flight. Two other passengers developed confirmed pandemic A/H1N1 infection, 12 and 48 hours after the flight. They reported no other potential sources of infection. Their seating was within two rows of infected passengers, implying a risk of infection of about 3.5% for the 57 passengers in those rows. All but one of the confirmed pandemic A/H1N1 infected travellers reported cough, but more complex definitions of influenza cases had relatively low sensitivity. Rigorous follow-up by public health workers located 93% of passengers, but only 52% were contacted within 72 hours of arrival. A low but measurable risk of transmission of pandemic A/H1N1 exists during modern commercial air travel. This risk is concentrated close to infected passengers with symptoms. Follow-up and screening of exposed passengers is slow and difficult once they have left the airport.

Rewarding and reinforcing effects of 4-chloro-2,5-dimethoxyamphetamine and AH-7921 in rodents.

PubMed

Cha, Hye Jin; Jeon, Seo Young; Jang, Hwa Jin; Shin, Jisoon; Kim, Young-Hoon; Suh, Soo Kyung

2018-05-29

New psychoactive substances (NPSs), i.e., newly designed substances with chemical residues that are slightly different from those of known psychoactive substances, have been emerging since the late 2000s, and social problems related to the use of these substances are increasing globally. Two such NPSs are 4-chloro-2,5-dimethoxyamphetamine (DOC), a psychedelic substance that is structurally related to amphetamine, and AH-7921, an opioid analgesic that is used for recreational purposes and has a potency similar to that of morphine. Currently, scientific evidence for the dependence liability or toxicity of NPSs is lacking. Therefore, in this study, we performed animal behavioral tests to evaluate the dependence liability of DOC and AH-7921. The rewarding and reinforcing effects of DOC and AH-7921 were evaluated using the conditioned place preference (CPP) paradigm in mice and the self-administration (SA) procedure in rats. Both DOC and AH-7921 increased the preference for the drug-paired compartment in the CPP test at a dose of 0.3 mg/kg and increased the number of responses to the active lever in the SA test at 0.01 mg/(kg·infusion). Collectively, the data suggest that DOC and AH-7921 may have both rewarding and reinforcing effects. Further studies are needed to confirm the reinforcing effects in broader dose ranges with various schedules. Copyright © 2018 Elsevier B.V. All rights reserved.

The Airbag as a Supplement to Standard Restraint Systems in the AH-1 and AH-64 Attack Helicopters and Its Role in Reducing Head Strikes of the Copilot/ Gunner. Volume 1

DTIC Science & Technology

1991-01-01

shelf and locally available automotive airbag system was selected for the tests. The system was a driver’s side airbag designed by Honda Motor Company...allowance for hardware redesign or modifi- cation. Despite these limitations, the study succeeded in demonstrating a problem exists and a supplemental airbag ...JSAARL Repqrt No. 91-8 AD-A233 349 Volume’ I(3 The Airbag as a Supplement to Standard Restraint Systems in the AH-1 and AH-64 Attack Helicopters and

Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India

PubMed Central

Mukherjee, Anupam; Nayak, Mukti Kant; Dutta, Shanta; Panda, Samiran; Satpathi, Biswa Ranjan; Chawla-Sarkar, Mamta

2016-01-01

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014–2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains. PMID:27997573

Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination.

PubMed

Fell, Deshayne B; Wilson, Kumanan; Ducharme, Robin; Hawken, Steven; Sprague, Ann E; Kwong, Jeffrey C; Smith, Graeme; Wen, Shi Wu; Walker, Mark C

2016-01-01

Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia. We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores. Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27-3.76 and 3.60, 95% CI: 2.51-5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period. We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited.

Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India.

PubMed

Mukherjee, Anupam; Nayak, Mukti Kant; Dutta, Shanta; Panda, Samiran; Satpathi, Biswa Ranjan; Chawla-Sarkar, Mamta

2016-01-01

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014-2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains.

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

PubMed Central

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

Long life 80Ah standard IPV NiH2 battery cell

NASA Technical Reports Server (NTRS)

Armantrout, Jon D.; Waller, J. S.

1995-01-01

A standard Nickel-Hydrogen (NiH2) Individual Pressure Vessel (IPV) battery cell is needed to meet future low cost, high performance mission requirements for NASA, military, and civil space programs. A common or standard cell design has evolved from the heritage of HST, Milstar, and other Air Force Mantech cell designs with substantial flight experience, while incorporating some of the historical COMSAT cell design features described in a previous NASA publication. Key features include slurry process nickel electrodes having high strength, long life and high yield (lower cost), and dual layer zircar separators for improved KOH retention, uniformality, and longer life. The cell design will have a zirconium oxide wall wick inside the pressure vessel to redistribute electrolyte and extend life. The slurry electrode will be 35 mils thick to take advantage of qualified cell mechanical configurations and proven assembly and activation techniques developed by Eagle Picher Industries (EPI) for the Hubble Space Telescope (HST) RNH-90-3 and 'Generic HST' RNH-90-5 cell designs with back-to-back nickel electrodes produced by the dry sinter process. The 80Ah common cell design can be scaled to meet capacity requirements from 60Ah to 100Ah. Producibility, commonality, and long life performance will be enhanced with the robust cell design described herein.

TCDD, FICZ, and Other High Affinity AhR Ligands Dose-Dependently Determine the Fate of CD4+ T Cell Differentiation.

PubMed

Ehrlich, Allison K; Pennington, Jamie M; Bisson, William H; Kolluri, Siva K; Kerkvliet, Nancy I

2018-02-01

FICZ and TCDD, two high-affinity AhR ligands, are reported to have opposite effects on T cell differentiation with TCDD inducing regulatory T cells and FICZ inducing Th17 cells. This dichotomy has been attributed to ligand-intrinsic differences in AhR activation, although differences in sensitivity to metabolism complicate the issue. TCDD is resistant to AhR-induced metabolism and produces sustained AhR activation following a single dose in the μg/kg range, whereas FICZ is rapidly metabolized and AhR activation is transient. Nonetheless, prior studies comparing FICZ with TCDD have generally used the same 10-50 μg/kg dose range, and thus the two ligands would not equivalently activate AhR. We hypothesized that high-affinity AhR ligands can promote CD4+ T cell differentiation into both Th17 cells and Tregs, with fate depending on the extent and duration of AhR activation. We compared the immunosuppressive effects of TCDD and FICZ, along with two other rapidly metabolized ligands (ITE and 11-Cl-BBQ) in an acute alloresponse mouse model. The dose and timing of administration of each ligand was optimized for TCDD-equivalent Cyp1a1 induction. When optimized, all of the ligands suppressed the alloresponse in conjunction with the induction of Foxp3- Tr1 cells on day 2 and the expansion of natural Foxp3+ Tregs on day 10. In contrast, a low dose of FICZ induced transient expression of Cyp1a1 and did not induce Tregs or suppress the alloresponse but enhanced IL-17 production. Interestingly, low doses of the other ligands, including TCDD, also increased IL-17 production on day 10. These findings support the conclusion that the dose and the duration of AhR activation by high-affinity AhR ligands are the primary factors driving the fate of T cell differentiation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals.

PubMed

Desheva, Yulia; Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna

2018-01-01

The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses.

Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals

PubMed Central

Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna

2018-01-01

The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses. PMID:29742168

The Influence of the Autoimmunity-Associated Ancestral HLA Haplotype AH8.1 on the Human Gut Microbiota: A Cross-Sectional Study

PubMed Central

Qin, Bingcai; Anmarkrud, Jarl Andreas; Holm, Kristian; Franke, Andre; Lie, Benedicte A.; Karlsen, Tom H.

2015-01-01

Multiple immune-related genes are encoded in the HLA complex on chromosome 6p21. The 8.1 ancestral haplotype (AH8.1) include the classical HLA alleles HLA-B*08:01 and HLA-DRB1*03:01, and has been associated with a large number of autoimmune diseases, but the underlying mechanisms for this association are largely unknown. Given the recently established links between the gut microbiota and inflammatory diseases, we hypothesized that the AH8.1 influences the host gut microbial community composition. To study this further, healthy individuals were selected from the Norwegian Bone Marrow Donor Registry and categorized as either I. AH8.1 homozygote (n=34), II. AH8.1 heterozygote (n=38), III. Non AH8.1 heterozygote or IV. HLA-DRB1 homozygote but non AH8.1 (n=15). Bacterial DNA from stool samples were subjected to sequencing of the V3–V5 region of the 16S rRNA gene on the 454 Life Sciences platform and data analyzed using Mothur and QIIME. The results showed that the abundances of different taxa were highly variable within all pre-defined AH8.1 genotype groups. Using univariate non-parametric statistics, there were no differences regarding alpha or beta diversity between AH8.1 carriers (categories I and II) and non-carriers (categories III and IV), however four different taxa (Prevotellaceae, Clostridium XVIII, Coprococcus, Enterorhabdus) had nominally significant lower abundances in AH8.1 carriers than non-carriers. After including possible confounders in a multivariate linear regression, only the two latter genera remained significantly associated. In conclusion, the overall contribution of the AH8.1 haplotype to the variation in gut microbiota profile of stool in the present study was small. PMID:26207384

Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction.

PubMed

Park, Wook-Ha; Jun, Dae Won; Kim, Jin Taek; Jeong, Jae Hoon; Park, Hyokeun; Chang, Yoon-Seok; Park, Kyong Soo; Lee, Hong Kyu; Pak, Youngmi Kim

2013-01-01

Serum concentrations of environmental pollutants have been positively correlated with diabetes and metabolic syndrome in epidemiologic studies. In turn, abnormal mitochondrial function has been associated with the diseases. The relationships between these variables, however, have not been studied. We developed novel cell-based aryl hydrocarbon receptor (AhR) agonist bioassay system without solvent extraction process and analyzed whether low-dose circulating AhR ligands in human serum are associated with parameters of metabolic syndrome and mitochondrial function. Serum AhR ligand activities were measured as serum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (sTCDDeq) in pM using 10 μL human sera from 97 Korean participants (47 with glucose intolerance and 50 matched controls, average age of 46.6 ± 9.9 years, 53 male and 45 female). sTCDDeq were higher in participants with glucose intolerance than normal controls and were positively associated (P < 0.01) with obesity, blood pressure, serum triglyceride, and fasting glucose, but not with HDL-cholesterol. Body mass index was in a positive linear relationship with serum AhR ligands in healthy participants. When myoblast cells were incubated with human sera, ATP generating power of mitochondria became impaired in an AhR ligand concentration-dependent manner. Our results support that circulating AhR ligands may directly reduce mitochondrial function in tissues, leading to weight gain, glucose intolerance, and metabolic syndrome. Our rapid cell-based assay using minute volume of human serum may provide one of the best monitoring systems for circulating AhR ligands, good clinical biomarkers for the progress of disease and therapeutic efficacy. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Hyperascyrones A-H, polyprenylated spirocyclic acylphloroglucinol derivatives from Hypericum ascyron Linn.

PubMed

Zhu, Hucheng; Chen, Chunmei; Liu, Junjun; Sun, Bin; Wei, Guangzheng; Li, Yan; Zhang, Jinwen; Yao, Guangmin; Luo, Zengwei; Xue, Yongbo; Zhang, Yonghui

2015-07-01

Eight polyprenylated spirocyclic acylphloroglucinol derivatives (PSAPs), hyperascyrones A-H, were isolated from the aerial parts of Hypericum ascyron Linn., together with six known analogs. Their structures were established by spectroscopic analyses including HRESIMS, 1D and 2D NMR, and their absolute configurations were determined by electronic circular dichroism calculations (ECD, Gaussian 09). Structures of previously reported tomoeones C, D, G, and H were revised. Hyperascyrones A-H were evaluated for their cytotoxic and anti-HIV-1 activities, with hyperascyrones C and G exhibiting significant cytotoxicities against HL-60 cell lines with IC50 values of 4.22 and 8.36 μM, respectively. In addition, the chemotaxonomic significance of these compounds was also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011.

PubMed

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi; Mai, Le Quynh

2014-01-01

Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. The overall seroprevalence was 6.1% (95% confidence interval: 4.6-8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian-human transmission of influenza A(H5N1) in Viet Nam.

A comparative evaluation of antimicrobial efficacy and flow properties for Epiphany, Guttaflow and AH-Plus sealer.

PubMed

Nawal, R R; Parande, M; Sehgal, R; Naik, A; Rao, N R

2011-04-01

To test the antimicrobial efficacy and flow properties of Guttaflow, Epiphany sealer and AH-Plus sealer. With the use of Enterococcus faecalis ATCC 29212 as a test organism, both the agar diffusion test (ADT) and direct contact test (DCT) were performed. For DCT, sealers were mixed and placed over the bottom of sterile screw-capped test tubes. A 50 μL bacterial suspension was placed on the tested material samples. Bacteria were allowed to directly come in contact with the sealers for 1 h at 37 °C in one group and for 24 h in the other group. The suspensions were then diluted and inoculated over blood agar plates, and bacterial colony counts were determined with the use of a digital colony counter. The data in both 1- and 24-h groups were individually analysed using repeated measures ANOVA. Kruskal Wallis tests were further used to obtain comparison between 1- and 24-h results for all three sealers. In the flow assay, the sealers were placed between two glass slides, and a weight of 500 g was placed on the top of the glass. The diameters of the formed discs were recorded. For both the ADT and DCT tests, Epiphany and AH-Plus sealer reduced the bacterial counts significantly (P = 0.000). Epiphany produced a greater reduction in bacterial counts when compared to AH-Plus in both the tests (P = 0.000). Guttaflow paste failed to show any antibacterial activity in both ADT & DCT. According to the flow test, all root canal sealers flowed; Epiphany sealer had the maximum flow under the given conditions, followed by AH-Plus sealer and Guttaflow paste. Antimicrobial activity of the sealers was greatest for Epiphany followed by AH-Plus sealer and Guttaflow. Epiphany sealer had the maximum flow followed by AH-Plus sealer and Guttaflow. © 2010 International Endodontic Journal.

Assessment of EchoMRI-AH versus dual-energy X-ray absorptiometry to measure human body composition.

PubMed

Galgani, J E; Smith, S R; Ravussin, E

2011-09-01

The sensitivity to detect small changes in body composition (fat mass and fat-free mass) largely depends on the precision of the instrument. We compared EchoMRI-AH and dual-energy X-ray absorptiometry (DXA) (Hologic QDR-4500A) for estimating fat mass in 301 volunteers. Body composition was evaluated in 136 males and 165 females with a large range of body mass index (BMI) (19-49 kg m(-2)) and age (19-91 years old) using DXA and EchoMRI-AH. In a subsample of 13 lean (BMI=19-25 kg m(-2)) and 21 overweight/obese (BMI>25 kg m(-2)) individuals, within-subject precision was evaluated from repeated measurements taken within 1 h (n=3) and 1 week apart (mean of three measurements taken on each day). Using Bland-Altman analysis, we compared the mean of the fat mass measurements versus the difference in fat mass measured by both instruments. We found that EchoMRI-AH quantified larger amount of fat versus DXA in non-obese (BMI<30 kg m(-2) (1.1 kg, 95% confidence interval (CI(95)):-3.7 to 6.0)) and obese (BMI ≥ 30 kg m(-2) (4.2 kg, CI(95):-1.4 to 9.8)) participants. Within-subject precision (coefficient of variation, %) in fat mass measured within 1 h was remarkably better when measured by EchoMRI-AH than DXA (<0.5 versus <1.5%, respectively; P<0.001). However, 1-week apart within-subject variability showed similar values for both instruments (<2.2%; P=0.15). EchoMRI-AH yielded greater fat mass values when compared with DXA (Hologic QDR-4500A), particularly in fatter subjects. EchoMRI-AH and DXA showed similar 1-week apart precision when fat mass was measured both in lean and overweight/obese individuals.

Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus, Guangdong, China

PubMed Central

Wu, Jie; Lu, Jing; Faria, Nuno R.; Zeng, Xianqiao; Song, Yingchao; Zou, Lirong; Yi, Lina; Liang, Lijun; Ni, Hanzhong; Kang, Min; Zhang, Xin; Huang, Guofeng; Zhong, Haojie; Bowden, Thomas A.; Raghwani, Jayna; He, Jianfeng; He, Xiang; Lin, Jinyan; Koopmans, Marion; Pybus, Oliver G.

2016-01-01

Since March 2013, three waves of human infection with avian influenza A(H7N9) virus have been detected in China. To investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in Guangdong during 2013–2015. We observed a geographic shift of human A(H7N9) infections from the second to the third waves. Live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated that the third-wave outbreaks in central Guangdong most likely resulted from local virus persistence rather than introduction from elsewhere. Although the number of clinical cases in humans declined by 35% from the second to the third waves, the genetic diversity of third-wave viruses in Guangdong increased. Our results highlight the epidemic risk to a region reporting comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry market interventions cannot completely halt A(H7N9) virus persistence and dissemination. PMID:27869613

The Fifth Influenza A(H7N9) Epidemic: A Family Cluster of Infection in Suzhou City of China, 2016.

PubMed

Wang, Jiajia; Su, Nan; Dong, Zefeng; Liu, Cheng; Cui, Pengwei; Huang, Jian-An; Chen, Cheng; Zhu, Yehan; Chen, Liling

2018-05-05

Influenza A(H7N9) virus is known for its high pathogenicity in human. A family cluster of influenza A(H7N9) virus infection was identified in Suzhou, China. This study aimed to investigate the possibility of human-to-human transmission of the virus and examine the virologic features of this family cluster. The clinical and epidemiologic data of two patients in the family cluster of influenza A(H7N9) virus infection were collected. Viral RNA in samples derived from the two patients, their close contacts, and the environments with likely influenza A(H7N9) virus transmission were tested by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay. Hemagglutination inhibition (HI) assay was used to detect virus-specific antibodies. Genetic sequencing and phylogenetic analysis were also performed. The index patient (Case 1), a 66-year old man, was virologically diagnosed of influenza A(H7N9) virus infection 12days after experiencing influenza-like symptoms, then died of multi-organ failure. His 39-year old daughter (Case 2), denying any other exposure to influenza A(H7N9) virus, became infected with influenza A(H7N9) virus following taking care of her father during his illness. Sequencing viral genomes isolated from the two patients showed nearly identical nucleotide sequence, and genetically resembled the viral genome isolated from a chicken in the wet market where the index patient once visited. All three influenza A(H7N9) viruses shared S138A, G186V, Q226L mutations in HA (H3) protein and a single basic amino acid (PEIPKGR↓G) at the cleavage site. Human-to-human transmission of influenza A(H7N9) virus most likely occurred in this household. The three-amino-acid mutations in HA protein were discovered in this study, which might have increased the binding affinity of influenza A(H7N9) virus to the receptor on trachea epithelial cells to facilitate viral transmission among humans. Copyright © 2018. Published by Elsevier Ltd.

Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013.

PubMed

Khodadad, Nastaran; Moattari, Afagh; Shamsi Shahr Abadi, Mahmoud; Kadivar, Mohammad Rahim; Sarvari, Jamal; Tavakoli, Forough; Pirbonyeh, Neda; Emami, Amir

2015-08-01

Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene. This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Throat swab samples were collected from 200 patients with influenza-like disease from December 2012 until February 2013. A total of 77 influenza A(H1N1)pdm09 positive strains were identified by real-time polymerase chain reaction (PCR). Oseltamivir resistance was detected using quantal assay and nested-PCR method. The NA gene sequencing was conducted to detect oseltamivir-resistant mutants and establish the phylogeny of the prevalent influenza variants. Our results revealed that A(H1N1)pdm09 viruses present in these samples were susceptible to oseltamivir, and contained 5 site specific mutations (V13G, V106I, V241I, N248D, and N369K) in NA gene. These mutations correlated with increasing expression and enzymatic activity of NA protein in the influenza A(H1N1)pdm09 viruses, which were closely related to a main influenza A(H1N1)pdm09 cluster isolated around the world. A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir.

Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Mexico from 2003 to 2012

PubMed Central

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

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

PubMed Central

Zhu, Conghui; Xie, Qunhui; Zhao, Bin

2014-01-01

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

Circulating levels of miR-150 are associated with poorer outcomes of A/H1N1 infection.

PubMed

Morán, Juan; Ramírez-Martínez, Gustavo; Jiménez-Alvarez, Luis; Cruz, Alfredo; Pérez-Patrigeon, Santiago; Hidalgo, Alfredo; Orozco, Lorena; Martínez, Angélica; Padilla-Noriega, Luis; Avila-Moreno, Federico; Cabello, Carlos; Granados, Julio; Ortíz-Quintero, Blanca; Ramírez-Venegas, Alejandra; Ruíz-Palacios, Guillermo M; Zlotnik, Albert; Merino, Enrique; Zúñiga, Joaquín

2015-10-01

Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically ill patients. The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression. Copyright © 2015 Elsevier Inc. All rights reserved.

Oseltamivir-resistant influenza A(H1N1)pdm09 virus associated with high case fatality, India 2015.

PubMed

Tandel, Kundan; Sharma, Shashi; Dash, Paban Kumar; Parida, ManMohan

2018-05-01

Influenza A viruses has been associated with severe global pandemics of high morbidity and mortality with devastating impact on human health and global economy. India witnessed a major outbreak of influenza A(H1N1)pdm09 in 2015. This study comprises detailed investigation of cases died of influenza A(H1N1)pdm09 virus infection during explosive outbreak of 2015, in central part of India. To find out presence of drug resistant virus among patients who died of influenza A(H1N1)pdm09 virus infection and to find out presence of other mutations contributing to the morbidity and mortality. Twenty-two patients having confirmed influenza A(H1N1)pdm09 infection and subsequently died of this infection along with 20 non fatal cases with influenza A(H1N1)pdm09 infection were included in the study. Samples were investigated through RT-PCR/RFLP analysis, followed by nucleotide cycle sequencing of whole NA gene for detection of H275Y amino acid substitution in NA gene responsible for oseltamivir drug resistance. Out of 22 fatal cases, 6 (27.27%) were found to harbor oseltamivir resistant virus strains, whereas the H275Y mutation was not observed among the 20 non fatal cases. Amino acid substitution analysis of complete NA gene revealed V241I, N369K, N386K substitution in all strains playing synergistic role in oseltamivir drug resistance. High morbidity and mortality associated with influenza A(H1N1)pdm09 viruses can be explained by presence of drug resistant strains circulating in this outbreak. Presence of Oseltamivir resistant influenza A(H1N1)pdm09 viruses is a cause of great concern and warrants continuous screening for the circulation of drug resistant strains. © 2017 Wiley Periodicals, Inc.

Epidemiology of human infections with highly pathogenic avian influenza A(H7N9) virus in Guangdong, 2016 to 2017.

PubMed

Kang, Min; Lau, Eric H Y; Guan, Wenda; Yang, Yuwei; Song, Tie; Cowling, Benjamin J; Wu, Jie; Peiris, Malik; He, Jianfeng; Mok, Chris Ka Pun

2017-07-06

We describe the epidemiology of highly pathogenic avian influenza (HPAI) A(H7N9) based on poultry market environmental surveillance and laboratory-confirmed human cases (n = 9) in Guangdong, China. We also compare the epidemiology between human cases of high- and low-pathogenic avian influenza A(H7N9) (n = 51) in Guangdong. Case fatality and severity were similar. Touching sick or dead poultry was the most important risk factor for HPAI A(H7N9) infections and should be highlighted for the control of future influenza A(H7N9) epidemics. This article is copyright of The Authors, 2017.

AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod-induced psoriasis mouse model.

PubMed

Cochez, Perrine M; Michiels, Camille; Hendrickx, Emilie; Van Belle, Astrid B; Lemaire, Muriel M; Dauguet, Nicolas; Warnier, Guy; de Heusch, Magali; Togbe, Dieudonnée; Ryffel, Bernhard; Coulie, Pierre G; Renauld, Jean-Christophe; Dumoutier, Laure

2016-06-01

IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

2011-01-01

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

Identification of Amino Acid Changes That May Have Been Critical for the Genesis of A(H7N9) Influenza Viruses

PubMed Central

Neumann, Gabriele; Macken, Catherine A.

2014-01-01

ABSTRACT Novel influenza A viruses of the H7N9 subtype [A(H7N9)] emerged in the spring of 2013 in China and had infected 163 people as of 10 January 2014; 50 of them died of the severe respiratory infection caused by these viruses. Phylogenetic studies have indicated that the novel A(H7N9) viruses emerged from reassortment of H7, N9, and H9N2 viruses. Inspections of protein sequences from A(H7N9) viruses and their immediate predecessors revealed several amino acid changes in A(H7N9) viruses that may have facilitated transmission and replication in the novel host. Since mutations that occurred more ancestrally may also have contributed to the genesis of A(H7N9) viruses, we inferred historical evolutionary events leading to the novel viruses. We identified a number of amino acid changes on the evolutionary path to A(H7N9) viruses, including substitutions that may be associated with host range, replicative ability, and/or host responses to infection. The biological significance of these amino acid changes can be tested in future studies. IMPORTANCE The novel influenza A viruses of the H7N9 subtype [A(H7N9)], which first emerged in the spring of 2013, cause severe respiratory infections in humans. Here, we performed a comprehensive evolutionary analysis of the progenitors of A(H7N9) viruses to identify amino acid changes that may have been critical for the emergence of A(H7N9) viruses and their ability to infect humans. We provide a list of potentially important amino acid changes that can be tested for their significance for the influenza virus host range, replicative ability, and/or host responses to infection. PMID:24522919

Contextual generalized trust and immunization against the 2009 A(H1N1) pandemic in the American states: A multilevel approach.

PubMed

Rönnerstrand, Björn

2016-12-01

The aim of the study was to investigate the association between contextual generalized trust and individual-level 2009 A(H1N1) pandemic immunization acceptance. A second aim was to investigate whether knowledge about the A(H1N1) pandemic mediated the association between contextual generalized trust and A(H1N1) immunization acceptance. Data from the National 2009 H1N1 Flu Survey was used. To capture contextual generalized trust, data comes from an aggregation of surveys measuring generalized trust in the American states. To investigate the association between contextual generalized trust and immunization acceptance, while taking potential individual-level confounders into account, multilevel logistic regression was used. The investigation showed contextual generalized trust to be significantly associated with immunization acceptance. However, controlling for knowledge about the A(H1N1) pandemic did not substantially affect the association between contextual generalized trust and immunization acceptance. In conclusion, contextual state-level generalized trust was associated with A(H1N1) immunization, but knowledge about A(H1N1) was not mediating this association.

Nucleoplasmin Binds Histone H2A-H2B Dimers through Its Distal Face*

PubMed Central

Ramos, Isbaal; Martín-Benito, Jaime; Finn, Ron; Bretaña, Laura; Aloria, Kerman; Arizmendi, Jesús M.; Ausió, Juan; Muga, Arturo; Valpuesta, José M.; Prado, Adelina

2010-01-01

Nucleoplasmin (NP) is a pentameric chaperone that regulates the condensation state of chromatin extracting specific basic proteins from sperm chromatin and depositing H2A-H2B histone dimers. It has been proposed that histones could bind to either the lateral or distal face of the pentameric structure. Here, we combine different biochemical and biophysical techniques to show that natural, hyperphosphorylated NP can bind five H2A-H2B dimers and that the amount of bound ligand depends on the overall charge (phosphorylation level) of the chaperone. Three-dimensional reconstruction of NP/H2A-H2B complex carried out by electron microscopy reveals that histones interact with the chaperone distal face. Limited proteolysis and mass spectrometry indicate that the interaction results in protection of the histone fold and most of the H2A and H2B C-terminal tails. This structural information can help to understand the function of NP as a histone chaperone. PMID:20696766

Seroprevalence survey of avian influenza A(H5N1) among live poultry market workers in northern Viet Nam, 2011

PubMed Central

Dung, Tham Chi; Dinh, Pham Ngoc; Nam, Vu Sinh; Tan, Luong Minh; Hang, Nguyen Le Khanh; Thanh, Le Thi

2014-01-01

Objective Highly pathogenic avian influenza A(H5N1) is endemic in poultry in Viet Nam. The country has experienced the third highest number of human infections with influenza A(H5N1) in the world. A study in Hanoi in 2001, before the epizootic that was identified in 2003, found influenza A(H5N1) specific antibodies in 4% of poultry market workers (PMWs). We conducted a seroprevalence survey to determine the seroprevalence of antibodies to influenza A(H5N1) among PMWs in Hanoi, Thaibinh and Thanhhoa provinces. Methods We selected PMWs from five markets, interviewed them and collected blood samples. These were then tested using a horse haemagglutination inhibition assay and a microneutralization assay with all three clades of influenza A(H5N1) viruses that have circulated in Viet Nam since 2004. Results The overall seroprevalence was 6.1% (95% confidence interval: 4.6–8.3). The highest proportion (7.2%) was found in PMWs in Hanoi, and the majority of seropositive subjects (70.3%) were slaughterers or sellers of poultry. Discussion The continued circulation and evolution of influenza A(H5N1) requires comprehensive surveillance of both human and animal sites throughout the country with follow-up studies on PMWs to estimate the risk of avian–human transmission of influenza A(H5N1) in Viet Nam. PMID:25685601

Effects of Sn and Sb on the corrosion resistance of AH 32 steel in a cargo oil tank environment

NASA Astrophysics Data System (ADS)

Ahn, SooHoon; Park, Kyung Jin; Oh, KkochNim; Hwang, SungDoo; Park, ByungJoon; Kwon, HyukSang; Shon, MinYoung

2015-09-01

Effects of the alloying elements, Sn and Sb, on the corrosion resistance of modified AH 32 steel for the cargo oil tanks (COT) were examined using an electrochemical test and weight loss measurement. All experiments were carried out in acidic chloride solution (0.14 M HCl and 10 wt% NaCl, pH 0.85) at 30 °C, simulating the inner bottom plate of COT. It was clearly found that the small amount addition of Sn and Sb improved the corrosion resistance of modified AH 32 steel, which is confirmed by the higher polarization resistance of AH 32 steel modified with Sn and Sb addition compared with that of the base steel. X-ray photoelectron spectroscopy analysis of the corroded surface after immersion of 72 h presented that the AH 32 steel modified with Sn and Sb addition created the protective corrosion products including SnO2 and Sb2O5. These oxides act as high corrosion inhibitor to anodic corrosion reaction, and hence leading to the improvement in the corrosion resistance of the modified AH 32 steels.

Aeroelastic characteristics of the AH-64 bearingless tail rotor

NASA Technical Reports Server (NTRS)

Banerjee, D.

1988-01-01

The results of a wind tunnel test program to determine the performance loads and dynamic characteristics of the Composite Flexbeam Tail Rotor (CFTR) for the AH-64 Advanced Attack Helicopter are reported. The CFTR uses an elastomeric shear attachment of the flexbeam to the hub to provide soft-inplane S-mode and stiff-inplane C-mode configuration. The properties of the elastomer were selected for proper frequency placement and scale damping of the inplane S-mode. Kinematic pitch-lag coupling was introduced to provide the first cyclic inplane C-mode damping at high collective pitch. The CFTR was tested in a wind tunnel over the full slideslip envelop of the AH-64. It is found that the rotor was aeroelastically stable throughout the complete collective pitch range and up to rotor speeds of 1403 rpm. The dynamic characteristics of the rotor were found to be satisfactory at all pitch angles and rotor speeds of the tunnel tests. The design characteristics of the rotor which permit the high performance characteristics are discussed. Several schematic drawings and photographs of the rotor are provided.

PESTICIDE TRADE NAMES AND THEIR ACTIVE INGREDIENTS IN THE AHS

EPA Science Inventory

The detailed information on the use of specific pesticides is a major strength of exposure assessment conducted for the Agricultural Health Study (AHS). During the enrollment interviews, a check list was used to collect information on the frequency and duration of use for 28 p...

Rapid Diagnostic Tests for Identifying Avian Influenza A(H7N9) Virus in Clinical Samples

PubMed Central

Chen, Yu; Wang, Dayan; Zheng, Shufa; Shu, Yuelong; Chen, Wenxiang; Cui, Dawei; Li, Jinming; Yu, Hongjie; Wang, Yu; Li, Lanjuan

2015-01-01

To determine sensitivity of rapid diagnostic tests for detecting influenza A(H7N9) virus, we compared rapid tests with PCR results and tested different types of clinical samples. Usefulness of seasonal influenza rapid tests for A(H7N9) virus infections is limited because of their low sensitivity for detecting virus in upper respiratory tract specimens. PMID:25529064

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

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

Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.

2006-04-15

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

[Differences in oligomerization of nucleocapsid protein of epidemic human influenza A(H1N1), A(H1N2) and B viruses].

PubMed

Prokudina, E N; Semenova, N P; Chumakov, V M; Burtseva, E I; Slepushkin, A N

2003-01-01

A comparative analysis of involving the nucleocapsid protein (NP) into shaping-up of SDS-resistant oligomers was carried out presently in circulating epidemic strains of human influenza, viruses A and B. The study results of viral isolates obtained from clinical samples and recent standard strains revealed that the involvement of NP in the SDS-resistant oligomers, which are different in various subtypes of influenza A viruses. According to this sign, the human viruses A(9H3N2) are close to the avian ones, in which, as proved by us previously, virtually the entire NP transforms itself into the oligomers resistant to SDS. About 10-20% of NP are involved in shaping-up the virus influenza A(H1N1) of SDS-resistant oligomers. No SDS-resistant NP-oligomers were detected in influenza of type B. It is suggested that the prevalence of human viruses A(H3N2) in NP-oligomers are the peculiarities of NP structure and of the presence of the PB1 protein from avian influenza virus.

Experimental amine-epoxide sealer: a physicochemical study in comparison with AH Plus and EasySeal.

PubMed

Sonntag, D; Ritter, A; Burkhart, A; Fischer, J; Mondrzyk, A; Ritter, H

2015-08-01

To compare selected physicochemical and biological properties of an experimental sealer with those of two commercially available sealers. AH Plus and EasySeal were used as model materials for commercially available amine-epoxide sealers. They were mixed as stated by the manufacturer. The two components of experimental sealer EvoSeal A were mixed 1 : 1 vol%. The setting time was determined in two different ways: first, by setting of sealers in a temperature- and moisture-controlled environment followed by testing with a Gilmore needle and secondly, by oscillating measurements of setting behaviour using a rheometer. Differential scanning calorimetry (DSC) of the sealer was performed for comparison of thermal properties. Flow and film thickness were determined by applying pressures of 100 g and 15.3 kg, respectively, on the materials between two glass plates and measuring the diameters of the compressed sealer and the thickness with a micrometer gauge. Solubility of set materials was conducted by layering the samples with water, storing in a temperature- and humidity-controlled environment and evaporating the solvent. The solved sealer parts were then weighed. The radiopacity was measured in an X-ray experiment comparing radiopacity of a cured sealer to an aluminium step wedge. Volume shrinkage was defined by measuring the densities of samples before and after setting. The film thickness, fluidity, curing time, radiopacity and solubility of the test materials were performed as specified in DIN EN ISO 6876:2010 draft. The volume shrinkage was determined in a method adapted from standard DIN 13907:2007-01. Antibacterial activity was tested against Gram-positive Streptococcus oralis cultures in a contact test based on standard ISO 22196:2011 (E). Statistical analysis was performed using Mann-Whitney U-test where applicable. Significant differences were determined with P < 0.05. The experimental sealer, EvoSeal A, reached standard specifications. In terms of film

Investigation of a Coupled Arrhenius-Type/Rossard Equation of AH36 Material.

PubMed

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.

Structural modeling of the AhR:ARNT complex in the bHLH-PASA-PASB region elucidates the key determinants of dimerization.

PubMed

Corrada, Dario; Denison, Michael S; Bonati, Laura

2017-05-02

Elucidation of the dimerization process of the aryl hydrocarbon receptor (AhR) with the AhR nuclear translocator (ARNT) is crucial for understanding the mechanisms underlying the functional activity of AhR, including mediation of the toxicity of environmental contaminants. In this work, for the first time a structural model of the AhR:ARNT dimer encompassing the entire bHLH-PASA-PASB domain region is proposed. It is developed by using a template-based modeling approach, relying on the recently available crystallographic structures of two dimers of homologous systems in the bHLH-PAS family of proteins: the CLOCK:BMAL1 and the HIF2α:ARNT heterodimers. The structural and energetic characteristics of the modeled AhR:ARNT protein-protein interface are determined by evaluating the variations in solvent accessible surface area, the total binding free energy and the per-residue free energy contributions obtained by the MM-GBSA method and the Energy Decomposition Analysis. The analyses of the intricate network of inter-domain interactions at the dimerization interfaces provide insights into the key determinants of dimerization. These are confirmed by comparison of the computational findings with the available experimental mutagenesis and functional analysis data. The results presented here on the AhR:ARNT dimer structure and interactions provide a framework to start analyzing the mechanism of AhR transformation into its functional DNA binding form.

Cross-protection to new drifted influenza A(H3) viruses and prevalence of protective antibodies to seasonal influenza, during 2014 in Portugal.

PubMed

Guiomar, Raquel; Pereira da Silva, Susana; Conde, Patrícia; Cristóvão, Paula; Maia, Ana Carina; Pechirra, Pedro; Rodrigues, Ana Paula; Nunes, Baltazar; Milho, Luís; Coelho, Ana Paula; Fernandes, Aida; Caseiro, Paula; Rodrigues, Fernando; Correia, Lurdes; Pereira-Vaz, João; Almeida, Sofia; Branquinho, Paula; Côrte-Real, Rita; Viseu, Regina; Peres, Maria João; Sanches, Raquel; Dantas, Filipa; Freitas, Ludovina; Andrade, Graça; Maurílio, Manuel; Caldeira, Filomena; Cabral Veloso, Rita; Mota-Vieira, Luisa; Soares, Marta; Couto, Ana Rita; Bruges-Armas, Jácome; Pinto, Rita Mouro; Sobrinho Simões, Joana; Costa, Maria do Rosário; Guimarães, João Tiago; Martins, Luís; Cunha, Mário

2017-04-11

Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2-43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3-33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing cross-protection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65years old, especially for B/Yamagata lineage, 33.3% (95% CI: 25.7-41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season

Indole-3-Carbinol Promotes Goblet-Cell Differentiation Regulating Wnt and Notch Signaling Pathways AhR-Dependently.

PubMed

Park, Joo-Hung; Lee, Jeong-Min; Lee, Eun-Jin; Hwang, Won-Bhin; Kim, Da-Jeong

2018-04-30

Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated β-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.

A Comparison of AH6 AG Scores and GCE Examinations Taken after an Interval of One Year

ERIC Educational Resources Information Center

Heim, A. W.; And Others

1972-01-01

GCE O-and A-level examinations were correlated with the AH6 AG test scores obtained a year earlier. Results suggest that the predictive value of AH6 for success in individual subjects is almost as high as when the examinations and testing were taken within a few weeks of each other. (Authors/CB)

Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China.

PubMed

Qi, W; Zhou, X; Shi, W; Huang, L; Xia, W; Liu, D; Li, H; Chen, S; Lei, F; Cao, L; Wu, J; He, F; Song, W; Li, Q; Li, H; Liao, M; Liu, M

2014-06-26

Human infection with a novel influenza A(H10N8) virus was first described in China in December 2013. However, the origin and genetic diversity of this virus is still poorly understood. We performed a phylogenetic analysis and coalescent analysis of two viruses from the first case of influenza A(H10N8) (A/Jiangxi-Donghu/346-1/2013 and A/Jiangxi-Donghu/346-2/2013 and a novel A(H10N8) virus (A/chicken/Jiangxi/102/2013) isolated from a live poultry market that the patient had visited. The haemagglutinin (HA), neuraminidase (NA), PA subunit of the virus polymerase complex, nucleoprotein (NP), M and nonstructural protein (NS) genes of the three virus strains shared the same genetic origins. The origins of their HA and NA genes were similar: originally from wild birds to ducks, and then to chickens. The PA, NP, M, and NS genes were similar to those of chicken influenza A(H9N2) viruses. Coalescent analyses showed that the reassortment of these genes from A(H9N2) to A(H10N8) might have occurred at least twice. However, the PB1 and PB2 genes of the chicken A(H10N8) virus most likely originated from H7-like viruses of ducks, while those of the viruses from the case most likely stemmed from A(H9N2) viruses circulating in chickens. The oseltamivir-resistance mutation, R292K (R291K in A(H10N8) numbering) in the NA protein, occurred after four days of oseltamivir treatment. It seems that A(H10N8) viruses might have become established among poultry and their genetic diversity might be much higher than what we have observed.

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

DTIC Science & Technology

2015-01-01

influenza-like illness symptoms from 3 December 2013 through 28 February 2014. There were 85 specimens positive for influenza (18 influenza A( H1N1 ...February 2014. Th ere were 85 specimens positive for infl uenza (18 infl uenza A( H1N1 )pdm09, 65 infl uenza A(H3N2), one infl uenza A/not subtyped, and one...Health Organization reports, both infl uenza A( H1N1 )pdm09 and A(H3N2) viruses were circulating during the time of this outbreak.9 Th is is

EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) - development of e-research platform

NASA Astrophysics Data System (ADS)

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

Antibody production of wild-type and enzyme V279F variants of PAF-AH as a risk factor for Cardiovascular disease

NASA Astrophysics Data System (ADS)

Ramadhani, Anggia N.; Puspitarini, Sapti; Sari, Anissa N.; Widodo

2017-11-01

Coronary artery disease (CAD) has emerged as a leading cause of death in Indonesia nowadays. WHO data in 2012 revealed that 37% of the Indonesian population died from this disease. CAD occurs because of endothelial dysfunction in the arteries. Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase (PAF-AH), is a phospholipase A2 enzyme, encoded by the PLA2G7 gene. This protein is predicted to be involved in inflammatory phospholipid metabolism so it can be used as a biomarker of CAD in the early phase. Thus, the purpose of this research is to discover the difference in antibody production between wild-type and mutant V279F. The PAF-AH enzyme was isolated from mice lymphocyte cells in order to develop this enzyme as a biomarker of cardiovascular disease. PAF-AH migrates at 55kDa according to SDS-PAGE analysis. Flow cytometry analysis showed that mutant PAF-AH (V279F) is more antigenic than wild-type PAF-AH. The missense mutation of V279F PAF-AH means this enzyme cannot catabolize the acetyl group at the sn-2 position of PAF.

Surveillance on A/H5N1 virus in domestic poultry and wild birds in Egypt.

PubMed

El-Zoghby, Elham F; Aly, Mona M; Nasef, Soad A; Hassan, Mohamed K; Arafa, Abdel-Satar; Selim, Abdullah A; Kholousy, Shereen G; Kilany, Walid H; Safwat, Marwa; Abdelwhab, E M; Hafez, Hafez M

2013-06-22

The endemic H5N1 high pathogenicity avian influenza virus (A/H5N1) in poultry in Egypt continues to cause heavy losses in poultry and poses a significant threat to human health. Here we describe results of A/H5N1 surveillance in domestic poultry in 2009 and wild birds in 2009-2010. Tracheal and cloacal swabs were collected from domestic poultry from 22024 commercial farms, 1435 backyards and 944 live bird markets (LBMs) as well as from 1297 wild birds representing 28 different types of migratory birds. Viral RNA was extracted from a mix of tracheal and cloacal swabs media. Matrix gene of avian influenza type A virus was detected using specific real-time reverse-transcription polymerase chain reaction (RT-qPCR) and positive samples were tested by RT-qPCR for simultaneous detection of the H5 and N1 genes. In this surveillance, A/H5N1 was detected from 0.1% (n = 23/) of examined commercial poultry farms, 10.5% (n = 151) of backyard birds and 11.4% (n = 108) of LBMs but no wild bird tested positive for A/H5N1. The virus was detected from domestic poultry year-round with higher incidence in the warmer months of summer and spring particularly in backyard birds. Outbreaks were recorded mostly in Lower Egypt where 95.7% (n = 22), 68.9% (n = 104) and 52.8% (n = 57) of positive commercial farms, backyards and LBMs were detected, respectively. Higher prevalence (56%, n = 85) was reported in backyards that had mixed chickens and waterfowl together in the same vicinity and LBMs that had waterfowl (76%, n = 82). Our findings indicated broad circulation of the endemic A/H5N1 among poultry in 2009 in Egypt. In addition, the epidemiology of A/H5N1 has changed over time with outbreaks occurring in the warmer months of the year. Backyard waterfowl may play a role as a reservoir and/or source of A/H5N1 particularly in LBMs. The virus has been established in poultry in the Nile Delta where major metropolitan areas, dense human population and poultry

Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay

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

Zhang Shu; Rowlands, Craig; Safe, Stephen

2008-03-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a high affinity ligand for the aryl hydrocarbon receptor (AhR). In this study, we investigated structure-dependent differences in activation of the AhR by a series of halogenated aromatic hydrocarbons. TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 3,3',4,4',5-pentachlorobiphenyl (PCB126) induced CYP1A1-dependent activities in HEK293 human embryonic kidney, Panc1 pancreatic cancer, and Hepa1c1c7 mouse hepatoma cell lines. There was a structure-dependent difference in the efficacy of TCDF and PCB126 in HEK293 and Panc1 cells since induced CYP1A1 mRNA levels were lower than observed for the other congeners. A mammalian two-hybrid assay in cells transfected with GAL4-coactivator and AhR-VP16more » chimeras was used to investigate structure-dependent interactions of these chimeras in Panc1, HEK293, and Hepa1c1c7 cells. The reporter construct pGAL4-luc contains five tandem GAL4 response elements linked to the luciferase gene and the GAL4-coactivator chimeras express several coactivators including steroid receptor coactivator 1 (SRC-1), SRC-2 and SRC-3, the mediator coactivator TRAP220, coactivator associated arginine methyl transferase 1 (CARM-1), and peroxisome proliferator-activated receptor {gamma} coactivator 1 (PGC-1). Results of the mammalian two-hybrid studies clearly demonstrate that activation of pGAL4-luc in cells transfected with VP-AhR and GAL4-coactivator chimeras is dependent on the structure of the HAH congener, cell context, and coactivator, suggesting that the prototypical HAH congeners used in this study exhibit selective AhR modulator activity.« less

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

PubMed

Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

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 333microg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na(+),K(+)-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 10microg/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 10microg/l. The expressions of Na(+),K(+)-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, 100microg/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.

The effect of benzalkonium chloride additions to AH Plus sealer. Antimicrobial, physical and chemical properties.

PubMed

Arias-Moliz, M T; Ruiz-Linares, M; Cassar, G; Ferrer-Luque, C M; Baca, P; Ordinola-Zapata, R; Camilleri, J

2015-07-01

The aim of this study was to determine the antimicrobial and antibiofilm activities and physicochemical properties of AH Plus sealer mixed with different concentrations of benzalkonium chloride (BC). AH Plus was tested alone and mixed with 1%, 2% and 3% of BC. The antimicrobial and antibiofilm activities of the sealers against Enterococcus faecalis were evaluated by the direct contact test (DCT) and by confocal laser scanning microscopy, respectively. Setting time, flow and solubility were assessed according to ANSI/ADA specifications. Microhardness and contact angle tests were also performed. The chemical changes of the sealers were evaluated by X-ray diffraction analysis, and both Fourier transform infrared spectroscopy (FT-IR) and attenuated total reflectance Fourier transform infrared (ATR FT-IR). AH Plus+3% BC was the only sealer to promote total elimination of E. faecalis and the biovolume in this group was significantly lower than in the rest of the sealers (p>0.05). The physical properties of the sealers were according to the ANSI/ADA specifications. The microhardness decreased significantly when BC was added and a significant reduction in contact angle was obtained when incorporating 2% and 3% BC (p<0.05). No phase changes were observed with the modified sealers. The addition of 2% or higher concentrations BC to AH Plus showed antimicrobial and antibiofilm activities without affecting the properties specified in ANSI/ADA standards. However, additives to the root canal sealer altered other physical and chemical properties that are not commonly found in the literature to evaluate filling materials. The present study highlights that the antimicrobial properties of AH Plus can be significantly improved with the addition of BC. Testing beyond what is specified in standards may be indicated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of national pneumonia surveillance to describe influenza A(H7N9) virus epidemiology, China, 2004-2013.

PubMed

Xiang, Nijuan; Havers, Fiona; Chen, Tao; Song, Ying; Tu, Wenxiao; Li, Leilei; Cao, Yang; Liu, Bo; Zhou, Lei; Meng, Ling; Hong, Zhiheng; Wang, Rui; Niu, Yan; Yao, Jianyi; Liao, Kaiju; Jin, Lianmei; Zhang, Yanping; Li, Qun; Widdowson, Marc-Alain; Feng, Zijian

2013-11-01

In mainland China, most avian influenza A(H7N9) cases in the spring of 2013 were reported through the pneumonia of unknown etiology (PUE) surveillance system. To understand the role of possible underreporting and surveillance bias in assessing the epidemiology of subtype H7N9 cases and the effect of live-poultry market closures, we examined all PUE cases reported from 2004 through May 3, 2013. Historically, the PUE system was underused, reporting was inconsistent, and PUE reporting was biased toward A(H7N9)-affected provinces, with sparse data from unaffected provinces; however, we found no evidence that the older ages of persons with A(H7N9) resulted from surveillance bias. The absolute number and the proportion of PUE cases confirmed to be A(H7N9) declined after live-poultry market closures (p<0.001), indicating that market closures might have positively affected outbreak control. In China, PUE surveillance needs to be improved.

Human infections with influenza A(H3N2) variant virus in the United States, 2011-2012

USDA-ARS?s Scientific Manuscript database

BACKGROUND. During August 2011-April 2012, 13 human infections with influenza A(H3N2) variant (H3N2v) virus were identified in the United States; 8 occurred in the prior 2 years. This virus differs from previous variant influenza viruses in that it contains the matrix (M) gene from the Influenza A(H...

Isolation and characterization of a quinclorac-degrading Actinobacteria Streptomyces sp. strain AH-B and its implication on microecology in contaminated soil.

PubMed

Lang, Zhe; Qi, Dan; Dong, Jianjiang; Ren, Liwei; Zhu, Qifa; Huang, Weiwei; Liu, Yongmin; Lu, Diannan

2018-05-01

Quinclorac, a highly selective auxin herbicide, is widely used for controlling weeds in rice field. However, the residual quinclorac is toxic to many crops, vegetables, and aquatic animals, resulting in one of the major problems in crop rotation. Here, we investigated the degradation of quinclorac by strain AH-B, which was isolated from long-term quinclorac-contaminated soil using continuous circulating fluidized bed reactor and subjected to atmospheric and room temperature plasma mutation. Morphological examination, 16S rRNA gene sequencing, and phylogenetic analysis revealed that strain AH-B was Streptomyces sp. The quinclorac degradation efficiency of AH-B in liquid medium was 97.2% after 18 days when the initial quinclorac concentration was 20 mg L -1 . The degradation products were 3-chloro-7-methoxy-8-quinoline-carboxylic, 3-chloro-7-methyl-8-quinoline-carboxylic, 3-chloro-7-oxyethyl-8-quinoline-carboxylic, and 3,7-dichloro-6-methyl-8-quinoline-carboxylic. The inoculum size, initial quinclorac concentration, pH, and temperature were found to affect quinclorac degradation efficiency of AH-B. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis revealed that quinclorac degradation by AH-B produced many products. In soil with initial quinclorac content of 1 mg kg -1 dry soil, addition of AH-B resulted in 87.5% quinclorac degradation after 42 days, while that in the control (without AH-B) was 22.4%. Furthermore, microecological analysis using next-generation sequencing of 16S rRNA geneshowed that some bacterial species, such as Bacterioides and Proteobacteria, could survive in quinclorac-contaminated soil, while some bacteria, such as Firmicutes, were very sensitive to quinclorac. Besides, some fungal species, such as Basidiomycota, could also survive quinclorac-contamination. After 42 days, the diversity of bacteria and fungi in soil treated with AH-B was higher than that in the control, implying that

AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+ Lag3+ Tr1 cells.

PubMed

Ehrlich, Allison K; Pennington, Jamie M; Tilton, Susan; Wang, Xisheng; Marshall, Nikki B; Rohlman, Diana; Funatake, Castle; Punj, Sumit; O'Donnell, Edmond; Yu, Zhen; Kolluri, Siva K; Kerkvliet, Nancy I

2017-11-01

Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3 + Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4 + T cells that accompany the differentiation of AhR-Tr1 cells during the CD4 + T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response. AhR activation increased the expression of genes involved in T-cell activation, immune regulation and chemotaxis, as well as a global downregulation of genes involved in cell cycling.  Increased IL-2 production was responsible for the early AhR-Tr1 activation phenotype previously characterized as CD25 + CTLA4 + GITR + on day 2. The AhR-Tr1 phenotype was further defined by the coexpression of the immunoregulatory receptors Lag3 and Tim3 and non-overlapping expression of CCR4 and CCR9. Consistent with the increased expression of CCR9, real-time imaging showed enhanced migration of AhR-Tr1 cells to the lamina propria of the small intestine and colon. The discovery of mucosal imprinting of AhR-Tr1 cells provides an additional mechanism by which therapeutic AhR ligands can control immunopathology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised)

PubMed Central

2013-01-01

Background When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. Findings and conclusions Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request. PMID:23641940

Evaluation of Influenza Virus A/H3N2 and B Vaccines on the Basis of Cross-Reactivity of Postvaccination Human Serum Antibodies against Influenza Viruses A/H3N2 and B Isolated in MDCK Cells and Embryonated Hen Eggs

PubMed Central

Kishida, Noriko; Fujisaki, Seiichiro; Yokoyama, Masaru; Sato, Hironori; Saito, Reiko; Ikematsu, Hideyuki; Xu, Hong; Takashita, Emi; Tashiro, Masato; Takao, Shinichi; Yano, Takuya; Suga, Tomoko; Kawakami, Chiharu; Yamamoto, Miwako; Kajiyama, Keiko; Saito, Hiroyuki; Shimada, Shin'ichi; Watanabe, Sumi; Aoki, Satomi; Taira, Katsuya; Kon, Miyako; Lin, Jih-Hui

2012-01-01

The vaccine strains against influenza virus A/H3N2 for the 2010-2011 season and influenza virus B for the 2009-2010 and 2010-2011 seasons in Japan are a high-growth reassortant A/Victoria/210/2009 (X-187) strain and an egg-adapted B/Brisbane/60/2008 (Victoria lineage) strain, respectively. Hemagglutination inhibition (HI) tests with postinfection ferret antisera indicated that the antisera raised against the X-187 and egg-adapted B/Brisbane/60/2008 vaccine production strains poorly inhibited recent epidemic isolates of MDCK-grown A/H3N2 and B/Victoria lineage viruses, respectively. The low reactivity of the ferret antisera may be attributable to changes in the hemagglutinin (HA) protein of production strains during egg adaptation. To evaluate the efficacy of A/H3N2 and B vaccines, the cross-reactivities of postvaccination human serum antibodies against A/H3N2 and B/Victoria lineage epidemic isolates were assessed by a comparison of the geometric mean titers (GMTs) of HI and neutralization (NT) tests. Serum antibodies elicited by the X-187 vaccine had low cross-reactivity to both MDCK- and egg-grown A/H3N2 isolates by HI test and narrow cross-reactivity by NT test in all age groups. On the other hand, the GMTs to B viruses detected by HI test were below the marginal level, so the cross-reactivity was assessed by NT test. The serum neutralizing antibodies elicited by the B/Brisbane/60/2008 vaccine reacted well with egg-grown B viruses but exhibited remarkably low reactivity to MDCK-grown B viruses. The results of these human serological studies suggest that the influenza A/H3N2 vaccine for the 2010-2011 season and B vaccine for the 2009-2010 and 2010-2011 seasons may possess insufficient efficacy and low efficacy, respectively. PMID:22492743

Investigation of a Coupled Arrhenius-Type/Rossard Equation of AH36 Material

PubMed Central

Qin, Qin; Tian, Ming-Liang; Zhang, Peng

2017-01-01

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. PMID:28772767

Phytomonitoring and phytoremediation of agrochemicals and related compounds based on recombinant cytochrome P450s and aryl hydrocarbon receptors (AhRs).

PubMed

Shimazu, Sayuri; Inui, Hideyuki; Ohkawa, Hideo

2011-04-13

Molecular mechanisms of metabolism and modes of actions of agrochemicals and related compounds are important for understanding selective toxicity, biodegradability, and monitoring of biological effects on nontarget organisms. It is well-known that in mammals, cytochrome P450 (P450 or CYP) monooxygenases metabolize lipophilic foreign compounds. These P450 species are inducible, and both CYP1A1 and CYP1A2 are induced by aryl hydrocarbon receptor (AhR) combined with a ligand. Gene engineering of P450 and NADPH cytochrome P450 oxidoreductase (P450 reductase) was established for bioconversion. Also, gene modification of AhRs was developed for recombinant AhR-mediated β-glucronidase (GUS) reporter assay of AhR ligands. Recombinant P450 genes were transformed into plants for phytoremediation, and recombinant AhR-mediated GUS reporter gene expression systems were each transformed into plants for phytomonitoring. Transgenic rice plants carrying CYP2B6 metabolized the herbicide metolachlor and remarkably reduced the residues in the plants and soils under paddy field conditions. Transgenic Arabidopsis plants carrying recombinant guinea pig (g) AhR-mediated GUS reporter genes detected PCB126 at the level of 10 ng/g soils in the presence of biosurfactants MEL-B. Both phytomonitoring and phytoremediation plants were each evaluated from the standpoint of practical uses.

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability

PubMed Central

Zago, Michela; Sheridan, Jared A.; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H.; Hamid, Qutayba

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. PMID:28749959

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

PubMed

Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm.

PubMed Central

Nebert, D W; Petersen, D D; Fornace, A J

1990-01-01

A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria. PMID:2272308

Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage.

PubMed

Cui, Hongmei; Gu, Xinsheng; Chen, Jingshu; Xie, Ying; Ke, Sui; Wu, Jing; Golovko, Andrei; Morpurgo, Benjamin; Yan, Chunhong; Phillips, Timothy D; Xie, Wen; Luo, Jianyuan; Zhou, Zhijun; Tian, Yanan

2017-06-05

Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i.e. Hepa1c1c7, AhR +/+; Bpr lacks AhR obligatory partner ARNT; Tao, lacks AhR, to analyze pivotal role of AhR/ARNT complex in mediating the BaP-induced DNA damages using comet assay (single-cell gel electrophoresis). We found that PXR activation could significantly inhibit BaP-induced DNA damage in the HepG2 cells as well as mouse hepatocytes. Using PXR-null and wild type mouse hepatocytes we showed that PXR activation by pregnenolone 16α-carbonitrile (PCN) significantly inhibited BaP-induced DNA damage and this protective effect was abolished in PXR-null hepatocytes. Mechanistically, PXR activation inhibited expression of AhR-target genes for CYP1A1, CYP1B1 and CYP1A2 that are required for BaP biotransformation in cultured liver cells, or in the livers of C57BL/6J mice. Using an AhR-responsive reporter assay as well as chromatin immunoprecipitation assay we found that PXR activation transcriptionally represses AhR-regulated gene expression. Furthermore, we found that PXR directly bound AhR at its DNA-binding domain, and this association may play a role in preventing of the AhR from binding to its target genes as shown in the ChIP assay. Taken together, our study has revealed a novel mechanism by which PXR protects liver cells from BaP-induced DNA damage through inhibiting the BaP biotransformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Critically ill patients with 2009 influenza A(H1N1) infection in Canada.

PubMed

Kumar, Anand; Zarychanski, Ryan; Pinto, Ruxandra; Cook, Deborah J; Marshall, John; Lacroix, Jacques; Stelfox, Tom; Bagshaw, Sean; Choong, Karen; Lamontagne, Francois; Turgeon, Alexis F; Lapinsky, Stephen; Ahern, Stéphane P; Smith, Orla; Siddiqui, Faisal; Jouvet, Philippe; Khwaja, Kosar; McIntyre, Lauralyn; Menon, Kusum; Hutchison, Jamie; Hornstein, David; Joffe, Ari; Lauzier, Francois; Singh, Jeffrey; Karachi, Tim; Wiebe, Kim; Olafson, Kendiss; Ramsey, Clare; Sharma, Sat; Dodek, Peter; Meade, Maureen; Hall, Richard; Fowler, Robert A

2009-11-04

Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane

Crosstalk between AhR and wnt/β-catenin signal pathways in the cardiac developmental toxicity of PM2.5 in zebrafish embryos.

PubMed

Zhang, Hang; Yao, Yugang; Chen, Yang; Yue, Cong; Chen, Jiahong; Tong, Jian; Jiang, Yan; Chen, Tao

2016-04-29

Recent studies have shown an association between congenital heart defects and air fine particle matter (PM2.5), but the molecular mechanisms remain elusive. It is well known that a number of organic compounds in PM2.5 can act as AhR agonists, and activation of AhR can antagonize Wnt/β-catenin signaling. Therefore, we hypothesized that PM2.5 could activate AhR and then repress the expression of wnt/β-catenin targeted genes essential for cardiogenesis, resulting in heart defects. To test this hypothesis, we investigated the effects of extractable organic matter (EOM) from PM2.5 on AhR and Wnt/β-catenin signal pathways in zebrafish embryos. We confirmed that EOM could cause malformations in the heart and decreased heart rate in zebrafish embryos at 72hpf, and found that the EOM-induced heart defects were rescued in embryos co-exposed with EOM plus AhR antagonist CH223191 or β-catenin agonist CHIR99021. We further found that EOM had increased the expression levels of AhR targeted genes (Cyp1a1, Cyp1b1 and Ahrra) and reduced the mRNA levels of β-catenin targeted genes (axin2, nkx2.5 and sox9b). The mRNA expression level of Rspo2, a β-catenin upstream gene, was also decreased in embryos exposed to EOM. Supplementation with CH223191 or CHIR99021 attenuated most of the EOM-induced expression changes of genes involved in both AhR and wnt/β-catenin signal pathways. However, the mRNA expression level of AhR inhibitor Ahrrb, which did not change by EOM treatment alone, was increased in embryos co-exposed to EOM plus CH223191 or CHIR99021. We conclude that the activation of AhR by EOM from PM2.5 might repress wnt/β-catenin signaling, leading to heart defects in zebrafish embryos. Furthermore, our results indicate that the cardiac developmental toxicity of PM2.5 might be prevented by targeting AhR or wnt/β-catenin signaling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

PubMed Central

Tse, Herman; To, Kelvin K. W.; Wen, Xi; Chen, Honglin; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Li, Iris W. S.; Yuen, Kwok-Yung

2011-01-01

Background Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID:21980333

Retreatability of two endodontic sealers, EndoSequence BC Sealer and AH Plus: a micro-computed tomographic comparison.

PubMed

Oltra, Enrique; Cox, Timothy C; LaCourse, Matthew R; Johnson, James D; Paranjpe, Avina

2017-02-01

Recently, bioceramic sealers like EndoSequence BC Sealer (BC Sealer) have been introduced and are being used in endodontic practice. However, this sealer has limited research related to its retreatability. Hence, the aim of this study was to evaluate the retreatability of two sealers, BC Sealer as compared with AH Plus using micro-computed tomographic (micro-CT) analysis. Fifty-six extracted human maxillary incisors were instrumented and randomly divided into 4 groups of 14 teeth: 1A, gutta-percha, AH Plus retreated with chloroform; 1B, gutta-percha, AH Plus retreated without chloroform; 2A, gutta-percha, EndoSequence BC Sealer retreated with chloroform; 2B, gutta-percha, EndoSequence BC Sealer retreated without chloroform. Micro-CT scans were taken before and after obturation and retreatment and analyzed for the volume of residual material. The specimens were longitudinally sectioned and digitized images were taken with the dental operating microscope. Data was analyzed using an ANOVA and a post-hoc Tukey test. Fisher exact tests were performed to analyze the ability to regain patency. There was significantly less residual root canal filling material in the AH Plus groups retreated with chloroform as compared to the others. The BC Sealer samples retreated with chloroform had better results than those retreated without chloroform. Furthermore, patency could be re-established in only 14% of teeth in the BC Sealer without chloroform group. The results of this study demonstrate that the BC Sealer group had significantly more residual filling material than the AH Plus group regardless of whether or not both sealers were retreated with chloroform.

Influenza A(H9N2) Virus, Myanmar, 2014-2015.

PubMed

Lin, Thant Nyi; Nonthabenjawan, Nutthawan; Chaiyawong, Supassama; Bunpapong, Napawan; Boonyapisitsopa, Supanat; Janetanakit, Taveesak; Mon, Pont Pont; Mon, Hla Hla; Oo, Kyaw Naing; Oo, Sandi Myint; Mar Win, Mar; Amonsin, Alongkorn

2017-06-01

Routine surveillance of influenza A virus was conducted in Myanmar during 2014-2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

Surveillance on A/H5N1 virus in domestic poultry and wild birds in Egypt

PubMed Central

2013-01-01

Background The endemic H5N1 high pathogenicity avian influenza virus (A/H5N1) in poultry in Egypt continues to cause heavy losses in poultry and poses a significant threat to human health. Methods Here we describe results of A/H5N1 surveillance in domestic poultry in 2009 and wild birds in 2009–2010. Tracheal and cloacal swabs were collected from domestic poultry from 22024 commercial farms, 1435 backyards and 944 live bird markets (LBMs) as well as from 1297 wild birds representing 28 different types of migratory birds. Viral RNA was extracted from a mix of tracheal and cloacal swabs media. Matrix gene of avian influenza type A virus was detected using specific real-time reverse-transcription polymerase chain reaction (RT-qPCR) and positive samples were tested by RT-qPCR for simultaneous detection of the H5 and N1 genes. Results In this surveillance, A/H5N1 was detected from 0.1% (n = 23/) of examined commercial poultry farms, 10.5% (n = 151) of backyard birds and 11.4% (n = 108) of LBMs but no wild bird tested positive for A/H5N1. The virus was detected from domestic poultry year-round with higher incidence in the warmer months of summer and spring particularly in backyard birds. Outbreaks were recorded mostly in Lower Egypt where 95.7% (n = 22), 68.9% (n = 104) and 52.8% (n = 57) of positive commercial farms, backyards and LBMs were detected, respectively. Higher prevalence (56%, n = 85) was reported in backyards that had mixed chickens and waterfowl together in the same vicinity and LBMs that had waterfowl (76%, n = 82). Conclusion Our findings indicated broad circulation of the endemic A/H5N1 among poultry in 2009 in Egypt. In addition, the epidemiology of A/H5N1 has changed over time with outbreaks occurring in the warmer months of the year. Backyard waterfowl may play a role as a reservoir and/or source of A/H5N1 particularly in LBMs. The virus has been established in poultry in the Nile Delta where major metropolitan areas

Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011.

PubMed

Westgeest, Kim B; Russell, Colin A; Lin, Xudong; Spronken, Monique I J; Bestebroer, Theo M; Bahl, Justin; van Beek, Ruud; Skepner, Eugene; Halpin, Rebecca A; de Jong, Jan C; Rimmelzwaan, Guus F; Osterhaus, Albert D M E; Smith, Derek J; Wentworth, David E; Fouchier, Ron A M; de Graaf, Miranda

2014-03-01

Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. Each winter, influenza virus infects approximately 5 to 15% of the world's population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution

Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands.

PubMed

Procházková, Jiřina; Strapáčová, Simona; Svržková, Lucie; Andrysík, Zdeněk; Hýžďalová, Martina; Hrubá, Eva; Pěnčíková, Kateřina; Líbalová, Helena; Topinka, Jan; Kléma, Jiří; Espinosa, Joaquín M; Vondráček, Jan; Machala, Miroslav

2018-08-01

Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants. Copyright © 2018 Elsevier B.V. All rights reserved.

Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.

PubMed

Herfst, Sander; Mok, Chris K P; van den Brand, Judith M A; van der Vliet, Stefan; Rosu, Miruna E; Spronken, Monique I; Yang, Zifeng; de Meulder, Dennis; Lexmond, Pascal; Bestebroer, Theo M; Peiris, J S Malik; Fouchier, Ron A M; Richard, Mathilde

2018-01-01

Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued

Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets

PubMed Central

Mok, Chris K. P.; van den Brand, Judith M. A.; van der Vliet, Stefan; Rosu, Miruna E.; Spronken, Monique I.; Yang, Zifeng; de Meulder, Dennis; Lexmond, Pascal; Bestebroer, Theo M.; Peiris, J. S. Malik; Fouchier, Ron A. M.

2018-01-01

ABSTRACT Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to

Novel reassortant influenza A(H1N2) virus derived from A(H1N1)pdm09 virus isolated from swine, Japan, 2012.

PubMed

Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato; Kozawa, Kunihisa

2013-12-01

We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time.

Pandemic A/H1N1 influenza: transmission of the first cases in Spain.

PubMed

Català, Laura; Rius, Cristina; García de Olalla, Patricia; Nelson, Jeanne L; Alvarez, Josep; Minguell, Sofía; Camps, Neus; Sala, María Rosa; Arias, Carlos; Barrabeig, Irene; Carol, Mónica; Torra, Roser; Cardeñosa, Neus; Pumarola, Tomas; Caylà, Joan A

2012-02-01

Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe. Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases. On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1-16.1) and their contacts (13.2%; CI: 4.4-22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel. The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation.

PubMed

Khan, Kamran; Eckhardt, Rose; Brownstein, John S; Naqvi, Raza; Hu, Wei; Kossowsky, David; Scales, David; Arino, Julien; MacDonald, Michael; Wang, Jun; Sears, Jennifer; Cetron, Martin S

2013-05-01

To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports.

Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation

PubMed Central

Eckhardt, Rose; Brownstein, John S; Naqvi, Raza; Hu, Wei; Kossowsky, David; Scales, David; Arino, Julien; MacDonald, Michael; Wang, Jun; Sears, Jennifer; Cetron, Martin S

2013-01-01

Abstract Objective To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. Methods Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. Findings Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. Conclusion During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports. PMID:23678200

Association Between Pandemic Influenza A(H1N1) Vaccination in Pregnancy and Early Childhood Morbidity in Offspring.

PubMed

Hviid, Anders; Svanström, Henrik; Mølgaard-Nielsen, Ditte; Lambach, Philipp

2017-03-01

Several studies investigating potential adverse effects of the pandemic A(H1N1) vaccine have supported that influenza A(H1N1) vaccination does not increase the risk for major pregnancy and birth adverse outcomes, but little is known about possible adverse effects in offspring of A(H1N1)-vaccinated mothers beyond the perinatal period and into early childhood. To evaluate whether pandemic influenza A(H1N1) vaccination in pregnancy increases the risk for early childhood morbidity in offspring. Register-based cohort study comprising all live-born singleton children in Denmark from pregnancies overlapping the A(H1N1) influenza vaccination campaign in Denmark, from November 2, 2009, to March 31, 2010. From a cohort of 61 359 pregnancies, offspring exposed and unexposed to the influenza A(H1N1) vaccine during pregnancy were matched 1:4 on propensity scores. Vaccination in pregnancy with a monovalent inactivated AS03-adjuvanted split virion influenza A(H1N1)pdm09 vaccine (Pandemrix; GlaxoSmithKline Biologicals). Rate ratios of hospitalization in early childhood until 5 years of age. Hospitalization was defined as (1) first inpatient hospital admission, (2) all inpatient hospital admissions, and (3) first hospital contact for selected diseases, which included individual infectious diseases and individual neurologic, autoimmune, and behavioral conditions. The mean (SD) age at end of follow-up was 4.6 (0.40) years for the 61 359 children included in the study. In the cohort, the mothers of 55 048 children were unvaccinated, 349 mothers were vaccinated in the first trimester, and 5962 mothers were vaccinated in the second or third trimesters. Children exposed in the first trimester were not more likely to be hospitalized in early childhood than unexposed children (hospitalization rates per 1000 person-years, 300.6 for exposed vs 257.5 for unexposed; rate ratio, 1.17; 95% CI, 0.94-1.45). Similarly, children exposed in the second or third trimester were not more likely to

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

PubMed Central

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

[Investigation on a seasonal influenza accompanying with the first locale novel A/H1N1 influenza outbreak in China].

PubMed

Yuan, Jun; Li, Mei-xia; Liu, Yu-fei; Di, Biao; Xiao, Xiao-ling; Mao, Xin-wu; Wu, Ye-jian; Xie, Hua-ping; Xie, Zhao-jun; Zhang, Hao; Liu, Jian-ping; Li, Hai-lin; Shen, Ji-chuan; Yang, Zhi-cong; Wang, Ming

2009-10-01

To timely summarize past experience and to provide more pertinent reference for control and prevention in A/H1N1 cases in influenza season. During May 25 to 31, 2009, 2 secondary community cases caused by a influenza A/H1N1 imported case. In the close contacts of 3 A/H1N1 cases, 14 had some aspirator symptoms onset, such as fever (> or = 37.5 degrees C), cough, sore throat and etc. Laboratory tests excluded the infection of A/H1N1 influenza. For throat swab test for the 14 cases, 7 were tested for seasonal influenza virus. A face-to-face or telephone interview was conducted by CDC staff to collect information of 62 close contacts. Of 14 fever cases, there was no significant by differences by age[15-age group: 19.2% (5/26), over 25-age group: 25.0% (9/36); chi(2) = 0.287, P = 0.592]; by sex group [24.0% (6/25) for male and 21.6% (8/37) for female; chi(2) = 0.048, P = 0.826], by working units [dressing and design, photograph, saleroom and others, consumer group: 42.1% (8/19), 27.3% (3/11), 12.5% (2/16) and 6.3% (1/16); chi(2) = 7.653, P = 0.054], by dormitory style [dormitory style = 33.3% (4/12), non-dormitory style = 29.4% (10/34); chi(2) = 0.699, P = 0.403]. All the cases had fever (37.5 - 37.9 degrees C), no case had diarrhea. One in 3 A/H1N1 cases had diarrhea. All the 14 cases were negative result for A/H1N1 RNA. Six from 7 cases were positive for seasonal influenza test. This was a seasonal influenza outbreak happened in the close contacts of first confirmed A/H1N1 cases in community in mainland China. It showed that we should exclude the seasonal influenza in the investigation of A/H1N1 cases in the seasonal influenza period in some time. It is necessary to take effective measure to strengthen the control and prevention of seasonal influenza.

Hexachlorobenzene induces cell proliferation, and aryl hydrocarbon receptor expression (AhR) in rat liver preneoplastic foci, and in the human hepatoma cell line HepG2. AhR is a mediator of ERK1/2 signaling, and cell cycle regulation in HCB-treated HepG2 cells.

PubMed

de Tomaso Portaz, Ana Clara; Caimi, Giselle Romero; Sánchez, Marcela; Chiappini, Florencia; Randi, Andrea S; Kleiman de Pisarev, Diana L; Alvarez, Laura

2015-10-02

Hexachlorobenzene (HCB) is a widespread environmental pollutant, and a liver tumor promoter in rodents. Depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, terminal differentiation, or apoptosis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in drug and xenobiotic metabolism. AhR can also modulate a variety of cellular and physiological processes that can affect cell proliferation and cell fate determination. The mechanisms by which AhR ligands, both exogenous and endogenous, affect these processes involve multiple interactions between AhR and other signaling pathways. In the present study, we examined the effect of HCB on cell proliferation and AhR expression, using an initiation-promotion hepatocarcinogenesis protocol in rat liver and in the human-derived hepatoma cell line, HepG2. Female Wistar rats were initiated with a single dose of 100 mg/kg of diethylnitrosamine (DEN) at the start of the experiment. Two weeks later, daily dosing of 100 mg/kg HCB was maintained for 10 weeks. Partial hepatectomy was performed 3 weeks after initiation. The number and area of glutathione S-transferase-P (GST-P)-positive foci, in the rat liver were used as biomarkers of liver precancerous lesions. Immunohistochemical staining showed an increase in proliferating cell nuclear antigen (PCNA)-positive cells, along with enhanced AhR protein expression in hepatocytes within GST-P-positive foci of (DEN HCB) group, when compared to DEN. In a similar manner, Western blot analysis demonstrated that HCB induced PCNA and AhR protein expression in HepG2 cells. Flow cytometry assay indicated that the cells were accumulated at S and G2/M phases of the cell cycle. HCB increased cyclin D1 protein levels and ERK1/2 phosphorylation in a dose-dependent manner. Treatment of cells with a selective MEK1 inhibitor, prevented HCB-stimulatory effect on PCNA and cyclinD1, indicating that these effects

Calorimetry of 25 Ah lithium/thionyl chloride cells

NASA Technical Reports Server (NTRS)

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.

AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle.

PubMed

Kim, Young-Chae; Seok, Sunmi; Byun, Sangwon; Kong, Bo; Zhang, Yang; Guo, Grace; Xie, Wen; Ma, Jian; Kemper, Byron; Kemper, Jongsook Kim

2018-02-07

Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels.

Retreatability of two endodontic sealers, EndoSequence BC Sealer and AH Plus: a micro-computed tomographic comparison

PubMed Central

Oltra, Enrique; Cox, Timothy C.; LaCourse, Matthew R.; Johnson, James D.

2017-01-01

Objectives Recently, bioceramic sealers like EndoSequence BC Sealer (BC Sealer) have been introduced and are being used in endodontic practice. However, this sealer has limited research related to its retreatability. Hence, the aim of this study was to evaluate the retreatability of two sealers, BC Sealer as compared with AH Plus using micro-computed tomographic (micro-CT) analysis. Materials and Methods Fifty-six extracted human maxillary incisors were instrumented and randomly divided into 4 groups of 14 teeth: 1A, gutta-percha, AH Plus retreated with chloroform; 1B, gutta-percha, AH Plus retreated without chloroform; 2A, gutta-percha, EndoSequence BC Sealer retreated with chloroform; 2B, gutta-percha, EndoSequence BC Sealer retreated without chloroform. Micro-CT scans were taken before and after obturation and retreatment and analyzed for the volume of residual material. The specimens were longitudinally sectioned and digitized images were taken with the dental operating microscope. Data was analyzed using an ANOVA and a post-hoc Tukey test. Fisher exact tests were performed to analyze the ability to regain patency. Results There was significantly less residual root canal filling material in the AH Plus groups retreated with chloroform as compared to the others. The BC Sealer samples retreated with chloroform had better results than those retreated without chloroform. Furthermore, patency could be re-established in only 14% of teeth in the BC Sealer without chloroform group. Conclusion The results of this study demonstrate that the BC Sealer group had significantly more residual filling material than the AH Plus group regardless of whether or not both sealers were retreated with chloroform. PMID:28194360

Novel Reassortant Influenza A(H1N2) Virus Derived from A(H1N1)pdm09 Virus Isolated from Swine, Japan, 2012

PubMed Central

Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato

2013-01-01

We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time. PMID:24274745

Detection of influenza A(H1N1)v virus by real-time RT-PCR.

PubMed

Panning, M; Eickmann, M; Landt, O; Monazahian, M; Olschläger, S; Baumgarte, S; Reischl, U; Wenzel, J J; Niller, H H; Günther, S; Hollmann, B; Huzly, D; Drexler, J F; Helmer, A; Becker, S; Matz, B; Eis-Hübinger, Am; Drosten, C

2009-09-10

Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT-PCR for influenza A(H1N1)v virus was set up ad hoc and validated following industry-standard criteria. The lower limit of detection of the assay was 384 copies of viral RNA per ml of viral transport medium (95% confidence interval: 273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference samples including seasonal human influenza A virus H1N1 and H3N2, highly pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2 and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene recommended in 2007 by the World Health Organization was modified to work under the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both assays were equally sensitive. Clinical applicability of both assays was demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens, which included samples from the first cases of pandemic H1N1 influenza imported to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory-confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology proved its principle and might assist public health laboratories in the upcoming influenza pandemic.

Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation.

PubMed

Delabre, R M; Salez, N; Lapidus, N; Lemaitre, M; Leruez-Ville, M; de Lamballerie, X; Carrat, F

2017-01-01

We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain-specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation.

Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer

DTIC Science & Technology

2005-02-01

Balk,S.P. Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 59:2511-2515, 1999. 5. Ris...expression, 24-hydroxylase activity, and inhibition of growth hydrocarbon receptor modulators ( SARMs ) for treatment of breast by lca,25-dihydroxyvitamin D3...Safe, A. McDougal, M.S. Gupta, K. Ramamoorthy, Selective Ah [20] D.M. Peehl, R.J. Skowronski, G.K. Leung, S.T. Wong, T.A. Stamey, receptor modulators

Structural and Molecular Characterization of the Hemagglutinin from the Fifth Epidemic Wave A(H7N9) Influenza Viruses.

PubMed

Yang, Hua; Carney, Paul J; Chang, Jessie C; Guo, Zhu; Stevens, James

2018-05-30

The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that when compared to the 2013 virus HAs, the fifth wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9)HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth wave H7 HAs analyzed in this study. IMPORTANCE The A(H7N9) viruses circulating in China are of great public health concern. Herein, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014.

PubMed

Kim, Hye-Ryoung; Kwon, Yong-Kuk; Jang, Il; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Joo, Yi-Seok; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun; Bae, You-Chan

2015-05-01

In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.

The atmospheric structure and fundamental parameters of the red supergiants AH Scorpii, UY Scuti, and KW Sagittarii

NASA Astrophysics Data System (ADS)

Arroyo-Torres, B.; Wittkowski, M.; Marcaide, J. M.; Hauschildt, P. H.

2013-06-01

Aims: We present the atmospheric structure and the fundamental properties of the red supergiants (RSGs) AH Sco, UY Sct, and KW Sgr based on VLTI/AMBER observations. Methods: We carried out spectro-interferometric observations of AH Sco, UY Sct, and KW Sgr in the near-infrared K band (1.92-2.47 μm) with the VLTI/AMBER instrument with spatial and spectral resolutions of 3 milliarcsec and 1500, respectively, and compared the data to a new grid of hydrostatic PHOENIX model atmospheres. Results: In our visibility data, we observe molecular layers of water and CO in extended atmospheres. For a uniform disk modeling, we observe size increases at the water band centered at 1.9 μm of 10% to 25% and at the CO bandheads at 2.3-2.5 μm of 20%-35% with respect to the near-continuum bandpass at around 2.20 μm. Our near-infrared spectra of AH Sco, UY Sct, and KW Sgr are well reproduced by the PHOENIX model atmospheres. The continuum visibility values are consistent with a limb-darkened disk as predicted by the PHOENIX models. However, the model visibilities do not predict the large observed extensions of the molecular layers. Comparing the continuum visibility values to PHOENIX models, we estimate the Rosseland-mean photospheric angular diameters of AH Sco, UY Sct, and KW Sgr to be 5.81 ± 0.15 mas, 5.48 ± 0.10 mas, and 3.91 ± 0.25 mas, respectively. Together with the distance and the spectro-photometry, we calculate radii of 1411 ± 124 R⊙ for AH Sco, 1708 ± 192 R⊙ for UY Sct, and 1009 ± 142 R⊙ for KW Sgr and effective temperatures of 3682 ± 190 K for AH Sco, 3365 ± 134 K for UY Sct, and 3720 ± 183 K for KW Sgr. Conclusions: AH Sco, UY Sct, and KW Sgr exhibit extended atmospheric layers of H2O and CO. The PHOENIX atmosphere models predict the spectra and the continuum visibility values, but cannot reproduce the large extensions of the molecular layers. This indicates that the opacities of the molecular bands are included, but that the model atmospheres are too

Assessment of Molecular, Antigenic, and Pathological Features of Canine Influenza A(H3N2) Viruses That Emerged in the United States

PubMed Central

Pulit-Penaloza, Joanna A.; Simpson, Natosha; Yang, Hua; Creager, Hannah M.; Jones, Joyce; Carney, Paul; Belser, Jessica A.; Yang, Genyan; Chang, Jessie; Zeng, Hui; Thor, Sharmi; Jang, Yunho; Killian, Mary Lea; Jenkins-Moore, Melinda; Janas-Martindale, Alicia; Dubovi, Edward; Wentworth, David E.; Stevens, James; Tumpey, Terrence M.; Davis, C. Todd; Maines, Taronna R.

2017-01-01

Background A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states. Methods In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed. Results A(H3N2) CIVs maintained molecular and antigenic features related to low pathogenicity avian influenza A(H3N2) viruses and were distinct from A(H3N8) CIVs. The structural and glycan array binding profile confirmed these findings and revealed avian-like receptor-binding specificity. While replication kinetics in human airway epithelial cells was on par with that of seasonal influenza viruses, mild-to-moderate disease was observed in infected mice and ferrets, and the virus was inefficiently transmitted among cohoused ferrets. Conclusions Further adaptation is needed for A(H3N2) CIVs to present a likely threat to humans. However, the potential for coinfection of dogs and possible reassortment of human and other animal influenza A viruses presents an ongoing risk to public health. PMID:28934454

Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1) pandemic, 2010-2012.

PubMed

Talla Nzussouo, Ndahwouh; Duque, Jazmin; Adedeji, Adebayo Abel; Coulibaly, Daouda; Sow, Samba; Tarnagda, Zekiba; Maman, Issaka; Lagare, Adamou; Makaya, Sonia; Elkory, Mohamed Brahim; Kadjo Adje, Herve; Shilo, Paul Alhassan; Tamboura, Boubou; Cisse, Assana; Badziklou, Kossi; Maïnassara, Halima Boubacar; Bara, Ahmed Ould; Keita, Adama Mamby; Williams, Thelma; Moen, Ann; Widdowson, Marc-Alain; McMorrow, Meredith

2017-12-04

Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent. We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012. Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d'Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof. There were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses. Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B. All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses. Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0-4 years, as were a majority of those enrolled in surveillance. The seasonality of influenza and the predominant influenza type or subtype varied by country and year. Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010-2012. Although ILI surveillance systems produced a robust number of samples

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

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

Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw; Li, Lih-Ann; Lin, Pinpin

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

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

PubMed

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

2014-08-01

SPMD-based virtual organisms (VOs) were employed for time-integrating, long-term sampling combined biological and chemical analyses for exposure assessment of hydrophobic organic pollutants (HOPs) in a drinking water reservoir, China. The SPMDs were deployed at four and five sites in the Danjiangkou (DJK) reservoir over two periods of 26 and 31 d to sequester the hydrophobic contaminants in water. The chosen bioassay response for the extracts of the SPMDs, the induction of 7-ethoxyresorufin-o-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The known aryl hydrocarbon receptor (AhR) agonists PAHs and PCBs were analyzed by HRGC/HRMS instrument. The cause-effect relationship between the observed AhR activities and chemical concentrations of detected AhR agonists was examined. The results show that the extracts from the SPMD samples could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) was not correlated with the bioassay-derived TCDD equivalent (TEQbio). The known AhR agonists could only account for 2-10% of the observed AhR responses among which the contribution of PCBs could almost be neglected. Unidentified AhR-active compounds represented a greater proportion of the TCDD equivalent (TCDD-EQ) in SPMD samples from DJK. Based on the first assessment, the VO followed by the combination of chemical and biological analyses emerges as a resource efficient water monitoring device in ecotoxicological assessment for toxicologically relevant compounds which are readily available for uptake by resident aquatic biota in drinking water resources. Copyright © 2014 Elsevier Ltd. All rights reserved.

PAF levels and PAF-AH activities in placentas from normal and preeclamptic pregnancies.

PubMed

Gu, Y; Burlison, S A; Wang, Y

2006-01-01

The aim of this study was to determine: (1) platelet-activating factor (PAF) levels and PAF-acetylhydrolase (PAF-AH) activities in normal and preeclamptic placentas; (2) lipid peroxide production by placental tissues stimulated with PAF. Placentas were obtained immediately after delivery from normal and preeclamptic pregnancies. Tissue pieces were snap frozen in liquid nitrogen and stored at -70 degrees C. One gram of tissue from each placenta was used for PAF extraction and for total RNA isolation. PAF was measured by PAF [3H] scintillation proximity assay (SPA) system. Trophoblast PAF-AH activity was determined by enzyme-linked immunosorbent assay (ELISA). mRNA expression for PAF receptor was assessed by RNase protection assay (RPA). Normal placental explants were incubated with PAF at concentrations of 1 and 10 microg/ml for 48 h. Lipid peroxide productions of 8-isoprostane and malondialdehyde (MDA) were measured by ELISA and thiobarbituric acid reaction, respectively. Data were presented as mean+/-SE and analyzed by nonparametric Mann-Whitney U test and ANOVA. A p level less than 0.05 was considered statistically significant. (1) The mean tissue level for PAF was elevated, but not statistically different, in preeclamptic (n=7) than in normal (n=8) placentas, 6.45+/-1.05 versus 4.47+/-0.60 ng/g, p=0.42. (2) PAF-AH activity was higher in trophoblasts from preeclamptic (n=7) placentas than that in trophoblasts from normal (n=8) placentas, 0.69+/-0.16 versus 0.38+/-0.03 micromol/min/microg protein, p<0.05. (3) The relative mRNA expression for PAF receptor was not different between normal (0.70+/-0.08) and preeclamptic (0.76+/-0.13) placental tissues, p=0.60. (4) Productions of 8-isoprostane and MDA were not increased in tissues with PAF in culture, 8-isoprostane: 0.37+/-0.09 ng/mg (control) versus 0.32+/-0.09 ng/mg (1 microg/ml) and 0.37+/-0.07 ng/mg (10 microg/ml), p>0.5; MDA: 0.62+/-0.05 nmol/mg (control) versus 0.68+/-0.04 nmol/mg (1 microg/ml) and 0

TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling

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

Gao, Zhan; The Fifth Affiliated Hospital, Zhengzhou University, 450052; Bu, Yongjun

2016-05-01

One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin and cytokeratin14) and enhanced the mesenchymal markers (vimentin and fibronectin), but had no effect on cellmore » migration and apoptosis. TCDD exposure led to a dose-dependent increase in Slug protein expression. Coimmunoprecipitation revealed that TCDD promoted AhR to form a protein complex with Slug. ChIP assay confirmed that TCDD exposure recruited AhR to the xenobiotic responsive element of Slug promoter. Knockdown of AhR by siRNA remarkably weakened TCDD-induced binding of AhR to the XRE promoter of slug, thereby suppressed TCDD-induced vimentin. Further experiment showed that TCDD stimulated EGFR phosphorylation did not influence the TGFβ3/Smad signaling; whereas TCDD increased phosphorylation of ERK1/2 and p38 with no effect on activation of JNK. By using varieties of inhibitors, we confirmed that TCDD promoted proliferation and EMT of hFPECs via activation of EGFR/ERK pathway. These data make a novel contribution to the molecular mechanism of cleft palate by TCDD. - Highlights: • TCDD exposure promoted cell proliferation and EMT of hFPECs; • AhR signaling was activated and required for TCDD-induced EMT; • TCDD-mediated EMT of hFPECs involved the activation of EGFR/ERK signaling; • TCDD exposure had no effect on TGFβ3/Smad pathway.« less

Influenza A(H6N1) Virus in Dogs, Taiwan

PubMed Central

Lin, Hui-Ting; Wang, Ching-Ho; Chueh, Ling-Ling; Su, Bi-Ling

2015-01-01

We determined the prevalence of influenza A virus in dogs in Taiwan and isolated A/canine/Taiwan/E01/2014. Molecular analysis indicated that this isolate was closely related to influenza A(H6N1) viruses circulating in Taiwan and harbored the E627K substitution in the polymerase basic 2 protein, which indicated its ability to replicate in mammalian species. PMID:26583707

Pediatric neurological complications associated with the A(H1N1)pdm09 influenza infection.

PubMed

Frobert, E; Sarret, C; Billaud, G; Gillet, Y; Escuret, V; Floret, D; Casalegno, J S; Bouscambert, M; Morfin, F; Javouhey, E; Lina, B

2011-12-01

Influenza-related neurological complications (INC) have been reported during seasonal flu in children. To investigate the types, outcomes and incidence of INC occurring during the 2009 A(H1N1) pandemic, a retrospective analyze was conducted in the single French pediatric hospital of Lyon from October 2009 to February 2010. All children presenting with fever, influenza-like illness, respiratory distress or neurological symptoms were tested for influenza A(H1N1)pdm09 infection from respiratory specimens using real time RT-PCR. INC occurred in 14 A(H1N1)pdm09 positive children (7.7% of A(H1N1)pdm09 positive children admitted to hospital) with a median age of 5.1 years. Admission to the intensive care unit (ICU) was required for nine children (64.3%). Half of the children with INC had comorbidity and three had coinfection, both characteristics mainly found in children requiring the ICU. All children received oral oseltamivir treatment. Febrile seizures were observed in eight children, half of them having a chronic comorbidity (2 epilepsy, 1 nonketotic hyperglycinemia, 1 anoxic encephalopathy). Other INC, less commonly reported, included 2 cases of encephalitis, 1 encephalopathy, 1 basilar artery thrombosis, 1 myasthenic crisis and 1 coma. Eleven of the 14 children (78.6%) recovered, one had a minor disability, one child developed a locked-in syndrome and one died from complications of an acute necrotizing encephalopathy. INC can be observed even in children with no underlying disorder. It may lead to dramatic issue in a significant number of cases. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular Surveillance of Antiviral Drug Resistance of Influenza A/H3N2 Virus in Singapore, 2009-2013

PubMed Central

Lee, Hong Kai; Tang, Julian Wei-Tze; Loh, Tze Ping; Hurt, Aeron C.; Oon, Lynette Lin-Ean; Koay, Evelyn Siew-Chuan

2015-01-01

Adamantanes and neuraminidase inhibitors (NAIs) are two classes of antiviral drugs available for the chemoprophylaxis and treatment of influenza infections. To determine the frequency of drug resistance in influenza A/H3N2 viruses in Singapore, large-scale sequencing of neuraminidase (NA) and matrix protein (MP) genes was performed directly without initial culture amplification. 241 laboratory-confirmed influenza A/H3N2 clinical samples, collected between May 2009 and November 2013 were included. In total, 229 NA (95%) and 241 MP (100%) complete sequences were obtained. Drug resistance mutations in the NA and MP genes were interpreted according to published studies. For the NAIs, a visual inspection of the aligned NA sequences revealed no known drug resistant genotypes (DRGs). For the adamantanes, the well-recognised S31N DRG was identified in all 241 MP genes. In addition, there was an increasing number of viruses carrying the combination of D93G+Y155F+D251V (since May 2013) or D93G (since March 2011) mutations in the NA gene. However, in-vitro NAI testing indicated that neither D93G+Y155F+D251V nor D93G alone conferred any changes in NAI susceptibility. Lastly, an I222T mutation in the NA gene that has previously been reported to cause oseltamivir-resistance in influenza A/H1N1/2009, B, and A/H5N1, was detected from a treatment-naïve patient. Further in-vitro NAI testing is required to confirm the effect of this mutation in A/H3N2 virus. PMID:25635767

An in silico approach to investigate the source of the controversial interpretations about the phenotypic results of the human AhR-gene G1661A polymorphism.

PubMed

Aftabi, Younes; Colagar, Abasalt Hosseinzadeh; Mehrnejad, Faramarz

2016-03-21

Aryl hydrocarbon receptor (AhR) acts as an enhancer binding ligand-activated intracellular receptor. Chromatin remodeling components and general transcription factors such as TATA-binding protein (TBP) are evoked on AhR-target genes by interaction with its flexible transactivation domain (TAD). AhR-G1661A single nucleotide polymorphism (SNP: rs2066853) causes an arginine to lysine substitution in the acidic sub-domain of TAD at position 554 (R554K). Although, numerous studies associate the SNP with some abnormalities such as cancer, other reliable investigations refuse the associations. Consequently, the interpretation of the phenotypic results of G1661A-transition has been controversial. In this study, an in silico analysis were performed to investigate the possible effects of the transition on AhR-mRNA, protein structure, interaction properties and modifications. The analysis revealed that the R554K substitution affects secondary structure and solvent accessibility of adjacent residues. Also, it causes to decreasing of the AhR stability; altering the hydropathy features of the local sequence and changing the pattern of the residues at the binding site of the TAD-acidic sub-domain. Generating of new sites for ubiquitination and acetylation for AhR-K554 variant respectively at positions 544 and 560 was predicted. Our findings intensify the idea that the AhR-G1661A transition may affects AhR-TAD interactions, especially with the TBP, which influence AhR-target genes expression. However, the previously reported flexibility of the modular TAD could act as an intervening factor, moderate the SNP effects and causes distinct outcomes in different individuals and tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Avian influenza A/H7N9 risk perception, information trust and adoption of protective behaviours among poultry farmers in Jiangsu Province, China.

PubMed

Cui, Bin; Liao, Qiuyan; Lam, Wendy Wing Tak; Liu, Zong Ping; Fielding, Richard

2017-05-18

Poultry farmers are at high-risk from avian influenza A/H7N9 infection due to sustained occupational exposures to live poultry. This study examined factors associated with poultry farmers' adoption of personal protective behaviours (PPBs) based on Protection Motivation Theory (PMT). Totally, 297 poultry farmers in three cities of Jiangsu Province, China were interviewed during November 2013-January 2014. Data on PMT constructs, perceived trustworthiness of A/H7N9 information from mass media (formal sources), friends and family (informal sources), intention to adopt and actual adoption of PPBs and respondents' demographics were collected. Structural equation modeling (SEM) identified associations between demographic factors and PMT constructs associated with A/H7N9-oriented PPB intention. Moderated mediation analysis examined how demographics moderated the effects of information trust on PPB intention via risk perceptions of A/H7N9. Respondents generally perceived low vulnerability to A/H7N9 infection. The SEM found that male respondents perceived lower severity of (β = -0.23), and lower vulnerability to (β = -0.15) A/H7N9 infection; age was positively associated with both perceived personal vulnerability to (β = 0.21) and perceived self-efficacy (β = 0.24) in controlling A/H7N9; education was positively associated with perceived response efficacy (β = 0.40). Furthermore, perceived vulnerability (β = 0.16), perceived self-efficacy (β = 0.21) and response efficacy (β = 0.67) were positively associated with intention to adopt PPBs against A/H7N9. More trust in informal information (TII) was only significantly associated with greater PPB intention through its positive association with perceived response efficacy. Age significantly moderated the associations of TII with perceived Self-efficacy and perceived response efficacy, with younger farmers who had greater TII perceiving lower self-efficacy but higher response efficacy. Poultry farmers

Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

EPA Science Inventory

Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eight...

Genetic features of highly pathogenic avian influenza viruses A(H5N8), isolated from the European part of the Russian Federation.

PubMed

Voronina, O L; Ryzhova, N N; Aksenova, E I; Kunda, M S; Sharapova, N E; Fedyakina, I T; Chvala, I A; Borisevich, S V; Logunov, D Yu; Gintsburg, A L

2018-05-28

Highly pathogenic avian influenza viruses (HPAIV) A(H5N8) of group B (Gochang1-like) have emerged in the Tyva Republic of eastern Russia in May 2016. Since November 2016, HPAIV A(H5N8) has spread throughout the European part of Russia. Thirty-one outbreaks were reported in domestic, wild and zoo birds in 2017. The present study aimed to perform a comparative analysis of new HPAIV A(H5N8) strains. Phylogenetic analysis revealed four genetically distinct subgroups in HPAIV A(H5N8) from the 2016-2017 season. Russian strains consisted of three subgroups with differences between isolates from Tyva, Siberia (Chany Lake), and the European part of Russia. Strains from the European part of Russia showed the beginnings of divergent evolution. Slight differences of the Voronezh strains were suggested by sensitivity to antiviral compounds. Testing for host-specific mutations in sequenced strains revealed the absence of mutations associated with possible increased tropism/virulence in mammalian species, including humans. Only one residue of polymerase basic-1, 13P, is discussed, because the L13P mutation increased complementary RNA synthesis in mammalian cells. We concluded that the evolution of HPAIV A(H5N8) is continuous. Surveillance in Russia revealed new cases of HPAIV A(H5N8) and led to the elaboration of prevention strategies, which should be implemented. Copyright © 2018 Elsevier B.V. All rights reserved.

Highly pathogenic avian influenza A(H5N8) outbreaks: protection and management of exposed people in Europe, 2014/15 and 2016.

PubMed

Adlhoch, Cornelia; Brown, Ian H; Angelova, Svetla G; Bálint, Ádám; Bouwstra, Ruth; Buda, Silke; Castrucci, Maria R; Dabrera, Gavin; Dán, Ádám; Grund, Christian; Harder, Timm; van der Hoek, Wim; Krisztalovics, Katalin; Parry-Ford, Frances; Popescu, Rodica; Wallensten, Anders; Zdravkova, Anna; Zohari, Siamak; Tsolova, Svetla; Penttinen, Pasi

2016-12-08

Introduction of highly pathogenic avian influenza (HPAI) virus A(H5N8) into Europe prompted animal and human health experts to implement protective measures to prevent transmission to humans. We describe the situation in 2016 and list public health measures and recommendations in place. We summarise critical interfaces identified during the A(H5N1) and A(H5N8) outbreaks in 2014/15. Rapid exchange of information between the animal and human health sectors is critical for a timely, effective and efficient response. This article is copyright of ECDC, 2016.

Highly pathogenic avian influenza A(H5N8) outbreaks: protection and management of exposed people in Europe, 2014/15 and 2016

PubMed Central

Adlhoch, Cornelia; Brown, Ian H.; Angelova, Svetla G.; Bálint, Ádám; Bouwstra, Ruth; Buda, Silke; Castrucci, Maria R.; Dabrera, Gavin; Dán, Ádám; Grund, Christian; Harder, Timm; van der Hoek, Wim; Krisztalovics, Katalin; Parry-Ford, Frances; Popescu, Rodica; Wallensten, Anders; Zdravkova, Anna; Zohari, Siamak; Tsolova, Svetla; Penttinen, Pasi

2016-01-01

Introduction of highly pathogenic avian influenza (HPAI) virus A(H5N8) into Europe prompted animal and human health experts to implement protective measures to prevent transmission to humans. We describe the situation in 2016 and list public health measures and recommendations in place. We summarise critical interfaces identified during the A(H5N1) and A(H5N8) outbreaks in 2014/15. Rapid exchange of information between the animal and human health sectors is critical for a timely, effective and efficient response. PMID:27983512

Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season.

PubMed

Rondy, Marc; Gherasim, Alin; Casado, Itziar; Launay, Odile; Rizzo, Caterina; Pitigoi, Daniela; Mickiene, Aukse; Marbus, Sierk D; Machado, Ausenda; Syrjänen, Ritva K; Pem-Novose, Iva; Horváth, Judith Krisztina; Larrauri, Amparo; Castilla, Jesús; Vanhems, Philippe; Alfonsi, Valeria; Ivanciuc, Alina E; Kuliese, Monika; van Gageldonk-Lafeber, Rianne; Gomez, Veronica; Ikonen, Niina; Lovric, Zvjezdana; Ferenczi, Annamária; Moren, Alain

2017-10-01

In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79-year-olds and 13% (95% CI: -15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate.

A 65 Ah rechargeable lithium molybdenum disulfide battery

NASA Technical Reports Server (NTRS)

Brandt, K.

1986-01-01

A rechargeable lithium molybdenum disulfide battery which has a number of superior performance characteristics which includes a high energy density, a high power density, and a long charge retention time was developed. The first cell sizes developed included a C size cell and an AA size cell. Over the last two years, a project to demonstrate the feasibility of the scale up to this technology to a BC size cell with 65 Ah capacity was undertaken. The objective was to develop, build, and test a .6 kWh storage battery consisting of 6 BC cells in series.

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

PubMed

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.

Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort.

PubMed

Fragaszy, Ellen; Ishola, David A; Brown, Ian H; Enstone, Joanne; Nguyen-Van-Tam, Jonathan S; Simons, Robin; Tucker, Alexander W; Wieland, Barbara; Williamson, Susanna M; Hayward, Andrew C; Wood, James L N

2016-07-01

Pigs are mixing vessels for influenza viral reassortment, but the extent of influenza transmission between swine and humans is not well understood. To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine-adapted influenza viruses. UK pig industry workers were frequency-matched on age, region, sampling month, and gender with a community-based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres ≥ 40 considered seropositive and indicative of infection). Virus-specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity. Forty-two percent of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CIs), adjusted odds ratio after accounting for possible cross-reactivity with other swine A(H1) viruses (aOR) 25·3, 95% CI (1·4-536·3), P = 0·028. The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunisation of pig industry workers may reduce transmission and the potential for virus reassortment. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Development of a seaweed derived platelet activating factor acetylhydrolase (PAF-AH) inhibitory hydrolysate, synthesis of inhibitory peptides and assessment of their toxicity using the Zebrafish larvae assay.

PubMed

Fitzgerald, Ciarán; Gallagher, Eimear; O'Connor, Paula; Prieto, José; Mora-Soler, Leticia; Grealy, Maura; Hayes, Maria

2013-12-01

The vascular inflammatory role of platelet activating factor acetylhydrolase (PAF-AH) is thought to be due to the formation of lysophosphatidyl choline and oxidized non-esterified fatty acids. This enzyme is considered a promising therapeutic target for the prevention of atherosclerosis and there is a need to expand the available chemical templates of PAF-AH inhibitors. This study demonstrated how natural PAF-AH inhibitory peptides were isolated and characterized from the red macroalga Palmaria palmata. The dried powdered alga was hydrolyzed using the food grade enzyme papain, and the resultant peptide containing fraction generated using RP-HPLC. Several oligopeptides were identified as potential PAF-AH inhibitors following bio-guided fractionation, and the amino acid sequences of these oligopeptides were confirmed by Q-TOF-MS and microwave-assisted solid phase de novo synthesis. The most promising PAF-AH inhibitory peptide had the amino acid sequence NIGK and a PAF-AH IC50 value of 2.32 mM. This peptide may constitute a valid drug template for PAF-AH inhibitors. Furthermore the P. palmata hydrolysate was nontoxic when assayed using the Zebrafish toxicity model at a concentration of 1mg/ml. Copyright © 2013 Elsevier Inc. All rights reserved.

Regulatory effects of dioxin-like and non-dioxin-like PCBs and other AhR ligands on the antioxidant enzymes paraoxonase 1/2/3.

PubMed

Shen, Hua; Robertson, Larry W; Ludewig, Gabriele

2016-02-01

Paraoxonase 1 (PON1), an antioxidant enzyme, is believed to play a critical role in many diseases, including cancer. PCBs are widespread environmental contaminants known to induce oxidative stress and cancer and to produce changes in gene expression of various pro-oxidant and antioxidant enzymes. Thus, it appeared of interest to explore whether PCBs may modulate the activity and/or gene expression of PON1 as well. In this study, we compared the effects of dioxin-like and non-dioxin-like PCBs and of various aryl hydrocarbon receptor (AhR) ligands on PON1 regulation and activity in male and female Sprague-Dawley rats. Our results demonstrate that (i) the non-dioxin-like PCB154, PCB155, and PCB184 significantly reduced liver and serum PON1 activities, but only in male rats; (ii) the non-dioxin-like PCB153, the most abundant PCB in many matrices, did not affect PON1 messenger RNA (mRNA) level in the liver but significantly decreased serum PON1 activity in male rats; (iii) PCB126, an AhR ligand and dioxin-like PCB, increased both PON1 activities and gene expression; and (iv) even though three tested AhR ligands induced CYP1A in several tissues to a similar extent, they displayed differential effects on the three PONs and AhR, i.e., PCB126 was an efficacious inducer of PON1, PON2, PON3, and AhR in the liver, while 3-methylcholantrene induced liver AhR and lung PON3, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent AhR agonist, increased only PON3 in the lung, at the doses and exposure times used in these studies. These results show that PCBs may have an effect on the antioxidant protection by paraoxonases in exposed populations and that regulation of gene expression through AhR is highly diverse.

Development of a 10 Ah, Prismatic, Lithium-Ion Cell for NASA/GSFC

NASA Technical Reports Server (NTRS)

Stein, Brian; Baker, John W.; George, Douglas S.; Isaacs, Nathan D.; Shah, Pinakin M.; Rao, Gopalakrishna M.; Day, John H. (Technical Monitor)

2001-01-01

MSA's 10 Ah Li-ion cell is a rugged design suitable for the stringent requirements of aerospace applications. Eighteen cells demonstrate consistent cycling performance over a wide range of rates and temperatures. The cell passes qualification requirements for vibration survivability technology improvements at MSA continue to enhance cell performance.

Development and validation of a blade-element mathematical model for the AH-64A Apache helicopter

NASA Technical Reports Server (NTRS)

Mansur, M. Hossein

1995-01-01

A high-fidelity blade-element mathematical model for the AH-64A Apache Advanced Attack Helicopter has been developed by the Aeroflightdynamics Directorate of the U.S. Army's Aviation and Troop Command (ATCOM) at Ames Research Center. The model is based on the McDonnell Douglas Helicopter Systems' (MDHS) Fly Real Time (FLYRT) model of the AH-64A (acquired under contract) which was modified in-house and augmented with a blade-element-type main-rotor module. This report describes, in detail, the development of the rotor module, and presents some results of an extensive validation effort.

Pathogenesis of Influenza A/H5N1 virus infection in ferrets differs between intranasal and intratracheal routes of inoculation.

PubMed

Bodewes, Rogier; Kreijtz, Joost H C M; van Amerongen, Geert; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F; Kuiken, Thijs

2011-07-01

Most patients infected with highly pathogenic avian influenza A/H5N1 virus develop severe pneumonia resulting in acute respiratory distress syndrome, with extrarespiratory disease as an uncommon complication. Intranasal inoculation of ferrets with influenza A/H5N1 virus causes lesions in both the respiratory tract and extrarespiratory organs (primarily brain). However, the route of spread to extrarespiratory organs and the relative contribution of extrarespiratory disease to pathogenicity are largely unknown. In the present study, we characterized lesions in the respiratory tract and central nervous system (CNS) of ferrets (n = 8) inoculated intranasally with influenza virus A/Indonesia/5/2005 (H5N1). By 7 days after inoculation, only 3 of 8 ferrets had a mild or moderate bronchointerstitial pneumonia. In contrast, all 8 ferrets had moderate or severe CNS lesions, characterized by meningoencephalitis, choroiditis, and ependymitis, and centered on tissues adjoining the cerebrospinal fluid. These findings indicate that influenza A/H5N1 virus spread directly from nasal cavity to brain, and that CNS lesions contributed more than pulmonary lesions to the pathogenicity of influenza A/H5N1 virus infection in ferrets. In comparison, intratracheal inoculation of ferrets with the same virus reproducibly caused severe bronchointerstitial pneumonia. The method of virus inoculation requires careful consideration in the design of ferret experiments as a model for influenza A/H5N1 in humans. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Sedimentary evolution and ecosystem change in Ahémé lake, south-west Benin

NASA Astrophysics Data System (ADS)

Amoussou, Ernest; Totin Vodounon, Henri S.; Vissin, Expédit W.; Mahé, Gil; Oyédé, Marc Lucien

2018-04-01

Tropical moist ecosystems, such as Ahémé lake, south-west Benin, are increasingly marked by water degradation, linked with the activities of increasing riparian populations. The objective of this study is to analyze sedimentary dynamics and its influence on the changing ecosystem of Ahémé lake from 1961-2010. Data used to carry out the study are records of precipitation, flows, turbidity, suspended sediment, mineral elements and bathymetry. Grain size data from the sieving of sediment samples were used to interpret suspended solids distribution in the lake. Linear correlation coefficients were used to assess the degree of dependence between rainfall and runoff inputs to the lake. Lake depth measurements in some areas of the lake serve to determine the rate of infilling. The sorting index was used to highlight the distribution and origin of sediments in the lake. The results show a degradation of the lake Ahémé ecosystem characterized by infilling of its bed, a high correlation (r = 0.90) between rainfall and runoff, seasonal change in physicochemical parameters (total suspended sediment decrease by -91 %) and decrease in fish production by 135.8 t yr-1. The highest mean suspended sediment concentrations in lake inputs occur during high water periods (123 mg L-1) compared to low water periods (11.2 mg L-1).

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

PubMed Central

Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

2014-01-01

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

PubMed

Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

2014-10-01

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

PubMed

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. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

In vitro evaluation of antibacterial effect of AH Plus incorporated with quaternary ammonium epoxy silicate against Enterococcus faecalis.

PubMed

Gong, Shi-Qiang; Huang, Zhi-Bin; Shi, Wei; Ma, Bo; Tay, Franklin R; Zhou, Bin

2014-10-01

The purpose of this study was to evaluate the in vitro antibacterial effect of AH Plus (Dentsply, DeTrey, Konstanz, Germany) incorporated with quaternary ammonium epoxy silicate (QAES) against Enterococcus faecalis. QAES particles were synthesized by the cocondensation of tetraethoxysilane with 2 trialkoxysilanes (3-[trimethoxysilyl]propyldimethyloctadecyl ammonium chloride and 3-glycidyloxypropyltrimethoxysilane) through a 1-pot sol-gel route. Dried QAES particles were then characterized by attenuated total reflection Fourier transform infrared spectroscopy and scanning electron microscopy. AH Plus sealers incorporated with 0-8 wt% QAES were tested after 4 weeks of water aging to assess the in vitro antibacterial activity against E. faecalis by the direct contact test (DCT) and 3-dimensional image analysis of live/dead-stained E. faecalis biofilms using confocal laser scanning microscopy. The Fourier transform infrared spectroscopy spectrum of QAES particles revealed the coexistence of the characteristic absorbance band of the siloxane backbone (Si-O-Si) from 1,000-1,100 cm(-1), epoxide band peaking at ∼916 cm(-1), and C-N stretching vibration peaking at 1,373 cm(-1). The scanning electron microscopic image showed the spherical morphology of QAES particles with ∼120 nm in diameter and a rough surface. DCT results revealed that AH Plus alone (0 wt% QAES) after 4 weeks of water aging had no inhibitory effect on E. faecalis growth (P = .569). AH Plus incorporated with QAES (2-8 wt%) showed antibacterial activity against E. faecalis as shown in DCT and biofilm viability results (P < .001). The incorporation of QAES into epoxy resin-based AH Plus may be a promising approach for controlling endodontic infection at the time of canal filling and preventing subsequent reinfection. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Genetic and phylogenetic analysis of multi-continent human influenza A(H1N2) reassortant viruses isolated in 2001 through 2003.

PubMed

Chen, M-J; La, T; Zhao, P; Tam, J S; Rappaport, R; Cheng, S-M

2006-12-01

Genetic analyses were performed on 228 influenza A(H1) viruses derived from clinical subjects participating in an experimental vaccine trial conducted in 20 countries on four continents between 2001 and 2003. HA1 phylogenetic analysis of these viruses showed multiple clades circulated around the world with regional prevalence patterns. Sixty-five of the A(H1) viruses were identified as A(H1N2), 40 of which were isolated from South Africa. The A(H1) sequences of these viruses cluster with published H1N2 viruses phylogenetically and share with them diagnostic signature V169A and A193T changes. The results also showed for the first time that H1N2 viruses were prominent in South Africa during the 2001-2002 influenza season, accounting for over 90% of the A(H1) cases in our study, and infecting both children (29/31) and the elderly (11/13). Phylogenetic analysis of the 65 H1N2 viruses we identified, in conjunction with the 56 recent H1N2 viruses currently available in the database, provided a comprehensive view of the circulation and evolution of distinct clades of H1N2 viruses in a temporal manner between early 2001 and mid-2003, shortly after the appearance of these recent reassortant viruses in or near year 2000.

Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

PubMed Central

2013-01-01

Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can

Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models.

PubMed

Prokopyeva, E A; Sobolev, I A; Prokopyev, M V; Shestopalov, A M

2016-04-01

In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model. Copyright © 2016 Elsevier B.V. All rights reserved.

Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

PubMed Central

Guarnaccia, Teagan; Carolan, Louise A.; Maurer-Stroh, Sebastian; Lee, Raphael T. C.; Job, Emma; Reading, Patrick C.; Petrie, Stephen; McCaw, James M.; McVernon, Jodie; Hurt, Aeron C.; Kelso, Anne; Mosse, Jennifer; Barr, Ian G.; Laurie, Karen L.

2013-01-01

Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance

Role of Sequence Variations in AhR Gene Towards Modulating Smoking Induced Lung Cancer Susceptibility in North Indian Population: A Multiple Interaction Analysis.

PubMed

Budhwar, Sneha; Bahl, Charu; Sharma, Siddharth; Singh, Navneet; Behera, Digambar

2018-05-01

AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer. To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility. 297 cases and 320 controls have been genotyped using PCR-RFLP technique. In order to find out the association, unconditional logistic regression approach was used. To analyze high order in-teractions Multifactor Dimensionality Reduction and Classification and regression tree was used. Subjects carrying the variant genotype for AhR rs7811989 showed a two-fold risk (p=0.007) and a marginal risk was also seen in case of individuals carrying either single or double copy of suscep-tible allele for rs102550822 (p=0.02). Whereas the variant allele for rs2066853 showcased a strong pro-tective effect (p=0.003). SQCC individuals with mutant genotype of rs2066853 also exhibited a protec-tive effect towards lung cancer (OR=0.30, p=0.0013). The association of rs7811989 mutant genotype and rs10250822 mutant genotype was evident especially in smokers as compared to non-smokers. AhR rs2066853 showed a decreased risk in smokers with mutant genotype (p=0.002). MDR approach gave the best interaction model of AhR rs2066853 and smoking (CVC=10/10, prediction error=0.42). AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.

Fabrication and evaluation of 100 Ah cylindrical lithium ion battery for electric vehicle applications

NASA Astrophysics Data System (ADS)

Hyung, Yoo-Eup; Moon, Seong-In; Yum, Duk-Hyeng; Yun, Seong-Kyu

A total of 100 Ah class lithium ion cells with C/LiCoO 2 cell system for electric vehicles (EVs) was developed. EV-size lithium ion battery was developed by Sony, KERI/STC, SAFT, VARTA, Sanyo and Matsushita. GS battery and Hitachi have developed also stationary type large scale (70-80 Ah) lithium ion batteries. Lithium ion battery module for EVs was demonstrated by Sony/Nissan and KERI/STC in 1996. At present, the performance of developed EV-cells was up to 115 Wh/kg and 286 W/kg of specific power at 80% DOD. We assume our EV cells to have 248 and 242 km driving distance per one charge with DST-120 mode and ECE-15 mode, respectively. Finally, we performed safety/abuse tests of developed lithium ion cell.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

PubMed

Martínez-Baz, Iván; Casado, Itziar; Navascués, Ana; Díaz-González, Jorge; Aguinaga, Aitziber; Barrado, Laura; Delfrade, Josu; Ezpeleta, Carmen; Castilla, Jesús

2017-03-15

The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Genome Sequence of Aeromonas hydrophila Strain AH-3 (Serotype O34)

PubMed Central

Forn-Cuní, Gabriel; Tomás, Juan M.

2016-01-01

Aeromonas hydrophila is an emerging pathogen of poikilothermic animals, from fish to mammals, including humans. Here, we report the whole-genome sequence of the A. hydrophila AH-3 strain, isolated from a fish farm goldfish septicemia outbreak in Spain, with a characterized polar and lateral flagellum glycosylation pattern. PMID:27587828

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

PubMed Central

Kim, Jin Hyang; Reber, Adrian J.; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A.; Jacob, Joshy; Sambhara, Suryaprakash

2016-01-01

The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses. PMID:27849030

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease.

PubMed

Kim, Jin Hyang; Reber, Adrian J; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A; Jacob, Joshy; Sambhara, Suryaprakash

2016-11-16

The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.

Apical sealing ability of Resilon/Epiphany versus gutta-percha/AH Plus: immediate and 16-months leakage.

PubMed

Paqué, F; Sirtes, G

2007-09-01

To compare the long-term apical sealing ability of gutta-percha/AH Plus and Resilon/Epiphany. The root canals of 90 single-rooted human mandibular premolars with single narrow root canals were prepared with ProFile 0.4 taper instruments to apical size 40. After each instrument, the canals were irrigated with 1% sodium hypochlorite. Subsequently, the teeth were randomly divided into four groups containing 20 teeth each. Additionally, 10 prepared premolars served as positive and 10 counterparts with intact crowns as negative controls. The root canals were filled with gutta-percha/AH Plus or Resilon/Epiphany using lateral or vertical compaction. Specimens were allowed to set for 7 days at 37 degrees C and 100% humidity. Subsequently, the root fillings were removed down to the apical 4 mm. Fluid movement was then assessed using a fluid transportation model and re-evaluated after 16 months of water storage. Leakage within and between groups was compared using nonparametric tests. Negative controls revealed no fluid movement and positive controls displayed gross fluid movement at both times of observation. At the immediate measurement, there were no significant differences between the experimental groups (Kruskal-Wallis, P > 0.05). Gutta-percha/AH Plus fillings retained their seal after 16-months storage (Wilcoxon, P > 0.05), whilst the Resilon/Epiphany groups lost their sealing capacity (Wilcoxon, P < 0.001). In these groups, 29 of the 40 specimens exhibited gross leakage similar to positive controls. Initially, Resilon/Epiphany root fillings prevented fluid movement to the same degree as gutta-percha/AH Plus counterparts, but showed more fluid movement when tested at 16 months.

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

PubMed Central

Grant, Kristina; Franklin, Lucinda; Kaczmarek, Marlena; Hurt, Aeron; Kostecki, Renata; Kelly, Heath

2011-01-01

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. PMID:23908889

Does the Shanghai-Hong Kong Stock Connect significantly affect the A-H premium of the stocks?

NASA Astrophysics Data System (ADS)

Hui, Eddie C. M.; Chan, Ka Kwan Kevin

2018-02-01

Since the Shanghai-Hong Kong Stock Connect ("the Connect") was launched in late 2014, more and more Mainland investors have invested in Hong Kong listed shares, and vice versa, increasing the transaction volume of the stock market on both sides. However, only a few studies investigated how the Shanghai-Hong Kong Stock Connect affected the pricing dynamics of stocks listed in both Shanghai and Hong Kong. Applying linear regression, this study investigates how the Connect affects the H-share discounts of 12 stocks cross-listed in Shanghai and Hong Kong. A new feature of our model is that we add a dummy variable so as to be the first study to examine the effect of the China financial crisis on the A-H premium of the stocks. We find that the A-H premium of all stocks widens significantly after the Connect is launched, implying immatureness or even inefficiency of China's financial market. Furthermore, the result shows that trading activities in the mainland market affects the A-H premium more significantly than trading activities in the Hong Kong market do. This implies that China's financial market plays a dominant role in the Connect.

Primer development to obtain complete coding sequence of HA and NA genes of influenza A/H3N2 virus.

PubMed

Agustiningsih, Agustiningsih; Trimarsanto, Hidayat; Setiawaty, Vivi; Artika, I Made; Muljono, David Handojo

2016-08-30

Influenza is an acute respiratory illness and has become a serious public health problem worldwide. The need to study the HA and NA genes in influenza A virus is essential since these genes frequently undergo mutations. This study describes the development of primer sets for RT-PCR to obtain complete coding sequence of Hemagglutinin (HA) and Neuraminidase (NA) genes of influenza A/H3N2 virus from Indonesia. The primers were developed based on influenza A/H3N2 sequence worldwide from Global Initiative on Sharing All Influenza Data (GISAID) and further tested using Indonesian influenza A/H3N2 archived samples of influenza-like illness (ILI) surveillance from 2008 to 2009. An optimum RT-PCR condition was acquired for all HA and NA fragments designed to cover complete coding sequence of HA and NA genes. A total of 71 samples were successfully sequenced for complete coding sequence both of HA and NA genes out of 145 samples of influenza A/H3N2 tested. The developed primer sets were suitable for obtaining complete coding sequences of HA and NA genes of Indonesian samples from 2008 to 2009.

HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion

PubMed Central

Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q.; Abrantes, Juliana L.; Costa, Eduardo; Temerozo, Jairo R.; Siqueira, Marilda M.; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L.

2014-01-01

HIV-1-infected patients co-infected with A(H1N1)pdm09 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(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010. PMID:24978204

HIV-1 and its gp120 inhibits the influenza A(H1N1)pdm09 life cycle in an IFITM3-dependent fashion.

PubMed

Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q; Abrantes, Juliana L; Costa, Eduardo; Temerozo, Jairo R; Siqueira, Marilda M; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L

2014-01-01

HIV-1-infected patients co-infected with A(H1N1)pdm09 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(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.

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

PubMed

Choi, Min Seop; Kwon, Se Ryun; Choi, Seong Hee; Kwon, Hyuk Chu

2012-12-01

Gene expressions of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor (AhR) and vitellogenin (Vg) by endocrine disruptors, benzo[α]pyrene (B[a]P) and tributyltin (TBT) were examined in cultured eel hepatocytes which were isolated from eels treated previously with B[a]P (10 mg/kg) or estradiol-17β (20 mg/kg) in vivo, and the relationship between CYP1A, AhR and Vg genes were studied. When the cultured eel hepatocytes were treated with B[a]P (10(-6)-10(-5) M) the gene expressions of CYP1A and AhR were enhanced in a concentration-dependent manner. However, when treated with TBT (10(-9)-10(-5) M) the gene expressions of CYP1A and AhR were suppressed at high concentrations (10(-6)-10(-5) M), while having no effects at low concentrations (10(-9)-10(-7) M). Gene expression of Vg was also suppressed by TBT in a concentration-dependent manner in cultured eel hepatocytes which was previously treated in vivo with estradiol-17β.

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

PubMed Central

Choi, Min Seop; Kwon, Se Ryun; Choi, Seong Hee; Kwon, Hyuk Chu

2012-01-01

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. PMID:25949102

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

PubMed Central

Zaraket, Hassan; Baranovich, Tatiana; Kaplan, Bryan S.; Carter, Robert; Song, Min-Suk; Paulson, James C.; Rehg, Jerold E.; Bahl, Justin; Crumpton, Jeri C.; Seiler, Jon; Edmonson, Michael; Wu, Gang; Karlsson, Erik; Fabrizio, Thomas; Zhu, Huachen; Guan, Yi; Husain, Matloob; Schultz-Cherry, Stacey; Krauss, Scott; McBride, Ryan; Webster, Robert G.; Govorkova, Elena A.; Zhang, Jinghui; Russell, Charles J.; Webby, Richard J.

2015-01-01

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness. PMID:25850788

Spatiotemporal dynamics of influenza A(H1N1)pdm09 in Brazil during the pandemic and post-pandemic periods.

PubMed

Manito, Alessandra C B; Gräf, Tiago; Lunge, Vagner R; Ikuta, Nilo

2017-06-15

Influenza A(H1N1)pdm09 was responsible for the first global flu pandemic in 21st century affecting all the world. In Brazil, A(H1N1)pdm09 is still circulating as a seasonal virus, causing deaths every year. Nevertheless, the viral diffusion process that yearly seeds new influenza strains in the country was not investigated yet. The aim of the current study was to describe the phylodynamics and phylogeography of influenza A(H1N1)pdm09 in Brazil between 2009 and 2014. Neuraminidase sequences from Brazil and other regions of the World were retrieved and analyzed. Bayesian phylogeographic and phylodynamic model approaches were used to reconstruct the spatiotemporal and demographic history of influenza A(H1N1)pdm09 in Brazil (divided in subtropical and tropical regions) and related countries. Our analyses reveal that new influenza A(H1N1)pdm09 lineages are seeded in Brazil in almost each year and the main sources of viral diversity are North America, Europe and East Asia. The phylogeographic asymmetric model also revealed that Brazil, mainly the subtropical region, seeds viral lineages into other countries. Coalescent analysis of the compiled dataset reconstructed the peak of viral transmissions in the winter months of Southern hemisphere. The results presented in this study can be informative to public health, guide intervention strategies and in the understanding of flu virus migration, which helps to predict antigenic drift and consequently the developing of new vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic Diversity of Highly Pathogenic Avian Influenza A(H5N8/H5N5) Viruses in Italy, 2016-17.

PubMed

Fusaro, Alice; Monne, Isabella; Mulatti, Paolo; Zecchin, Bianca; Bonfanti, Lebana; Ormelli, Silvia; Milani, Adelaide; Cecchettin, Krizia; Lemey, Philippe; Moreno, Ana; Massi, Paola; Dorotea, Tiziano; Marangon, Stefano; Terregino, Calogero

2017-09-01

In winter 2016-17, highly pathogenic avian influenza A(H5N8) and A(H5N5) viruses of clade 2.3.4.4 were identified in wild and domestic birds in Italy. We report the occurrence of multiple introductions and describe the identification in Europe of 2 novel genotypes, generated through multiple reassortment events.

Travel-related influenza A/H1N1 infection at a rock festival in Hungary: one virus may hide another one.

PubMed

Botelho-Nevers, Elizabeth; Gautret, Philippe; Benarous, Lucas; Charrel, Rémi; Felkai, Peter; Parola, Philippe

2010-01-01

Mass gathering is well known to concentrate and amplify the transmission of infectious respiratory diseases. Here we report a possible case of coinfection with influenza A/H1N1 and varicella in a young French traveler returning from a rock festival in Hungary. We report a cluster of influenza A/H1N1 cases at this festival.

Stress analysis of 27% scale model of AH-64 main rotor hub

NASA Technical Reports Server (NTRS)

Hodges, R. V.

1985-01-01

Stress analysis of an AH-64 27% scale model rotor hub was performed. Component loads and stresses were calculated based upon blade root loads and motions. The static and fatigue analysis indicates positive margins of safety in all components checked. Using the format developed here, the hub can be stress checked for future application.

Community-Acquired Pneumonia Due to Pandemic A(H1N1)2009 Influenzavirus and Methicillin Resistant Staphylococcus aureus Co-Infection

PubMed Central

Murray, Ronan J.; Robinson, James O.; White, Jodi N.; Hughes, Frank; Coombs, Geoffrey W.; Pearson, Julie C.; Tan, Hui-Leen; Chidlow, Glenys; Williams, Simon; Christiansen, Keryn J.; Smith, David W.

2010-01-01

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(H1N1)2009 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(H1N1)2009 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(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/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(H1N1)2009/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(H1N1)2009 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 A( H1N1

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

PubMed

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

2017-02-01

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

Influence of ethanol on dentin roughness, surface free energy, and interaction between AH Plus and root dentin.

PubMed

Pantoja, Carlos Augusto de Morais Souto; Silva, Diogo Henrique da; Soares, Adriana de Jesus; Ferraz, Caio Cezar Randi; Gomes, Brenda Paula Figueiredo de Almeida; Zaia, Alexandre Augusto; Almeida, José Flávio Affonso de

2018-01-01

This study aimed to evaluate the influence of different ethanol concentrations on dentin roughness, surface free energy, and contact angle between AH Plus and the root canal dentin. One hundred human maxillary anterior teeth were split longitudinally and 200 dentin specimens were polished to make the surface flatter and smoother. An acrylic bar was positioned between two dentin specimens and impression material was added to create a block, simulating an instrumented root canal space. Specimens were removed from the mold and cleaned in an ultrasonic bath for 10 min. Thereafter, dentin specimens were divided into four groups (n = 50) according to the drying methods used: a) wet: vacuum only, b) paper points: vacuum + absorbent paper points, c) 70% alcohol: 70% alcohol (1 min) + vacuum + absorbent paper points, and d) 100% alcohol: 100% alcohol (1 min) + vacuum + absorbent paper points. A rugosimeter and a goniometer were used to verify the roughness (Ra) and to measure the surface free energy and the contact angle between the AH Plus sealer and the root canal dentin. ANOVA and Tukey tests (α = 0.05) were used for statistical analysis. The 70% and 100% ethanol groups showed significantly decreased roughness as well as increased surface free energy in the root canal dentin when compared to the wet and paper point groups. In addition, ethanol significantly reduced the contact angle between the AH Plus sealer and the root canal dentin. Ethanol solutions (70% and 100%) provide better wettability of AH Plus sealer on dentin surfaces.

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

PubMed

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.

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

PubMed

Pollett, Simon; 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

2015-08-01

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.

Nosocomial Co-Transmission of Avian Influenza A(H7N9) and A(H1N1)pdm09 Viruses between 2 Patients with Hematologic Disorders

PubMed Central

Chen, Huazhong; Liu, Shelan; Liu, Jun; Chai, Chengliang; Mao, Haiyan; Yu, Zhao; Tang, Yuming; Zhu, Geqin; Chen, Haixiao X.; Zhu, Chengchu; Shao, Hui; Tan, Shuguang; Wang, Qianli; Bi, Yuhai; Zou, Zhen; Liu, Guang; Jin, Tao; Jiang, Chengyu; Gao, George F.; Peiris, Malik

2016-01-01

A nosocomial cluster induced by co-infections with avian influenza A(H7N9) and A(H1N1)pdm09 (pH1N1) viruses occurred in 2 patients at a hospital in Zhejiang Province, China, in January 2014. The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. He had co-infection with H7N9 and pH1N1 viruses. A 71-year-old man with polycythemia vera who was in the same ward as the index case-patient for 6 days acquired infection with H7N9 and pH1N1 viruses. The incubation period for the second case-patient was estimated to be <4 days. Both case-patients died of multiple organ failure. Virus genetic sequences from the 2 case-patients were identical. Of 103 close contacts, none had acute respiratory symptoms; all were negative for H7N9 virus. Serum samples from both case-patients demonstrated strong proinflammatory cytokine secretion but incompetent protective immune responses. These findings strongly suggest limited nosocomial co-transmission of H7N9 and pH1N1 viruses from 1 immunocompromised patient to another. PMID:26982379

Evolution and characterisation of the AhRAF4 NB-ARC gene family induced by Aspergillus flavus inoculation and abiotic stresses in peanut.

PubMed

Deng, Y; Chen, H; Zhang, C; Cai, T; Zhang, B; Zhou, S; Fountain, J C; Pan, R-L; Guo, B; Zhuang, W-J

2018-03-30

Aflatoxin contamination in peanut is a serious food safety issue to human health around the world. Finding disease resistance genes is a key strategy for genetic improvement in breeding to deal with this issue. We identified an Aspergillus flavus-induced NBS-LRR gene, AhRAF4, using a microarray-based approach. By comparison of 23 sequences from three species using phytogenetics, protein secondary structure and three-dimensional structural analyses, AhRAF4 was revealed to be derived from Arachis duranensis by recombination, and has newly evolved into a family of several members, characterised by duplications and point mutations. However, the members of the family descended from A. ipaensis were lost following tetraploidisation. AhRAF4 was slightly up-regulated by low temperature, drought, salicylic acid and ethylene, but down-regulated by methyl jasmonate. The distinct responses upon As. flavus inoculation and the differential reactions between resistant and susceptible varieties indicate that AhRAF4 might play a role in defence responses. Temporal and spatial expression and the phenotype of transformed protoplasts suggest that AhRAF4 may also be associated with pericarp development. Because tetraploid cultivated peanuts are vulnerable to many pathogens, an exploration of R-genes may provide an effective method for genetic improvement of peanut cultivars. © 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

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.

PubMed

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation.

PubMed

Liu, Yuying; Liang, Xiaoyu; Dong, Wenqian; Fang, Yi; Lv, Jiadi; Zhang, Tianzhen; Fiskesund, Roland; Xie, Jing; Liu, Jinyan; Yin, Xiaonan; Jin, Xun; Chen, Degao; Tang, Ke; Ma, Jingwei; Zhang, Huafeng; Yu, Jing; Yan, Jun; Liang, Huaping; Mo, Siqi; Cheng, Feiran; Zhou, Yabo; Zhang, Haizeng; Wang, Jing; Li, Jingnan; Chen, Yang; Cui, Bing; Hu, Zhuo-Wei; Cao, Xuetao; Xiao-Feng Qin, F; Huang, Bo

2018-03-12

Despite the clinical successes fostered by immune checkpoint inhibitors, mechanisms underlying PD-1 upregulation in tumor-infiltrating T cells remain an enigma. Here, we show that tumor-repopulating cells (TRCs) drive PD-1 upregulation in CD8 + T cells through a transcellular kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway. Interferon-γ produced by CD8 + T cells stimulates release of high levels of Kyn produced by TRCs, which is transferred into adjacent CD8 + T cells via the transporters SLC7A8 and PAT4. Kyn induces and activates AhR and thereby upregulates PD-1 expression. This Kyn-AhR pathway is confirmed in both tumor-bearing mice and cancer patients and its blockade enhances antitumor adoptive T cell therapy efficacy. Thus, we uncovered a mechanism of PD-1 upregulation with potential tumor immunotherapeutic applications. Copyright © 2018 Elsevier Inc. All rights reserved.

An outbreak of influenza A(H1N1)pdm09 virus in a primary school in Vietnam.

PubMed

Duong, Tran Nhu; Tho, Nguyen Thi Thi; Hien, Nguyen Tran; Olowokure, Babatunde

2015-10-15

Despite school pupils being at greatest risk during the 2009 influenza pandemic there are limited data on outbreaks of influenza A(H1N1)pdm09 in primary schools in South-East Asia. This prospective cohort study describes an outbreak of influenza A(H1N1)pdm09 in a primary school in rural Vietnam. In total 103 cases of influenza-like illness were found among the 407 pupils in the primary school. Ten of these were laboratory confirmed cases of influenza A(H1N1)pdm09 virus. The overall attack rate (AR) was 25% (103/407), and was highest (41%) in grade 4 pupils, where the outbreak started. All cases in the outbreak presented with a mild and self-limiting illness, acute respiratory symptoms and fever. Public health interventions to contain the outbreak could explain the lower attack rates in other grades. Ill pupils were asked to stay at home. Oseltamivir was not given to pupils and the school did not close during the outbreak. The last detected case occurred 12 days following identification of the first case. This is the first report of an outbreak of influenza A(H1N1)pdm09 among pupils in a primary school in Vietnam. High attack rates in Grade 4 pupils suggest shared activities contributed to transmission. The public health response using non-pharmaceutical measures may have played a role in ending the outbreak.

Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

PubMed

Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

2016-09-01

We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

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

PubMed

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

Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases

PubMed Central

Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; de Melo, Maria Elisabeth Lisboa; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; da Silva, Luciene Alexandre Bié; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

2016-01-01

Abstract We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

High doses of recombinant mannan-binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC-SIGN.

PubMed

Yu, Lei; Shang, Shiqiang; Tao, Ran; Wang, Caiyun; Zhang, Li; Peng, Hao; Chen, Yinghu

2017-07-01

The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human health. Low doses of mannan-binding lectin (MBL) (<1 μg/mL) were shown not to protect against influenza A(H1N1)pdm09 infection. However, the effect of high doses of MBL has not been investigated. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell line, THP-1. High doses of recombinant or human MBL inhibited binding of influenza A(H1N1)pdm09 to both these cell types in the presence of complement derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells. This study demonstrates that high doses of MBL can inhibit binding of influenza A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our results suggest that DC-SIGN may be an alternative receptor for influenza A(H1N1)pdm09 virus. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Influenza A(H5N8) virus isolation in Russia, 2014.

PubMed

Marchenko, Vasiliy Y; Susloparov, Ivan M; Kolosova, Nataliya P; Goncharova, Nataliya I; Shipovalov, Andrey V; Durymanov, Alexander G; Ilyicheva, Tatyana N; Budatsirenova, Lubov V; Ivanova, Valentina K; Ignatyev, Georgy A; Ershova, Svetlana N; Tulyahova, Valeriya S; Mikheev, Valeriy N; Ryzhikov, Alexander B

2015-11-01

In this study, we report the isolation of influenza A(H5N8) virus from a Eurasian wigeon (Anas penelope) in Sakha Republic of the Russian Far East. The strain A/wigeon/Sakha/1/2014 (H5N8) has been shown to be pathogenic for mammals. It is similar to the strains that caused outbreaks in wild birds and poultry in Southeast Asia and Europe in 2014.

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

PubMed

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.

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

PubMed

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

2016-07-25

The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3·H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7-carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Distribution of gene segments of the pandemic A(H1N1) 2009 virus lineage in pig populations.

PubMed

Okuya, K; Matsuu, A; Kawabata, T; Koike, F; Ito, M; Furuya, T; Taneno, A; Akimoto, S; Deguchi, E; Ozawa, M

2018-05-06

Swine influenza viruses (SIVs) are important not only for pig farming, but also for public health. In fact, pandemic A(H1N1) 2009 viruses [A(H1N1)pdm09] were derived from SIVs. Therefore, timely characterization of locally circulating SIVs is necessary for understanding the global status of SIVs. To genetically characterize SIVs circulating in Japanese pig populations, we isolated 24 SIVs of three subtypes (17 H1N1, four H1N2 and three H3N2 strains) from 14 pig farms in Japan from 2013 to 2016. Genetic analyses revealed that the haemagglutinin (HA) and neuraminidase (NA) genes of the 17 H1N1 and the HA gene of one H1N2, A/swine/Aichi/02/2016 (H1N2), SIVs belonged to the A(H1N1)pdm09 lineage. More importantly, all of the remaining six gene segments (i.e., PB1, PB1, PA, NP, M and NS) of the 24 SIVs, regardless of the HA and NA subtype, were also classified as belonging to the A(H1N1)pdm09 lineage. These results indicate that gene segments of A(H1N1)pdm09 lineage are widely distributed in SIVs circulating in Japanese pig populations In addition, the NA gene of A/swine/Aichi/02/2016 (H1N2) shared less than 88.5% nucleotide identity with that of the closest relative A/swine/Miyagi/5/2003 (H1N2), which was isolated in Japan in 2003. These results indicate the sustained circulation of classical H1N2-derived SIVs with remarkable diversity in the NA genes in Japanese pig populations. These findings highlight the necessity of both intensive biosecurity systems and active SIV surveillance in pig populations worldwide for both animal and public health. © 2018 Blackwell Verlag GmbH.

Melanization and Pathogenicity in the Insect, Tenebrio molitor, and the Crustacean, Pacifastacus leniusculus, by Aeromonas hydrophila AH-3

PubMed Central

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

2010-01-01

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

SLC6A19 is a novel putative gene, induced by dioxins via AhR in human hepatoma HepG2 cells.

PubMed

Tian, Wenjing; Fu, Hualing; Xu, Tuan; Xu, Sherry Li; Guo, Zhiling; Tian, Jijing; Tao, Wuqun; Xie, Heidi Qunhui; Zhao, Bin

2018-06-01

The aryl hydrocarbon receptor (AhR) plays an important role in mediating dioxins toxicity. Currently, genes of P450 families are major research interests in studies on AhR-mediated gene alterations caused by dioxins. Genes related to other metabolic pathways or processes may be also responsive to dioxin exposures. Amino acid transporter B0AT1 (encoded by SLC6A19) plays a decisive role in neutral amino acid transport which is present in kidney, intestine and liver. However, effects of dioxins on its expression are still unknown. In the present study, we focused on the effects of dioxin and dioxin-like compounds on SLC6A19 expression in HepG2 cells. We identified SLC6A19 as a novel putative target gene of AhR activation in HepG2 cells. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) increased the expression of SLC6A19 in time- and concentration-dependent manners. Using AhR antagonist CH223191 and/or siRNA assays, we demonstrated that certain AhR agonists upregulated SLC6A19 expression via AhR, including TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD), 2,3,4,7,8- pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and PCB126. In addition, the expression of B0AT1 was also significantly induced by TCDD in HepG2 cells. Our study suggested that dioxins might affect the transcription and translation of SLC6A19 in HepG2 cells, which might be a novel putative gene to assess dioxins' toxicity in amino acid transport and metabolism in liver. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.

PubMed

Flannery, Brendan; Smith, Catherine; Garten, Rebecca J; Levine, Min Z; Chung, Jessie R; Jackson, Michael L; Jackson, Lisa A; Monto, Arnold S; Martin, Emily T; Belongia, Edward A; McLean, Huong Q; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard; Nowalk, Mary Patricia; Griffin, Marie R; Keipp Talbot, H; Treanor, John J; Wentworth, David E; Fry, Alicia M

2018-06-20

The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 × [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Whole-Genome Sequence of Aeromonas hydrophila Strain AH-1 (Serotype O11)

PubMed Central

Forn-Cuní, Gabriel; Tomás, Juan M.

2016-01-01

Aeromonas hydrophila is an emerging pathogen of aquatic and terrestrial animals, including humans. Here, we report the whole-genome sequence of the septicemic A. hydrophila AH-1 strain, belonging to the serotype O11, and the first mesophilic Aeromonas with surface layer (S-layer) to be sequenced. PMID:27587829

Molecular and epidemiological analysis of pandemic and post-pandemic influenza A(H1N1)pdm09 virus from central India.

PubMed

Sahu, Mahima; Singh, Neeru; Shukla, Mohan K; Potdar, Varhsa A; Sharma, Ravendra K; Sahare, Lalit Kumar; Ukey, Mahendra J; Barde, Pradip V

2018-03-01

Influenza A(H1N1)pdm09 virus pandemic struck India in 2009 and continues to cause outbreaks in its post-pandemic phase. Diminutive information is available about influenza A(H1N1)pdm09 from central India. This observational study presents epidemiological and molecular findings for the period of 6 years. Throat swab samples referred from districts of Madhya Pradesh were subjected to diagnosis of influenza A(H1N1)pdm09 following WHO guidelines. Clinical and epidemiological data were recorded and analyzed. Hemagglutinin (HA) gene sequencing and phylogenetic analysis were performed. The H275Y mutation responsible for antiviral resistance was tested using allelic real-time RT-PCR. Out of 7365 tested samples, 2406 (32.7%) were positive for influenza A(H1N1)pdm09, of which 363 (15.08%) succumbed to infection. Significant trends were observed in positivity (χ 2  = 50.8; P < 0.001) and mortality (χ 2  = 24.4; P < 0.001) with increasing age. Mutations having clinical and epidemiological importance were detected. Phylogenetic analysis of HA gene sequences revealed that clade 7, 6A, and 6B viruses were in circulation. Oseltamivir resistance was detected in three fatal cases. Influenza A(H1N1)pdm09 viruses having genetic diversity were detected from central India and continues to be a concern for public health. This study highlights the need of year-round monitoring by establishment of strong molecular and clinical surveillance program. © 2017 Wiley Periodicals, Inc.

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

PubMed

Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S

2016-09-01

Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

Cloning and Characterization of 5′ Flanking Regulatory Sequences of AhLEC1B Gene from Arachis Hypogaea L.

PubMed Central

Tang, Guiying; Xu, Pingli; Liu, Wei; Liu, Zhanji; Shan, Lei

2015-01-01

LEAFY COTYLEDON1 (LEC1) is a B subunit of Nuclear Factor Y (NF-YB) transcription factor that mainly accumulates during embryo development. We cloned the 5′ flanking regulatory sequence of AhLEC1B gene, a homolog of Arabidopsis LEC1, and analyzed its regulatory elements using online software. To identify the crucial regulatory region, we generated a series of GUS expression frameworks driven by different length promoters with 5′ terminal and/or 3′ terminal deletion. We further characterized the GUS expression patterns in the transgenic Arabidopsis lines. Our results show that both the 65bp proximal promoter region and the 52bp 5′ UTR of AhLEC1B contain the key motifs required for the essential promoting activity. Moreover, AhLEC1B is preferentially expressed in the embryo and is co-regulated by binding of its upstream genes with both positive and negative corresponding cis-regulatory elements. PMID:26426444

Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

PubMed

Maldonado-Gómez, María X; Martínez, Inés; Bottacini, Francesca; O'Callaghan, Amy; Ventura, Marco; van Sinderen, Douwe; Hillmann, Benjamin; Vangay, Pajau; Knights, Dan; Hutkins, Robert W; Walter, Jens

2016-10-12

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution. Copyright © 2016 Elsevier Inc. All rights reserved.

Swine-to-Human Transmission of Influenza A(H3N2) Virus at Agricultural Fairs, Ohio, USA, 2012

PubMed Central

Nelson, Sarah W.; Page, Shannon L.; Nolting, Jacqueline M.; Killian, Mary L.; Sreevatsan, Srinand; Slemons, Richard D.

2014-01-01

Agricultural fairs provide an opportunity for bidirectional transmission of influenza A viruses. We sought to determine influenza A virus activity among swine at fairs in the United States. As part of an ongoing active influenza A virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected Ohio agricultural fairs during 2012. Influenza A(H3N2) virus was isolated from swine at 10 of the fairs. According to a concurrent public health investigation, 7 of the 10 fairs were epidemiologically linked to confirmed human infections with influenza A(H3N2) variant virus. Comparison of genome sequences of the subtype H3N2 isolates recovered from humans and swine from each fair revealed nucleotide identities of >99.7%, confirming zoonotic transmission between swine and humans. All influenza A(H3N2) viruses isolated in this study, regardless of host species or fair, were >99.5% identical, indicating that 1 virus strain was widely circulating among exhibition swine in Ohio during 2012. PMID:25148572

Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report.

PubMed

Iadevaia, Carlo; Iacotucci, Paola; Carnovale, Vincenzo; Calabrese, Cecilia; Rea, Gaetano; Ferrara, Nicola; Perrotta, Fabio; Mazzarella, Gennaro; Bianco, Andrea

2017-10-01

Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes. We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013–2014 in the United States

PubMed Central

Gaglani, Manjusha; Pruszynski, Jessica; Murthy, Kempapura; Clipper, Lydia; Robertson, Anne; Reis, Michael; Chung, Jessie R.; Piedra, Pedro A.; Avadhanula, Vasanthi; Nowalk, Mary Patricia; Zimmerman, Richard K.; Jackson, Michael L.; Jackson, Lisa A.; Petrie, Joshua G.; Ohmit, Suzanne E.; Monto, Arnold S.; McLean, Huong Q.; Belongia, Edward A.; Fry, Alicia M.; Flannery, Brendan

2016-01-01

Background. The predominant strain during the 2013–2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. Methods. The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2–17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. Results. We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR–confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%–61%). Among fully vaccinated children aged 2–17 years, the effectiveness of LAIV4 was 17% (95% CI, −39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%–74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. Conclusions. During 2013–2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States. PMID:26743842

In vitro evaluation of the contact angle formed between AH Plus, Hybrid Root Seal and mineral trioxide aggregate Plus sealer with dentin and gutta-percha.

PubMed

Nikhil, Vineeta; Jaiswal, Shikha; Bajpai, Gauravi

2018-01-01

The purpose of this study was evaluation and comparison of the contact angle of new root canal sealers - Hybrid Root Seal, mineral trioxide aggregate (MTA) Plus, and the conventional AH Plus sealer with dentin and gutta-percha. Two groups (Group D - dentin and Group G - gutta-percha) of 18 samples each were further randomly divided into 3 subgroups based on the type of sealer used, that is, AH Plus, Hybrid Root Seal, and MTA Plus. Contact angle measurement device (Phoenix 300) was used to measure the contact angle of the sealers on both dentin and gutta-percha. The results thus obtained were analyzed using one-way analysis of variance and Student's t -test. MTA Plus recorded significantly higher values of contact angle on both the substrates, that is, dentin and gutta-percha when compared to AH Plus and Hybrid root canal sealer. The lowest value of contact angle in gutta-percha and dentin was shown by Hybrid root canal sealer and AH Plus, respectively. Both AH Plus and Hybrid Root Seal exhibited lower contact angle values, and hence, better wettability on both dentin and gutta-percha as compared to MTA Plus.

Highly pathogenic avian influenza A(H7N9) virus, Tennessee, USA, March 2017

USDA-ARS?s Scientific Manuscript database

In March 2017, highly pathogenic avian influenza A(H7N9) was detected at 2 poultry farms in Tennessee, USA. Surveillance data and genetic analyses indicated multiple introductions of low pathogenicity avian influenza virus before mutation to high pathogenicity and interfarm transmission. Poultry sur...

Evaluation of 20 Ah Li Ion Cells

NASA Technical Reports Server (NTRS)

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.

Validation test of 125 Ah advanced design IPV nickel-hydrogen flight cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1993-01-01

An update of validation test results confirming the advanced design nickel-hydrogen cell is presented. An advanced 125 Ah individual pressure vessel Ni-H cell was designed. The primary function of the advanced cell is to store and deliver energy for long-term LEO spacecraft missions. The new features of this design are: (1) use of 26 percent rather than 31 percent KOH electrolyte; (2) use of a patented catalyzed wall wick; (3) use of serrated-edge separators to facilitate gaseous O and H flow within the cell, while maintaining physical contact with the wall wick for electrolyte management; and (4) use of a floating rather than a fixed stack to accommodate Ni electrode expansion due to charge/discharge cycling. The significant improvements resulting from these innovations are extended cycle life; enhanced thermal, electrolyte, and oxygen management; and accommodation of Ni electrode expansion. Six 125 Ah flight cells based on this design were fabricated; the catalyzed wall wick cells have been cycled for over 19,000 cycles with no cell failures in the continuing test. Two of the noncatalyzed wall wick cells failed (cycles 9588 and 13,900).

Genomic signature analysis of the recently emerged highly pathogenic A(H5N8) avian influenza virus: implying an evolutionary trend for bird-to-human transmission.

PubMed

Xu, Wei; Dai, Yanyan; Hua, Chen; Wang, Qian; Zou, Peng; Deng, Qiwen; Jiang, Shibo; Lu, Lu

2017-12-01

In early 2014, a novel subclade (2.3.4.4) of the highly pathogenic avian influenza (HPAI) A(H5N8) virus caused the first outbreak in domestic ducks and migratory birds in South Korea. Since then, it has spread to 44 countries and regions. To date, no human infections with A(H5N8) virus have been reported, but the possibility cannot be excluded. By analyzing the genomic signatures of A(H5N8) strains, we found that among the 47 species-associated signature positions, three positions exhibited human-like signatures (HLS), including PA-404S, PB2-613I and PB2-702R and that mutation trend of host signatures of avian A(H5N8) is different before and after 2014. About 82% of A(H5N8) isolates collected after January of 2014 carried the 3 HLS (PA-404S/PB2-613I/PB2-702R) in combination, while none of isolates collected before 2014 had this combination. Furthermore, the HA protein had S137A and S227R substitutions in the receptor-binding site and A160T in the glycosylation site, potentially increasing viral ability to bind human-type receptors. Based on these findings, the newly emerged HPAI A(H5N8) isolates show an evolutionary trend toward gaining more HLS and, along with it, the potential for bird-to-human transmissibility. Therefore, more extensive surveillance of this rapidly spreading HPAI A(H5N8) and preparedness against its potential pandemic are urgently needed. Copyright © 2017. Published by Elsevier Masson SAS.

Genetic drift of influenza A(H3N2) viruses during two consecutive seasons in 2011-2013 in Corsica, France.

PubMed

Fantoni, Anais; Arena, Christophe; Corrias, Laura; Salez, Nicolas; de Lamballerie, Xavier Nicolas; Amoros, Jean Pierre; Blanchon, Thierry; Varesi, Laurent; Falchi, Alessandra

2014-04-01

The 2011-2012 and 2012-2013 post-pandemic influenza outbreaks were characterized by variability in the A(H3N2) influenza viruses, resulting in low to moderate vaccine effectiveness (VE). The aim of this study was to investigate the molecular evolution and vaccine strain match of the A(H3N2) influenza viruses, having been circulated throughout the population of the French Corsica Island in 2011-2012 and again in 2012-2013. Clinical samples from 31 patients with confirmed A(H3N2) influenza viruses were collected by general practitioners (GPs) over these two consecutive seasons. An analysis of genetic distance and antigenic drift was conducted. Based on a hemagglutinin (HA) aminoacid sequence analysis, the Corsican A(H3N2) viruses fell into the A/Victoria/208/2009 genetic clade, group 3. All influenza viruses were characterized by at least four fixed amino acid mutations which were: N145S (epitope A); Q156H and V186G (epitope B) Y219S (epitope D), with respect to the A/Perth/16/2009 (reference vaccine strain for the 2011-2012) and the A/Victoria/361/2011 (reference vaccine strain for the 2012-2013). Using the p(epitope) model, the percentages of the perfect match VE estimated against circulated strains declined within and between seasons, with estimations of <50%. Overall, these results seem to indicate an antigenic drift of the A(H3N2) influenza viruses which were circulated in Corsica. These findings highlight the importance of the continuous and careful surveillance of genetic changes in the HA domain during seasonal influenza epidemics, in order to provide information on newly emerging genetic variants. © 2013 Wiley Periodicals, Inc.

Field Trial on a Rack-mounted DC Power Supply System with 80-Ah Lithium-ion Batteries

NASA Astrophysics Data System (ADS)

Matsushima, Toshio

Using an industrial lithium-ion battery that has higher energy density than conventional valve-regulated lead-acid batteries, a rack-mounted DC-power-supply system was assembled and tested at a base transceiver station (BTS) offering actual services. A nominal output voltage and maximum output current of the system is 53.5V and 20A, respectively. An 80-Ah lithium-ion battery composed of 13 cells connected in series was applied in the system and maintained in a floating charge method. The DC-power-supply system was installed in a 19-inch power rack in the telecommunications equipment box at BTS. The characteristics of the 80Ah lithium-ion battery, specifications of the DC-power-supply system and field-test results were shown in this paper.

Genetic Diversity of Highly Pathogenic Avian Influenza A(H5N8/H5N5) Viruses in Italy, 2016–17

PubMed Central

Monne, Isabella; Mulatti, Paolo; Zecchin, Bianca; Bonfanti, Lebana; Ormelli, Silvia; Milani, Adelaide; Cecchettin, Krizia; Lemey, Philippe; Moreno, Ana; Massi, Paola; Dorotea, Tiziano; Marangon, Stefano; Terregino, Calogero

2017-01-01

In winter 2016–17, highly pathogenic avian influenza A(H5N8) and A(H5N5) viruses of clade 2.3.4.4 were identified in wild and domestic birds in Italy. We report the occurrence of multiple introductions and describe the identification in Europe of 2 novel genotypes, generated through multiple reassortment events. PMID:28661831

Lack of evidence for pre‐symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009

PubMed Central

Hermes, Julia; Bernard, Helen; Buchholz, Udo; Spackova, Michaela; Löw, Johann; Loytved, Gunther; Suess, Thorsten; Hautmann, Wolfgang; Werber, Dirk

2011-01-01

Please cite this paper as: Hermes et al. (2011) Lack of evidence for pre‐symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009. Influenza and Other Respiratory Viruses 5(6), e499–e503. Background  Observations on the role of pre‐symptomatic transmission in the spread of influenza virus are scanty. In June 2009, an outbreak of pandemic A(H1N1) 2009 infection occurred at a teenager’s party in Germany. The objective of this study was to identify risk factors for pandemic A(H1N1) 2009 infection. Methods  We performed a retrospective cohort study among party guests. A case was defined as pandemic A(H1N1) 2009 infection confirmed by rRT‐PCR who developed influenza‐like illness between 1 and 5 June 2009. Contact patterns among party guests were evaluated. Results  In eight (36%) of 27 party guests, the outcome was ascertained. A travel returnee from a country with endemic pandemic A(H1N1) 2009 who fell ill toward the end of the party was identified as the source case. Party guests with pandemic A(H1N1) 2009 infection had talked significantly longer to the source case than non‐infected persons (P‐value: 0·001). Importantly, none (0/9) of those who had left the party prior to the source case’s symptom onset became infected compared to 7 (41%) of 17 who stayed overnight (P = 0·06), and these persons all had transmission‐prone contacts to the source case. Conclusions  In this outbreak with one index case, there was no evidence to support pre‐symptomatic transmission of pandemic A(H1N1) 2009. Further evidence is required, ideally from larger studies with multiple index cases, to more accurately characterize the potential for pre‐symptomatic transmission of influenza virus. PMID:21668675

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

PubMed

Tang, Juan; Song, Meiyan; Watanabe, Gen; Nagaoka, Kentaro; Rui, Xiaoli; Li, ChunMei

2016-09-01

4-Nitrophenol (PNP) is a persistent organic pollutant that was proven to be an environmental endocrine disruptor. The aim of this study was to evaluate the role of the estrogen receptor-α (ER-α) and aryl hydrocarbon receptor (AhR) signaling pathway in regulating the damage response to PNP in the small intestine of rats. Wistar-Imamichi male rats (21 d) were randomly divided into two groups: the control group and PNP group. Each group had three processes that were gavaged with PNP or vehicle daily: single dose (1 d), repeated dose (3 consecutive days) (3 d), and repeated dose with recovery (3 consecutive days and 3 recovery days) (6 d). The weight of the body, the related viscera, and small intestine were examined. Histological parameters of the small intestine and the quantity of mucus proteins secreted by small goblet cells were determined using HE staining and PAS staining. The mRNA expression of AhR, ER-α, CYP1A1, and GST was measured by real-time qPCR. In addition, we also analyzed the AhR, ER-α, and CYP1A1 expression in the small intestine by immunohistochemical staining. The small intestines histologically changed in the PNP-treated rat and the expression of AhR, CYP1A1, and GST was increased. While ER-α was significantly decreased in the small intestine, simultaneously, when rats were exposed to a longer PNP treatment, the damages disappeared. Our results demonstrate that PNP has an effect on the expression of AhR signaling pathway genes, AhR, CYP1A1, and GST, and ER-α in the rat small intestine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lithium-Ion Performance and Abuse Evaluation Using Lithium Technologies 9Ah cell

NASA Technical Reports Server (NTRS)

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.

Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015.

PubMed

Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi; Li, Junhua; Shu, Yuelong

2016-11-01

In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.

Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015

PubMed Central

Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi

2016-01-01

In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans. PMID:27767007

Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines

PubMed Central

Kamenickova, Alzbeta; Anzenbacherova, Eva; Pavek, Petr; Soshilov, Anatoly A.; Denison, Michael S.; Zapletalova, Michaela; Anzenbacher, Pavel; Dvorak, Zdenek

2013-01-01

Anthocyanins are plant pigments occurring in flowers and berry fruits. Since a phenomenon of food-drug interactions is increasingly emerging, we examined the effects of 21 major anthocyanins and the extracts from 3 food supplements containing anthocyanins on the aryl hydrocarbon receptor (AhR) – cytochrome P450 CYP1A1 signaling pathway in human hepatocytes and human hepatic HepG2 and intestinal LS174T cancer cells. Pelargonidin-3-O-rutinoside (PEL-2) and cyanidin-3,5-O-diglucoside (CYA-3) dose-dependently activated AhR, as revealed by gene reporter assay. PEL-2 and CYA-3 induced CYP1A1 mRNA but not protein in HepG2 and LS174T cells. Neither compound induced CYP1A1 mRNA and protein in four different primary human hepatocytes cultures. The effects of PEL-2 and CYA-3 on AhR occurred by ligand-dependent and ligand-independent mechanisms, respectively, as demonstrated by ligand binding assay. In a direct enzyme inhibition assay, none of the antocyanins tested inhibited the CYP1A1 marker activity to less than 50% even at 100 µM concentration. PEL-2 and CYA-3 at 100 µM inhibited CYP1A1 to 79% and 65%, respectively. In conclusion, with exception of PEL-2 and CYA-3, there were no effects of 19 major anthocyanins and 3 food supplements containing anthocyanins on AhR-CYP1A1 signaling, implying zero potential of these compounds for food-drug interactions with respect to AhR-CYP1A1 pathway. PMID:23735880

Real-Time Station Grouping under Dynamic Traffic for IEEE 802.11ah

PubMed Central

Tian, Le; Latré, Steven

2017-01-01

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

Real-Time Station Grouping under Dynamic Traffic for IEEE 802.11ah.

PubMed

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

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

PubMed Central

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

Seroprevalence of Antibodies against Seal Influenza A(H10N7) Virus in Harbor Seals and Gray Seals from the Netherlands.

PubMed

Bodewes, Rogier; Rubio García, Ana; Brasseur, Sophie M; Sanchez Conteras, Guillermo J; van de Bildt, Marco W G; Koopmans, Marion P G; Osterhaus, Albert D M E; Kuiken, Thijs

2015-01-01

In the spring and summer 2014, an outbreak of seal influenza A(H10N7) virus infection occurred among harbor seals (Phoca vitulina) off the coasts of Sweden and Denmark. This virus subsequently spread to harbor seals off the coasts of Germany and the Netherlands. While thousands of seals were reported dead in Sweden, Denmark and Germany, only a limited number of seals were found dead in the Netherlands. To determine the extent of exposure of seals in the Netherlands to influenza A/H10N7 virus, we measured specific antibody titers in serum samples from live-captured seals and seals admitted for rehabilitation in the Netherlands by use of a hemagglutination inhibition assay and an ELISA. In harbor seals in 2015, antibodies against seal influenza A(H10N7) virus were detected in 41% (32 out of 78) pups, 10% (5 out of 52) weaners, and 58% (7 out of 12) subadults or adults. In gray seals (Halichoerus grypus) in 2015, specific antibodies were not found in the pups (n = 26), but in 26% (5 out of 19) of the older animals. These findings indicate that, despite apparent low mortality, infection with seal influenza A(H10N7) virus was geographically widespread and also occurred in grey seals.

Lack of evidence for pre-symptomatic transmission of pandemic influenza virus A(H1N1) 2009 in an outbreak among teenagers; Germany, 2009.

PubMed

Hermes, Julia; Bernard, Helen; Buchholz, Udo; Spackova, Michaela; Löw, Johann; Loytved, Gunther; Suess, Thorsten; Hautmann, Wolfgang; Werber, Dirk

2011-11-01

Observations on the role of pre-symptomatic transmission in the spread of influenza virus are scanty. In June 2009, an outbreak of pandemic A(H1N1) 2009 infection occurred at a teenager's party in Germany. The objective of this study was to identify risk factors for pandemic A(H1N1) 2009 infection. We performed a retrospective cohort study among party guests. A case was defined as pandemic A(H1N1) 2009 infection confirmed by rRT-PCR who developed influenza-like illness between 1 and 5 June 2009. Contact patterns among party guests were evaluated. In eight (36%) of 27 party guests, the outcome was ascertained. A travel returnee from a country with endemic pandemic A(H1N1) 2009 who fell ill toward the end of the party was identified as the source case. Party guests with pandemic A(H1N1) 2009 infection had talked significantly longer to the source case than non-infected persons (P-value: 0·001). Importantly, none (0/9) of those who had left the party prior to the source case's symptom onset became infected compared to 7 (41%) of 17 who stayed overnight (P = 0·06), and these persons all had transmission-prone contacts to the source case. In this outbreak with one index case, there was no evidence to support pre-symptomatic transmission of pandemic A(H1N1) 2009. Further evidence is required, ideally from larger studies with multiple index cases, to more accurately characterize the potential for pre-symptomatic transmission of influenza virus. © 2011 Blackwell Publishing Ltd.

Structural Integrity Recording System (SIRS) for U.S. Army AH-1S Helicopters.

DTIC Science & Technology

1981-03-01

October 1977 - October 1980 Approved for public release; distribution unlimited.I Prepared for SAPPLIED TECHNOLOGY LABORATORYBU. S. ARMY RESEARCH AND... 1980 ................205 5 LIST OF ILLUSTRATIONS Figure Page 1 AH-lS Helicopter Instrumentation Functional Block Diagram ..... ............... ... 19 2...flight times frequently indicated numerous discrepancies during the data collection time span from February 1979 to January 1980 . The symptoms

Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic - China, October 2016-February 2017.

PubMed

Iuliano, A Danielle; Jang, Yunho; Jones, Joyce; Davis, C Todd; Wentworth, David E; Uyeki, Timothy M; Roguski, Katherine; Thompson, Mark G; Gubareva, Larisa; Fry, Alicia M; Burns, Erin; Trock, Susan; Zhou, Suizan; Katz, Jacqueline M; Jernigan, Daniel B

2017-03-10

During March 2013-February 24, 2017, annual epidemics of avian influenza A(H7N9) in China resulted in 1,258 avian influenza A(H7N9) virus infections in humans being reported to the World Health Organization (WHO) by the National Health and Family Planning Commission of China and other regional sources (1). During the first four epidemics, 88% of patients developed pneumonia, 68% were admitted to an intensive care unit, and 41% died (2). Candidate vaccine viruses (CVVs) were developed, and vaccine was manufactured based on representative viruses detected after the emergence of A(H7N9) virus in humans in 2013. During the ongoing fifth epidemic (beginning October 1, 2016),* 460 human infections with A(H7N9) virus have been reported, including 453 in mainland China, six associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one in an asymptomatic poultry worker in Macao (1). Although the clinical characteristics and risk factors for human infections do not appear to have changed (2,3), the reported human infections during the fifth epidemic represent a significant increase compared with the first four epidemics, which resulted in 135 (first epidemic), 320 (second), 226 (third), and 119 (fourth epidemic) human infections (2). Most human infections continue to result in severe respiratory illness and have been associated with poultry exposure. Although some limited human-to-human spread continues to be identified, no sustained human-to-human A(H7N9) transmission has been observed (2,3).

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

ERIC Educational Resources Information Center

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…

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

PubMed

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.

Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru

PubMed Central

Chowell, Gerardo; Viboud, Cécile; Munayco, Cesar V.; Gómez, Jorge; Simonsen, Lone; Miller, Mark A.; Tamerius, James; Fiestas, Victor; Halsey, Eric S.; Laguna-Torres, Victor A.

2011-01-01

Background Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. Methods We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. Results The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. Conclusions Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school

Estimating the Distribution of the Incubation Periods of Human Avian Influenza A(H7N9) Virus Infections.

PubMed

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

2015-10-15

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. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis.

PubMed

Abron, Jessicca D; Singh, Narendra P; Mishra, Manoj K; Price, Robert L; Nagarkatti, Mitzi; Nagarkatti, Prakash S; Singh, Udai P

2018-04-19

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. The precise etiology of IBD is unknown, but clear evidence suggests that intestinal inflammation is caused by an excessive immune response to mucosal antigens. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. In the current study, we investigated if nontoxic ligand of AhR, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), can attenuate dextran sodium sulphate (DSS)-induced colitis. Our studies demonstrated that in mice that received ITE treatment, in-vivo colitis pathogenesis, including a decrease in body weight, was significantly reversed along with the systemic and intestinal inflammatory cytokines. ITE increased the expression of Tregs in spleen, mesenteric lymph nodes (MLNs) and colon lamina propria lymphocytes (cLPL) of mice with colitis when compared to controls. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. ITE treatment also increased dendritic cells (DCs; CD11c+) and decreased F4/80+ (macrophage) from the spleen, MLNs and cLPL in mice with colitis. ITE also reversed the systemic and intestinal frequency of CD4+T cells during colitis and suppressed inflammatory cytokines including IFN-γ, TNF-α, IL-17, IL-6 and IL-1 as well as induced IL-10 levels. These findings suggest that ITE attenuates colitis through induction of Tregs and reduction in inflammatory CD4+ T cells and cytokines. Thus, our work demonstrates that the nontoxic endogenous AhR ligand ITE, may serve as a therapeutic modality to treat IBD.

Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany†

PubMed Central

Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte

2014-01-01

Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531

Retrospective Investigation of an Influenza A/H1N1pdm Outbreak in an Italian Military Ship Cruising in the Mediterranean Sea, May-September 2009

PubMed Central

Tarabbo, Mario; Lapa, Daniele; Castilletti, Concetta; Tommaselli, Pietro; Guarducci, Riccardo; Lucà, Giuditta; Emanuele, Alessandro; Zaccaria, Onofrio; La Gioia, Vincenzo F. P.; Girardi, Enrico; Capobianchi, Maria R.; Ippolito, Giuseppe

2011-01-01

Background Clinical surveillance may have underestimated the real extent of the spread of the new strain of influenza A/H1N1, which surfaced in April 2009 originating the first influenza pandemic of the 21st century. Here we report a serological investigation on an influenza A/H1N1pdm outbreak in an Italian military ship while cruising in the Mediterranean Sea (May 24-September 6, 2009). Methods The contemporary presence of HAI and CF antibodies was used to retrospectively estimate the extent of influenza A/H1N1pdm spread across the crew members (median age: 29 years). Findings During the cruise, 2 crew members fulfilled the surveillance case definition for influenza, but only one was laboratory confirmed by influenza A/H1N1pdm-specific RT-PCR; 52 reported acute respiratory illness (ARI) episodes, and 183 reported no ARI episodes. Overall, among the 211 crew member for whom a valid serological result was available, 39.3% tested seropositive for influenza A/H1N1pdm. The proportion of seropositives was significantly associated with more crowded living quarters and tended to be higher in those aged <40 and in those reporting ARI or suspected/confirmed influenza A/H1N1pdm compared to the asymptomatic individuals. No association was found with previous seasonal influenza vaccination. Conclusions These findings underline the risk for rapid spread of novel strains of influenza A in confined environment, such as military ships, where crowding, rigorous working environment, physiologic stress occur. The high proportion of asymptomatic infections in this ship-borne outbreak supports the concept that serological surveillance in such semi-closed communities is essential to appreciate the real extent of influenza A/H1N1pdm spread and can constitute, since the early stage of a pandemic, an useful model to predict the public health impact of pandemic influenza and to establish proportionate and effective countermeasures. PMID:21283749

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

PubMed

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.

TCDD and a Putative Endogenous AhR Ligand, ITE, Elicit the Same Immediate Changes in Gene Expression in Mouse Lung Fibroblasts

PubMed Central

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

2010-01-01

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 0.5μM 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. PMID:19933214

Clinical efficacy of seasonal influenza vaccination: characteristics of two outbreaks of influenza A(H1N1) in immunocompromised patients.

PubMed

Helanterä, I; Janes, R; Anttila, V-J

2018-06-01

Influenza A(H1N1) causes serious complications in immunocompromised patients. The efficacy of seasonal vaccination in these patients has been questioned. To describe two outbreaks of influenza A(H1N1) in immunocompromised patients. Two outbreaks of influenza A(H1N1) occurred in our institution: on the kidney transplant ward in 2014 including patients early after kidney or simultaneous pancreas-kidney transplantation, and on the oncology ward in 2016 including patients receiving chemotherapy for malignant tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal influenza vaccination were analysed. Altogether 86 patients were exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal influenza vaccination status was unknown in 10. Only three out of 38 vaccinated patients were infected with influenza A(H1N1), compared with 20 out of 38 unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients was associated with influenza, compared with seven out of 38 unvaccinated patients (P = 0.06). Shared factors behind the two outbreaks included outdated facilities not designed for the treatment of immunosuppressed patients. Vaccination coverage among patients was low, between 40% and 70% despite vaccination being offered to all patients free of charge. Vaccination coverage of healthcare workers on the transplant ward was low (46%), but, despite high coverage on the oncology ward (92%), the outbreak occurred. Seasonal influenza vaccination was clinically effective with both a reduced risk of influenza infection and a trend towards reduced mortality in these immunocompromised patients. Several possible causes were identified behind these two outbreaks, requiring continuous awareness in healthcare professionals to prevent further outbreaks. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

PubMed

Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

2016-03-01

This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

Introduction and enzootic of A/H5N1 in Egypt: Virus evolution, pathogenicity and vaccine efficacy ten years on.

PubMed

Abdelwhab, E M; Hassan, M K; Abdel-Moneim, A S; Naguib, M M; Mostafa, A; Hussein, I T M; Arafa, A; Erfan, A M; Kilany, W H; Agour, M G; El-Kanawati, Z; Hussein, H A; Selim, A A; Kholousy, S; El-Naggar, H; El-Zoghby, E F; Samy, A; Iqbal, M; Eid, A; Ibraheem, E M; Pleschka, S; Veits, J; Nasef, S A; Beer, M; Mettenleiter, T C; Grund, C; Ali, M M; Harder, T C; Hafez, H M

2016-06-01

It is almost a decade since the highly pathogenic H5N1 avian influenza virus (A/H5N1) of clade 2.2.1 was introduced to Egypt in 2005, most likely, via wild birds; marking the longest endemic status of influenza viruses in poultry outside Asia. The endemic A/H5N1 in Egypt still compromises the poultry industry, poses serious hazards to public health and threatens to become potentially pandemic. The control strategies adopted for A/H5N1 in Egyptian poultry using diverse vaccines in commercialized poultry neither eliminated the virus nor did they decrease its evolutionary rate. Several virus clades have evolved, a few of them disappeared and others prevailed. Disparate evolutionary traits in both birds and humans were manifested by accumulation of clade-specific mutations across viral genomes driven by a variety of selection pressures. Viruses in vaccinated poultry populations displayed higher mutation rates at the immunogenic epitopes, promoting viral escape and reducing vaccine efficiency. On the other hand, viruses isolated from humans displayed changes in the receptor binding domain, which increased the viral affinity to bind to human-type glycan receptors. Moreover, viral pathogenicity exhibited several patterns in different hosts. This review aims to provide an overview of the viral evolution, pathogenicity and vaccine efficacy of A/H5N1 in Egypt during the last ten years. Copyright © 2016 Elsevier B.V. All rights reserved.

Third-Generation Ah Receptor–Responsive Luciferase Reporter Plasmids: Amplification of Dioxin-Responsive Elements Dramatically Increases CALUX Bioassay Sensitivity and Responsiveness

PubMed Central

He, Guochun; Tsutsumi, Tomoaki; Zhao, Bin; Baston, David S.; Zhao, Jing; Heath-Pagliuso, Sharon; Denison, Michael S.

2011-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related dioxin-like chemicals are widespread and persistent environmental contaminants that produce diverse toxic and biological effects through their ability to bind to and activate the Ah receptor (AhR) and AhR-dependent gene expression. The chemically activated luciferase expression (CALUX) system is an AhR-responsive recombinant luciferase reporter gene–based cell bioassay that has been used in combination with chemical extraction and cleanup methods for the relatively rapid and inexpensive detection and relative quantitation of dioxin and dioxin-like chemicals in a wide variety of sample matrices. Although the CALUX bioassay has been validated and used extensively for screening purposes, it has some limitations when screening samples with very low levels of dioxin-like chemicals or when there is only a small amount of sample matrix for analysis. Here, we describe the development of third-generation (G3) CALUX plasmids with increased numbers of dioxin-responsive elements, and stable transfection of these new plasmids into mouse hepatoma (Hepa1c1c7) cells has produced novel amplified G3 CALUX cell bioassays that respond to TCDD with a dramatically increased magnitude of luciferase induction and significantly lower minimal detection limit than existing CALUX-type cell lines. The new G3 CALUX cell lines provide a highly responsive and sensitive bioassay system for the detection and relative quantitation of very low levels of dioxin-like chemicals in sample extracts. PMID:21775728

Third-generation Ah receptor-responsive luciferase reporter plasmids: amplification of dioxin-responsive elements dramatically increases CALUX bioassay sensitivity and responsiveness.

PubMed

He, Guochun; Tsutsumi, Tomoaki; Zhao, Bin; Baston, David S; Zhao, Jing; Heath-Pagliuso, Sharon; Denison, Michael S

2011-10-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related dioxin-like chemicals are widespread and persistent environmental contaminants that produce diverse toxic and biological effects through their ability to bind to and activate the Ah receptor (AhR) and AhR-dependent gene expression. The chemically activated luciferase expression (CALUX) system is an AhR-responsive recombinant luciferase reporter gene-based cell bioassay that has been used in combination with chemical extraction and cleanup methods for the relatively rapid and inexpensive detection and relative quantitation of dioxin and dioxin-like chemicals in a wide variety of sample matrices. Although the CALUX bioassay has been validated and used extensively for screening purposes, it has some limitations when screening samples with very low levels of dioxin-like chemicals or when there is only a small amount of sample matrix for analysis. Here, we describe the development of third-generation (G3) CALUX plasmids with increased numbers of dioxin-responsive elements, and stable transfection of these new plasmids into mouse hepatoma (Hepa1c1c7) cells has produced novel amplified G3 CALUX cell bioassays that respond to TCDD with a dramatically increased magnitude of luciferase induction and significantly lower minimal detection limit than existing CALUX-type cell lines. The new G3 CALUX cell lines provide a highly responsive and sensitive bioassay system for the detection and relative quantitation of very low levels of dioxin-like chemicals in sample extracts.

Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season.

PubMed

Santos, Katia Corrêa de Oliveira; Silva, Daniela Bernardes Borges da; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; Paiva, Terezinha Maria de

2017-04-03

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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 component of the vaccine for the 2016 influenza season.

AH-64 IHADSS aviator vision experiences in Operation Iraqi Freedom

NASA Astrophysics Data System (ADS)

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).

Influenza A/H1N1v in pregnancy: an investigation of the characteristics and management of affected women and the relationship to pregnancy outcomes for mother and infant.

PubMed

Yates, L; Pierce, M; Stephens, S; Mill, A C; Spark, P; Kurinczuk, J J; Valappil, M; Brocklehurst, P; Thomas, S H L; Knight, M

2010-07-01

In April 2009 a novel influenza A virus (AH1N1v) of swine origin (swine flu) emerged, spreading rapidly and achieving pandemic status in June 2009. Pregnant women were identified as being at high risk of severe influenza-related complications and as a priority group for vaccination against AH1N1v. Limited information was available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy. To assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management. Prospective national cohort studies were conducted to identify pregnant women who were (1) suspected to be infected with AH1N1v or being treated with antiviral medication in primary care; (2) vaccinated against AH1N1v; and (3) admitted to hospital with confirmed AH1N1v. Characteristics of women with influenza-like illness (ILI) in primary care were compared with those of women without symptoms accepting or declining immunisation. Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK who were uninfected with AH1N1v. Outcomes examined in hospitalised women included maternal death, admission to an intensive care unit, perinatal mortality and preterm birth. Risk factors for hospital and intensive care unit admission were examined in a full regression model. The weekly incidence of ILI among pregnant women averaged 51/100,000 over the study period. Antiviral drugs were offered to 4.8% [95% confidence interval (CI) 4.0% to 5.9%] and vaccination to 64.8% (95% CI 64.7% to 68.9%) of registered pregnant women. Ninety pregnant women with ILI presenting in primary care were reported to the research team, 55 of whom were prescribed antiviral drugs and in 42 (76%) cases this was within 2 days of symptom onset. After comparison

Risk Factors for Influenza A(H7N9) Disease in China, a Matched Case Control Study, October 2014 to April 2015

PubMed Central

Zhou, Lei; Ren, Ruiqi; Ou, Jianming; Kang, Min; Wang, Xiaoxiao; Havers, Fiona; Huo, Xiang; Liu, Xiaoqing; Sun, Qianlai; He, Yongchao; Liu, Bo; Wu, Shenggen; Wang, Yali; Sui, Haitian; Zhang, Yongjie; Tang, Shaopei; Chang, Caiyun; Xiang, Lunhui; Wang, Dong; Zhao, Shiguang; Zhou, Suizan; Chen, Tao; Xiang, Nijuan; Greene, Carolyn M.; Zhang, Yanping; Shu, Yuelong; Feng, Zijian; Li, Qun

2016-01-01

Background. Human infections with avian influenza A(H7N9) virus have been associated with exposure to poultry and live poultry markets (LPMs). We conducted a case-control study to identify additional and more specific risk factors. Methods. Cases were laboratory-confirmed A(H7N9) infections in persons in China reported from October 1, 2014 to April 30, 2015. Poultry workers, those with insufficient data, and those refusing participation were excluded. We matched up to 4 controls per case by sex, age, and residential community. Using conditional logistic regression, we examined associations between A(H7N9) infection and potential risk factors. Results. Eighty-five cases and 334 controls were enrolled with similar demographic characteristics. Increased risk of A(H7N9) infection was associated with the following: visiting LPMs (adjusted odds ratio [aOR], 6.3; 95% confidence interval [CI], 2.6–15.3), direct contact with live poultry in LPMs (aOR, 4.1; 95% CI, 1.1–15.6), stopping at a live poultry stall when visiting LPMs (aOR, 2.7; 95% CI, 1.1–6.9), raising backyard poultry at home (aOR, 7.7; 95% CI, 2.0–30.5), direct contact with backyard poultry (aOR, 4.9; 95% CI, 1.1–22.1), and having ≥1 chronic disease (aOR, 3.1; 95% CI, 1.5–6.5). Conclusions. Our study identified raising backyard poultry at home as a risk factor for illness with A(H7N9), suggesting the need for enhanced avian influenza surveillance in rural areas. PMID:27704029

Assessment of efficacy and safety of pandemic A/H1N1/2009 influenza vaccine in a group of health care workers.

PubMed

Mascagni, P; Vicenzi, Elisa; Kajaste-Rudnitski, Anna; Pellicciotta, G; Monti, A; Cervi, Carla; Vitalucci, Roberta; Toffoletto, F

2012-01-01

The development in an extremely short time of an efficacious and safe vaccine against the pandemi A/H1N1 virus was a challenge that involved the entire scientific community. To assess the immunological and clinical efficacy of the new H1N1v monovalent influenza vaccine (Focetria Novartis Vaccines, Siena, Italy) in a group of health care workers (HCWs). A total of 148 volunteer HCWs were enrolled between Mid-Novembre 2009 and December 2009. After measuring antibody titers, a single intramuscular dose of 7.5 microg of Focetria monovalent vaccine against A/H1N1/2009 influenza virus with MF59C.1 adjuvant was administered. Antibody titers (median value) before and after a single dose of vaccine, measured by means of standard beam-agglutination inhibition test (HAI), increased from 32 to 256 (p < 0.001). After vaccination, 79.7% of the subjects showed antibody seroconversion, and in 97.3% seroprotection was achieved. The ratio between the geometric means of antibody titers (GMTR) was 6.69. For the 3 subjects who reported symptoms of ILI (Influenza-like illness), a regular nasal-pharyngeal swab sample was taken to identify the virus type by RT-PCR, the laboratory results of tests performed on these samples were negative for pandemic A/H1N1/2009 virus. During the entire follow-up period of 6 months no severe adverse events occurred. The vaccine against pandemic A/H1N1/2009 virus provided protection against the virus and not only contributed to a significant immunization (according to EMEA criteria), but kept all 148 subjects under study free from A/H1N1/2009 influenza illness.

Progressive antigenic drift and phylogeny of human influenza A(H3N2) virus over five consecutive seasons (2009-2013) in Hangzhou, China.

PubMed

Shao, Tie-Juan; Li, Jun; Yu, Xin-Fen; Kou, Yu; Zhou, Yin-Yan; Qian, Xin

2014-12-01

Vaccine efficacy (VE) can be affected by progressive antigenic drift or any new reassortment of influenza viruses. To effectively track the evolution of human influenza A(H3N2) virus circulating in Hangzhou, China, a total of 65 clinical specimens were selected randomly from outpatients infected by A(H3N2) viruses during the study period from November 2009 to December 2013. The results of reduced VE and antigenic drift of the correspondent epitopes (C-D-E to A-B) suggest that the current vaccine provides suboptimal protection against the A(H3N2) strains circulating recently. Phylogenetic analysis of the entire HA and NA sequences demonstrated that these two genes underwent independent evolutionary pathways during recent seasons. The H3-based phylogenetic tree showed that a special strain A/Hangzhou/A289/2012 fell in a cluster among viruses with reduced VE predominantly circulating in 2013. Our findings underscore a possible early warning for the circulation of A(H3N2) variants with antigenic drift during the previous seasons. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

PubMed

Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

2014-03-01

We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.

Triclosan activates aryl hydrocarbon receptor (AhR)-dependent apoptosis and affects Cyp1a1 and Cyp1b1 expression in mouse neocortical neurons.

PubMed

Szychowski, Konrad A; Wnuk, Agnieszka; Kajta, Małgorzata; Wójtowicz, Anna K

2016-11-01

Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitizing products, such as soaps, toothpastes, and hair products. A number of studies have revealed the presence of TCS in human tissues, such as fat, liver and brain, in addition to blood and breast milk. The aim of the present study was to investigate the impact of TCS on AhR and Cyp1a1/Cyp1b1 signaling in mouse neocortical neurons in primary cultures. In addition to the use of selective ligands and siRNAs, expression levels of mRNA and proteins as well as caspase-3 activity, reactive oxygen species (ROS) formation, and lactate dehydrogenase (LDH) release have been measured. We also studied the involvement of the AhR in TCS-induced LDH release and caspase-3 activation as well as the effect of TCS on ROS generation. Cultures of neocortical neurons were prepared from Swiss mouse embryos on day 15/16 of gestation. The cells were cultured in phenol red-free Neurobasal medium with B27 and glutamine, and the neurons were exposed to 1 and 10µM TCS. Our experiments showed that the expression of AhR and Cyp1a1 mRNA decreased in cells exposed to 10µM TCS for 3 or 6h. In the case of Cyp1b1, mRNA expression remained unchanged compared with the control group following 3h of exposure to TCS, but after 6h, the mRNA expression of Cyp1b1 was decreased. Our results confirmed that the AhR is involved in the TCS mechanism of action, and our data demonstrated that after the cells were transfected with AhR siRNA, the cytotoxic and pro-apoptotic properties of TCS were decreased. The decrease in Cyp1a1 mRNA and protein expression levels accompanied by a decrease in its activity. The stimulation of Cyp1a1 activity produced by the application of an AhR agonist (βNF) was attenuated by TCS, whereas the addition of AhR antagonist (αNF) reversed the inhibitory effects of TCS. In our experiments, TCS diminished Cyp1b1 mRNA and enhanced its protein expression. In case of Cyp1a1 we observed

Complete Genome Sequence of Sulfuriferula sp. Strain AH1, a Sulfur-Oxidizing Autotroph Isolated from Weathered Mine Tailings from the Duluth Complex in Minnesota

PubMed Central

Roepke, Elizabeth W.; Hua, An An; Flood, Beverly E.; Bailey, Jake V.

2017-01-01

ABSTRACT We report the closed and annotated genome sequence of Sulfuriferula sp. strain AH1. Strain AH1 has a 2,877,007-bp chromosome that includes a partial Sox system for inorganic sulfur oxidation and a complete nitrogen fixation pathway. It also has a single 39,138-bp plasmid with genes for arsenic and mercury resistance. PMID:28798167

Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests.

PubMed

Balish, Amanda; Garten, Rebecca; Klimov, Alexander; Villanueva, Julie

2013-07-01

The performance of rapid influenza diagnostic tests (RIDTs) that detect influenza viral nucleoprotein (NP) antigen has been reported to be variable. Recent human infections with variant influenza A viruses that are circulating in pigs prompted the investigation of the analytical reactivity of RIDTs with these variant viruses. To determine analytical reactivity of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with the reactivity with recently circulating seasonal influenza A viruses. Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A viruses were prepared and tested in duplicate with seven RIDTs. All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs. Clinicians should be aware of the limitations of RIDTs to detect influenza A variant viruses. Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. Published 2012. This article is a US Government work and is in the public domain in the USA.

Human infection of novel avian influenza A(H7N4) virus.

PubMed

Tong, Xue-Cheng; Weng, Shan-Shan; Xue, Feng; Wu, Xing; Xu, Tian-Min; Zhang, Wen-Hong

2018-06-10

Multiple reassortant strains of novel, highly pathogenic avian influenza A have recently emerged and spread over the world. Here we report on a 68-year-old woman in Jiangsu, China, with influenza A(H7N4) infection and associated illness, which strongly demonstrating the ability of the virus to spread from animals to humans and thus emphasizing the importance of continuous surveillance of the emerging viruses. Copyright © 2018. Published by Elsevier Ltd.

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

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

Jaguin, Marie; Fardel, Olivier; Pôle Biologie, Centre Hospitalier Universitaire

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 significantlymore » 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.« less

Protective effect of A/H1N1 vaccination in immune-mediated disease--a prospectively controlled vaccination study.

PubMed

Adler, Sabine; Krivine, Anne; Weix, Janine; Rozenberg, Flore; Launay, Odile; Huesler, Juerg; Guillevin, Loïc; Villiger, Peter M

2012-04-01

To assess the 2009 influenza vaccine A/H1N1 on antibody response, side effects and disease activity in patients with immune-mediated diseases. Patients with RA, SpA, vasculitis (VAS) or CTD (n = 149) and healthy individuals (n = 40) received a single dose of adjuvanted A/H1N1 influenza vaccine. Sera were obtained before vaccination, and 3 weeks, 6 weeks and 6 months thereafter. A/H1N1 antibody titres were measured by haemagglutination inhibition (HAI) assay. Seroprotection was defined as specific antibody titre ≥ 1 : 40, seroconversion as 4-fold increase in antibody titre. Titres increased significantly in patients and controls with a maximum at Week 3, declining to levels below protection at Month 6 (P < 0.001). Seroprotection was more frequently reached in SpA and CTD than in RA and VAS (80 and 82% and 57 and 47%, respectively). There was a significantly negative impact by MTX (P < 0.001), rituximab (P = 0.0031) and abatacept (P = 0.045). Other DMARDs, glucocorticoids and TNF blockers did not significantly suppress response (P = 0.06, 0.11 and 0.81, respectively). A linear decline in response was noted in patients with increasing age (P < 0.001). Disease reactivation possibly related to vaccination was suspected in 8/149 patients. No prolonged side effects or A/H1N1 infections were noted. The results show that vaccination response is a function of disease type, intensity and character of medication and age. A single injection of adjuvanted influenza vaccine is sufficient to protect a high percentage of patients. Therefore, differential vaccination recommendations might in the future reduce costs and increase vaccination acceptance.

Detection and isolation of 2009 pandemic influenza A/H1N1 virus in commercial piggery, Lagos Nigeria.

PubMed

Meseko, C A; Odaibo, G N; Olaleye, D O

2014-01-10

WHO declared pandemic of A/H1N1 influenza in 2009 following global spread of the newly emerged strain of the virus from swine. Presently there is a dearth of data on the ecology of pandemic influenza H1N1 required for planning of intervention measures in sub Saharan Africa. Herein we report isolation of 2009 pandemic influenza A/H1N1 in an intensive mega piggery farms operation in South West Nigeria. Sentinel surveillance was carried out in a cohort of intensively reared pigs over a period of two years. Nasal swab specimens were collected at monthly interval from observed clinical cases of influenza like illness in pigs and pig handlers. Samples were analyzed by real time RT-PCR and isolation in chicken embryonated eggs. A total of 227 clinical cases of influenza like illness were observed among pigs out of which 31 (13.7%) were positive for influenza A matrix gene by real time RT-PCR. Virus isolation yielded 29 (12%) isolates out of which 18 (18%) were identified as influenza A/H1N1 by Heamaglutination Inhibition test using H1 antisera. RT-PCR positive samples were subtyped as 2009 pandemic A/H1N1 with subtype specific primers and probes. This is the first report of detection and isolation of pandemic influenza H1N1 from pigs in Nigeria. Continuous circulation of this virus in pigs may cause reassortments with seasonal influenza or mutations and substitutions in the gene that may result in the emergence of novel or pandemic influenza virus of economic and public health importance. Nigeria is considered a geographical hotspot of zoonotic diseases, which necessitate active surveillance and monitoring of emerging pandemic threats. Copyright © 2013 Elsevier B.V. All rights reserved.

Liver Biochemistry During the Course of Influenza A/H1N1 Infection.

PubMed

Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

2013-06-01

Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words "H1N1", "influenza A" and "liver". We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.

Liver Biochemistry During the Course of Influenza A/H1N1 Infection

PubMed Central

Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

2013-01-01

Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus. PMID:27785237

Metapopulation Dynamics Enable Persistence of Influenza A, Including A/H5N1, in Poultry

PubMed Central

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. PMID:24312455

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

PubMed Central

Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

2015-01-01

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

Environmental contamination and risk factors for transmission of highly pathogenic avian influenza A(H5N1) to humans, Cambodia, 2006-2010.

PubMed

Ly, Sowath; Vong, Sirenda; Cavailler, Philippe; Mumford, Elizabeth; Mey, Channa; Rith, Sareth; Van Kerkhove, Maria D; Sorn, San; Sok, Touch; Tarantola, Arnaud; Buchy, Philippe

2016-11-04

Highly pathogenic avian influenza A (H5N1) virus has been of public health concern since 2003. Probable risk factors for A(H5N1) transmission to human have been demonstrated in several studies or epidemiological reports. However, transmission patterns may differ according to demographic characteristics of the population and local practices. This article aggregates these data from three studies with data collected in the previous surveys in 2006 and 2007 to further examine the risks factors associated with presence of anti-A(H5) antibodies among villagers residing within outbreak areas. We aggregated 5-year data (2006-2010) from serology survey and matched case-control studies in Cambodia to further examine the risks factors associated with A(H5N1) infection among villagers in the outbreak areas. Serotesting among villagers detected 35 (1.5 % [0-2.6]) positive cases suggesting recent exposure to A(H5N1) virus. Practices associated with A(H5N1) infection among all ages were: having poultry cage or nesting area under or adjacent to the house (OR: 6.7 [1.6-28.3]; p = 0.010) and transporting poultry to market (OR: 17.6 [1.6-193.7]; p = 0.019). Practices found as risk factors for the infection among age under 20 years were swimming/bathing in ponds also accessed by domestic poultry (OR: 4.6 [1.1-19.1]; p = 0.038). Association with consuming wild birds reached borderline significance (p = 0.066). Our results suggest that swimming/bathing in contaminated pond water and close contact with poultry may present a risk of A(H5N1) transmission to human.

Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

PubMed Central

Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

2016-01-01

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

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

PubMed

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

2013-12-01

Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1. Copyright © 2013 Elsevier Ltd. All rights reserved.

Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season

PubMed Central

Santos, Katia Corrêa de Oliveira; da Silva, Daniela Bernardes Borges; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; de Paiva, Terezinha Maria

2017-01-01

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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 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(H1N1)pdm09 component of the vaccine for the 2016 influenza season. PMID:28380120

Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

PubMed

Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

2014-12-01

This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

On the intramolecular origin of the blue shift of A-H stretching frequencies: triatomic hydrides HAX.

PubMed

Karpfen, Alfred; Kryachko, Eugene S

2009-04-30

A series of intermolecular complexes formed between the triatomic hydrides HAX and various interaction partners are investigated computationally aiming (1) to demonstrate that either an appearance or nonappearance of a blue shift of the A-H stretching frequency is directly related to the sign of the intramolecular coupling that exists between the two degrees of freedom, the A-H and A-X bond lengths, and (2) to offer the following conjecture: the theoretical protonation of a triatomic neutral molecule HAX at the site X is a simple and rather efficient probe of a red or blue shift that the stretching frequency nu(A-H) undergoes upon complex formation regardless of whether this bond is directly involved in hydrogen bonding or not. In other words, to predict whether this A-H bond is capable to display a blue or red shift of nu(A-H), it suffices to compare the equilibrium structures and vibrational spectra of a given molecule with its protonated counterpart. The two above goals are achieved invoking a series of 11 triatomic molecules: HNO, HSN, HPO, and HPS characterized by a negative intramolecular coupling; HON and HNS as intermediate cases; and HOF, HOCl, HCN, HNC, and HCP with a positive intramolecular coupling. For these purposes, the latter molecules are investigated at the MP2/6-311++G(2p,2d) level in the neutral and protonated HAXH(+) forms as well as their complexes with H(2)O and with the fluoromethanes H(3)CF, H(2)CF(2), and HCF(3).

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

PubMed Central

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

2015-01-01

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

Screening a mouse liver gene expression Compendium Identifies Effectors of the Aryl Hydrocarbon receptor (AhR)

EPA Science Inventory

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological and toxic effects of 2,3, 7 ,8-tetrachlorodibenzo-p-dioxin {TCDD), dioxin-like compounds (DLC) as well as some drugs and endogenous tryptophan metabolites. Short-term act...

Multiple Introductions of Influenza A(H5N8) Virus into Poultry, Egypt, 2017.

PubMed

Salaheldin, Ahmed H; El-Hamid, Abd; Elbestawy, Ahmed R; Veits, Jutta; Hafez, Hafez M; Mettenleiter, Thomas C; Abdelwhab, Elsayed M

2018-05-01

After high mortality rates among commercial poultry were reported in Egypt in 2017, we genetically characterized 4 distinct influenza A(H5N8) viruses isolated from poultry. Full-genome analysis indicated separate introductions of H5N8 clade 2.3.4.4 reassortants from Europe and Asia into Egypt, which poses a serious threat for poultry and humans.

Relation among cytochrome P450, AH-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

USGS Publications Warehouse

Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

1994-01-01

Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P-450-associated monooxygenases and cytochrome P-450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r-2 often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the Ah receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

PubMed Central

Liang, Tan; Chen, Qianwei; Li, Qiang; Li, Rongwei; Tang, Jun; Hu, Rong; Zhong, Jun; Ge, Hongfei; Liu, Xin; Hua, Feng

2017-01-01

Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia. PMID:29088731

Neuroinvasive influenza virus A(H5N8) in fattening ducks, Hungary, 2015.

PubMed

Bányai, Krisztián; Bistyák, Andrea Tóthné; Thuma, Ákos; Gyuris, Éva; Ursu, Krisztina; Marton, Szilvia; Farkas, Szilvia L; Hortobágyi, Eleonóra; Bacsadi, Árpád; Dán, Ádám

2016-09-01

Highly pathogenic avian influenza (HPAI) A virus H5N8 was detected in far east Asian countries during 2014 and emerged in late 2014 in European countries. Hungary reported a HPAI A(H5N8) outbreak during late winter of 2015 at a Pekin duck fattening facility. Epidemiologic monitoring was extended to holdings in neighboring areas and nearby habitats used by wild birds but failed to identify the source of infection. In addition to respiratory symptoms, the affected birds showed lethargy and neuronal signs, including torticollis. Consistent with this finding, influenza A virus antigen was detected in large quantity in the brain. Molecular analysis of the identified strain showed very close genetic relationship (and >99% nucleotide sequence identity) with co-circulating HPAI A(H5N8) strains. A number of unique or rarely detected amino acid changes was detected in the HA (T220I, R512G), the M2 (I39M), the NA (T211I), the NS1 (P85T), and the PB2 (I261V) proteins of the Hungarian strain. Further studies are needed to demonstrate whether any of these mutations can be linked to neuroinvasiveness and neurovirulence in ducks. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative liver accumulation of dioxin-like compounds in sheep and cattle: Possible role of AhR-mediated xenobiotic metabolizing enzymes.

PubMed

Girolami, F; Spalenza, V; Benedetto, A; Manzini, L; Badino, P; Abete, M C; Nebbia, C

2016-11-15

PCDDs, PCDFs, and PCBs are persistent organic pollutants (POPs) that accumulate in animal products and may pose serious health problems. Those able to bind the aryl hydrocarbon receptor (AhR), eliciting a plethora of toxic responses, are defined dioxin-like (DL) compounds, while the remainders are called non-DL (NDL). An EFSA opinion has highlighted the tendency of ovine liver to specifically accumulate DL-compounds to a greater extent than any other farmed ruminant species. To examine the possible role in such an accumulation of xenobiotic metabolizing enzymes (XME) involved in DL-compound biotransformation, liver samples were collected from ewes and cows reared in an area known for low dioxin contamination. A related paper reported that sheep livers had about 5-fold higher DL-compound concentrations than cattle livers, while the content of the six marker NDL-PCBs did not differ between species. Specimens from the same animals were subjected to gene expression analysis for AhR, AhR nuclear translocator (ARNT) and AhR-dependent oxidative and conjugative pathways; XME protein expression and activities were also investigated. Both AhR and ARNT mRNA levels were about 2-fold lower in ovine samples and the same occurred for CYP1A1 and CYP1A2, being approximately 3- and 9-fold less expressed in sheep compared to cattle, while CYP1B1 could be detectable in cattle only. The results of the immunoblotting and catalytic activity (most notably EROD) measurements of the CYP1A family enzymes were in line with the gene expression data. By contrast, phase II enzyme expression and activities in sheep were higher (UGT1A) or similar (GSTA1, NQO1) to those recorded in cattle. The overall low expression of CYP1 family enzymes in the sheep is in line with the observed liver accumulation of DL-compounds and is expected to affect the kinetics and the dynamics of other POPs such as many polycyclic aromatic hydrocarbons, as well as of toxins (e.g. aflatoxins) or drugs (e.g. benzimidazole

Norisoboldine, a natural AhR agonist, promotes Treg differentiation and attenuates colitis via targeting glycolysis and subsequent NAD+/SIRT1/SUV39H1/H3K9me3 signaling pathway.

PubMed

Lv, Qi; Wang, Kai; Qiao, Simiao; Yang, Ling; Xin, Yirong; Dai, Yue; Wei, Zhifeng

2018-02-15

Norisoboldine (NOR), a natural aryl hydrocarbon receptor (AhR) agonist, has been demonstrated to attenuate ulcerative colitis (UC) and induce the generation of Treg cells. Under UC condition, hypoxia widely exists in colonic mucosa, and secondary changes of microRNAs (miRs) expressions and glycolysis contribute to Treg differentiation. At present, we worked for exploring the deep mechanisms for NOR-promoted Treg differentiation in hypoxia and its subsequent anti-UC action from the angle of AhR/miR or AhR/glycolysis axis. Results showed that NOR promoted Treg differentiation in hypoxia and the effect was stronger relative to normoxia. It activated AhR in CD4 + T cells under hypoxic microenvironment; CH223191 (a specific AhR antagonist) and siAhR-3 abolished NOR-promoted Treg differentiation. Furthermore, the progress of glycolysis, levels of Glut1 and HK2, and expression of miR-31 rather than miR-219 and miR-490 in CD4 + T cells were downregulated by NOR treatment under hypoxic microenvironment. However, HK2 plasmid but not miR-31 mimic significantly interfered NOR-enhanced Treg polarization. In addition, NOR reduced NAD + and SIRT1 levels, facilitated the ubiquitin-proteasomal degradation of SUV39H1 protein, and inhibited the enrichment of H3K9me3 at -1, 201 to -1,500 region of Foxp3 promoter in CD4 + T cells under hypoxic microenvironment, which was weakened by HK2 plasmid, CH223191, and siAhR-3. Finally, the correlation between NOR-mediated activation of AhR, repression of glycolysis, regulation of NAD + /SIRT1/SUV39H1/H3K9me3 signals, induction of Treg cells, and remission of colitis was confirmed in mice with DSS-induced colitis by using CH223191 and HK2 plasmid. In conclusion, NOR promoted Treg differentiation and then alleviated the development of colitis by regulating AhR/glycolysis axis and subsequent NAD + /SIRT1/SUV39H1/H3K9me3 signaling pathway.

Bt proteins Cry1Ah and Cry2Ab do not affect cotton aphid Aphis gossypii and ladybeetle Propylea japonica

PubMed Central

Zhao, Yao; Zhang, Shuai; Luo, Jun-Yu; Wang, Chun-Yi; Lv, Li-Min; Wang, Xiao-Ping; Cui, Jin-Jie; Lei, Chao-Liang

2016-01-01

Plant varieties expressing the Bt (Bacillus thuringiensis) insecticidal proteins Cry1Ah and Cry2Ab have potential commercialization prospects in China. However, their potential effects on non-target arthropods (NTAs) remain uncharacterized. The cotton aphid Aphis gossypii is a worldwide pest that damages various important crops. The ladybeetle Propylea japonica is a common and abundant natural enemy in many cropping systems in East Asia. In the present study, the effects of Cry1Ah and Cry2Ab proteins on A. gossypii and P. japonica were assessed from three aspects. First, neither of the Cry proteins affected the growth or developmental characteristics of the two test insects. Second, the expression levels of the detoxification-related genes of the two test insects did not change significantly in either Cry protein treatment. Third, neither of the Cry proteins had a favourable effect on the expression of genes associated with the amino acid metabolism of A. gossypii and the nutrition utilization of P. japonica. In conclusion, the Cry1Ah and Cry2Ab proteins do not appear to affect the cotton aphid A. gossypii or the ladybeetle P. japonica. PMID:26829252

Assessment of EchoMRI-AH versus dual-energy X-ray absorptiometry by iDXA to measure human body composition.

PubMed

Marlatt, K L; Greenway, F L; Ravussin, E

2017-04-01

Comparison of percent fat mass across different body composition analysis devices is important given variation in technology accuracy and precision, as well as the growing need for cross-validation of devices often applied across longitudinal studies. We compared EchoMRI-AH and Lunar iDXA quantification of percent body fat (PBF) in 84 adults (43M, 41F), with the mean age 39.7±15.9 years and body mass index (BMI) 26.2±5.3 kg/m 2 . PBF correlated strongly between devices (r>0.95, P<0.0001). A prediction equation was derived in half of the subjects, and the other half were used to cross-validate the proposed equation (EchoMRI-AH PBF=[(0.94 × iDXA PBF)+(0.14 × Age)+(3.3 × Female)-8.83). The mean PBF difference (predicted-measured) in the validation group was not different from 0 (diff=0.27%, 95% confidence interval: -0.42-0.96, P=0.430). Bland-Altman plots showed a bias with higher measured PBF on EchoMRI-AH versus iDXA in all 84 subjects (β=0.13, P<0.0001). The proposed prediction equation was valid in our cross-validation sample, and it has the potential to be applied across multicenter studies.

The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family.

PubMed

Ulasli, Mustafa; Gurses, Serdar A; Bayraktar, Recep; Yumrutas, Onder; Oztuzcu, Serdar; Igci, Mehri; Igci, Yusuf Ziya; Cakmak, Ecir Ali; Arslan, Ahmet

2014-03-01

Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus-A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2(-∆∆Ct) method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID50/ml (tissue culture infectious dose that will produce cytopathic effect in 50% of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8 hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s).

[Clinical characteristics and therapeutic experience of case of severe highly pathogenic A/H5N1 avian influenza with bronchopleural fistula].

PubMed

Zhang, Hua-ping; Zeng, Yi-ming; Lin, Zhang-shu; Chen, Wei; Liang, Jian-sheng; Zhang, Hong; Huang, Wen-rui

2009-05-01

To summarize the clinical characteristics and therapeutic experience of A/H5N1 infected patient with intractable bronchopleural fistula. The data of a patient with A/H5N1 infection complicated with bronchopleural fistula was collected and analyzed. A 44-year-old woman with pneuminian was diagnosed as A/H5N1 infection by reverse-transcription polymerase chain reaction (RT-PCR) in laboratory from the sample of secretion of respiratory tracts. She had exposed to sick or dead poultry 3 days before development of illness. She developed acute respiratory distress syndrome 7 days after onset of sickness. After comprehensive management with antiviral agents, antibiotics, convalescent serum and invasive ventilation, her clinical condition improved and turned to stable. However, 16 days after onset of illness, her clinical situation deteriorated due to ventilator-associated pneumonia, bilateral pneumothorax and persistent right bronchopleural fistula. After partly failure of beside assist thoracoscopy to fix the pleural fistula, transbronchoscopic bronchial occlusion by autoblood was explored and the air leakage stopped soon after occlusion. Three days after the autoblood clot was expectorated out and air leak recurred. Then, bronchopleural fistula on the surface of visceral pleura was successfully blocked by biogel and OB gel through pleural cavity by fibrobronchoscopy. The patient was discharged from the hospital 99 days after onset of illness (at the 94th hospital day). Bronchopleural fistula was an intractable complication for patient with A/H5N1 infection. Occlusion operation by biogel and OB gel through bronchoscopy might be an alternative choice for fixing the bronchopleural fistula.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

PubMed Central

Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

2016-01-01

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

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.

PubMed

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.

Detection of an Avian Lineage Influenza A(H7N2) Virus in Air and Surface Samples at a New York City Feline Quarantine Facility.

PubMed

Blachere, Francoise M; Lindsley, William G; Weber, Angela M; Beezhold, Donald H; Thewlis, Robert E; Mead, Kenneth R; Noti, John D

2018-05-16

In December 2016, an outbreak of low pathogenicity avian influenza (LPAI) A(H7N2) occurred in cats at a New York City animal shelter and quickly spread to other shelters in New York and Pennsylvania. The A(H7N2) virus also spread to an attending veterinarian. In response, 500 cats were transferred from these shelters to a temporary quarantine facility for continued monitoring and treatment. The objectives of this study was to assess the occupational risk of A(H7N2) exposure among emergency response workers at the feline quarantine facility. Aerosol and surface samples were collected from inside and outside the isolation zones of the quarantine facility. Samples were screened for A(H7N2) by quantitative RT-PCR and analyzed in embryonated chicken eggs for infectious virus. H7N2 virus was detected by RT-PCR in 28 of 29 aerosol samples collected in the high-risk isolation (hot) zone with 70.9% on particles with aerodynamic diameters >4 μm, 27.7% in 1-4 μm, and 1.4% in <1 μm. Seventeen of 22 surface samples from the high-risk isolation zone were also H7N2-positive with an average M1 copy number of 1.3 x 10 3 . Passage of aerosol and surface samples in eggs confirmed that infectious virus was present throughout the high-risk zones in the quarantine facility. By measuring particle size, distribution, and infectivity, our study suggests that the A(H7N2) virus had the potential to spread by airborne transmission and/or direct contact with viral-laden fomites. These results warranted continued A(H7N2) surveillance and transmission-based precautions during the treatment and care of infected cats. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Influenza A(H1N1)pdm09 Virus among Healthy Show Pigs, United States

PubMed Central

Bender, Jeffrey B.; Bridges, Carolyn B.; Daly, Russell F.; Krueger, Whitney S.; Male, Michael J.; Heil, Gary L.; Friary, John A.; Derby, Robin B.; Cox, Nancy J.

2012-01-01

Within 5 months after the earliest detection of human influenza A(H1N1)pdm09 virus, we found molecular and culture evidence of the virus in healthy US show pigs. The mixing of humans and pigs at swine shows possibly could further the geographic and cross-species spread of influenza A viruses. PMID:22932697

Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1.

PubMed

Torun, Sebahat D; Torun, Fuat; Catak, Binali

2010-10-10

Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination is necessary. Efforts for orienting

Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1

PubMed Central

2010-01-01

Background Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. Methods A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. Results A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Conclusions Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination

Interim estimates of divergence date and vaccine strain match of human influenza A(H3N2) virus from systematic influenza surveillance (2010-2015) in Hangzhou, southeast of China.

PubMed

Li, Jun; Zhou, Yin-yan; Kou, Yu; Yu, Xin-fen; Zheng, Zhi-bei; Yang, Xu-hui; Wang, Hao-qiu

2015-11-01

In the post-pandemic period 2010-2015, seasonal influenza A(H3N2) virus predominated in Hangzhou, southeast of China, with an increased activity and semi-annual seasons. This study utilized HA virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza A(H3N2) virus from systematic influenza surveillance in Hangzhou. Virological and serological analyses of 124 representative A(H3N2) viruses from prospective studies of systematic surveillance samples were conducted to quantify the genetic and antigenic characteristics and their vaccine strain match. Bayesian phylogenetic inference showed that two separate subgroups 3C.3 and 3C.2 probably diverged from group 3C in early 2012 and then evolved into groups 3C.3a and 3C.2a, respectively, in the 2014/15 influenza season. Furthermore, high amino acid substitution rates of the HA1 subunit were found in A(H3N2) group 3C.2a variants, indicating that increased antigenic drift of A(H3N2) group 3C.2a virus is associated with a vaccine mismatch to the 2015/16 vaccine reference strain Switzerland/9715293/2013 (group 3C.3a). A portion of the group 3C.2a isolates are not covered by the current A(H3N2) vaccine strain. These findings offer insights into the emergence of group 3C.2a variants with epidemic potential in the imminent influenza seasons. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mathematical modeling of a radio-frequency path for IEEE 802.11ah based wireless sensor networks

NASA Astrophysics Data System (ADS)

Tyshchenko, Igor; Cherepanov, Alexander; Dmitrii, Vakhnin; Popova, Mariia

2017-09-01

This article discusses the process of creating the mathematical model of a radio-frequency path for an IEEE 802.11ah based wireless sensor networks using M atLab Simulink CAD tools. In addition, it describes occurring perturbing effects and determining the presence of a useful signal in the received mixture.

Bond strength to root dentin and fluid filtration test of AH Plus/gutta-percha, EndoREZ and RealSeal systems

PubMed Central

MAHDI, Alaa Abdul; BOLAÑOS-CARMONA, Victoria; GONZALEZ-LOPEZ, Santiago

2013-01-01

Objectives To investigate the bond strength and seal ability produced by AH Plus/gutta-percha, EndoREZ and RealSeal systems to root canal dentin. Material and Methods Sixty extracted single-root human teeth, instrumented manually to size 40, were divided into three groups (n=20) according to the sealer used; G1: AH Plus, G2: EndoREZ, and G3: RealSeal sealers. After filling using the lateral condensation technique, each sealer group was randomly divided into two subgroups according to the tests applied (n=10 for µPush-out test and n=10 for fluid filtration test). A fluid filtration method was used for quantitative evaluation of apical leakage. Four 1-mm-thick slices (cervical and medium level) were obtained from each root sample and a µPush-out test was performed. Failure modes were examined under microscopy at 40x, and a one-way ANOVA was applied to analyze the permeability. Non-parametrical statistics for related (Friedman's and Wilcoxon's rank tests) or unrelated samples (Kruskal-Wallis' and Mann-Whitney's tests) allowed for comparisons of µPush-out strength values among materials at the different levels. Statistical significance was accepted for p values <.05. Results There are no significant differences among fluid filtration of the three sealers. The sealer/core material does not significantly influence the µPush-out bond strength values (F=2.49; p=0.10), although statistically significant differences were detected with regard to root level (Chi2=23.93; p<0.001). AH Plus and RealSeal obtained higher bond strength to intraradicular dentin in the medium root slices. Conclusions There are no significant differences between the permeability and global µPush-out bond strength to root canal dentin achieved by AH Plus/gutta-percha, EndoREZ and RealSeal systems. PMID:24037078

Clinical features, complications and mortality in critically ill patients with 2009 influenza A(H1N1) in Sfax,Tunisia.

PubMed

Damak, Hassen; Chtara, Kamilia; Bahloul, Mabrouk; Kallel, Hatem; Chaari, Anis; Ksibi, Hichem; Chaari, Adel; Chelly, Hedi; Rekik, Noureddine; Ben Hamida, Chokri; Bouaziz, Mounir

2011-07-01

Africa, as the rest of the world, was touched by the 2009 pandemic influenza A(H1N1). In the literature, a few publications covering this subject emerged from this continent. We prospectively describe baseline characteristics, treatment and outcomes of consecutive critically ill patients with confirmed 2009 influenza A(H1N1) in the intensive care unit (ICU) of Sfax hospital. From 29 November 2009 through 21 January 2010, 32 patients with confirmed 2009 influenza A(H1N1) were admitted to our ICU. We prospectively analysed data and outcomes of these patients and compared survivors and dead patients to identify any predictors of death. Patients were young (mean, 36·1 [SD], 20·7 years) and 21 (65·6%) of whom had co-morbidities. During ICU care, 29 (90·6%) patients had respiratory failure; among these, 15 (46·9%) patients required invasive ventilation with a median duration of 9 (IQR 3-12) days. In our experience, respiratory dysfunction can remain isolated but may also be associated with other dysfunctions or complications, such as, septic shock, seizures, myasthenia gravis exacerbation, Guillan-Barre syndrome, acute renal failure, nosocomial infections and biological disturbances. The nine patients (28·1%) who died had greater initial severity of illness (SAPS II and sequential organ failure assessment (SOFA) scores) but also a higher SOFA score and increasing severity of organ dysfunction during their ICU evolution. Critical illness from the 2009 influenza A(H1N1) in Sfax occurred in young individuals and was associated with severe acute respiratory and additional organ system failure. SAPS II and SOFA scores at ICU admission, and also during evolution, constitute a good predictor of death. © 2011 Blackwell Publishing Ltd.

Drug susceptibility of influenza A/H3N2 strains co-circulating during 2009 influenza pandemic: first report from Mumbai.

PubMed

Gohil, Devanshi J; Kothari, Sweta T; Shinde, Pramod S; Chintakrindi, Anand S; Meharunkar, Rhuta; Warke, Rajas V; Kanyalkar, Meena A; Chowdhary, Abhay S; Deshmukh, Ranjana A

2015-01-01

From its first instance in 1977, resistance to amantadine, a matrix (M2) inhibitor has been increasing among influenza A/H3N2, thus propelling the use of oseltamivir, a neuraminidase (NA) inhibitor as a next line drug. Information on drug susceptibility to amantadine and neuraminidase inhibitors for influenza A/H3N2 viruses in India is limited with no published data from Mumbai. This study aimed at examining the sensitivity to M2 and NA inhibitors of influenza A/H3N2 strains isolated from 2009 to 2011 in Mumbai. Nasopharyngeal swabs positive for influenza A/H3N2 virus were inoculated on Madin-Darby canine kidney (MDCK) cell line for virus isolation. Molecular analysis of NA and M2 genes was used to detect known mutations contributing to resistance. Resistance to neuraminidase was assayed using a commercially available chemiluminescence based NA-Star assay kit. Genotypically, all isolates were observed to harbor mutations known to confer resistance to amantadine. However, no know mutations conferring resistance to NA inhibitors were detected. The mean IC50 value for oseltamivir was 0.25 nM. One strain with reduced susceptibility to the neuraminidase inhibitor (IC₅₀=4.08 nM) was isolated from a patient who had received oseltamivir treatment. Phylogenetic analysis postulate the emergence of amantadine resistance in Mumbai may be due to genetic reassortment with the strains circulating in Asia and North America. Surveillance of drug susceptibility helped us to identify an isolate with reduced sensitivity to oseltamivir. Therefore, we infer that such surveillance would help in understanding possible trends underlying the emergence of resistant variants in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

Responses to A(H1N1)pdm09 Influenza Vaccines in Participants Previously Vaccinated With Seasonal Influenza Vaccine: A Randomized, Observer-Blind, Controlled Study

PubMed Central

Roy-Ghanta, Sumita; Van der Most, Robbert; Li, Ping; Vaughn, David W.

2014-01-01

Background. Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Methods. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4+/CD8+ T cells, memory B cells, and plasmablasts were assessed. Results. Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4+ T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4+ T cells, homologous memory B cells, and plasmablasts. Conclusions. In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed. Registration. Clinical Trials.gov identifier NCT00707967. PMID:24864125

Protective effects of levamisole, acetylsalicylic acid, and α-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model.

PubMed

Gostomska-Pampuch, Kinga; Ostrowska, Alicja; Kuropka, Piotr; Dobrzyński, Maciej; Ziółkowski, Piotr; Kowalczyk, Artur; Łukaszewicz, Ewa; Gamian, Andrzej; Całkosiński, Ireneusz

2017-04-01

Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

Mutations of novel influenza A(H10N8) virus in chicken eggs and MDCK cells.

PubMed

Yang, Jian; Zhang, Ting; Guo, Li; Hu, Yongfeng; Li, Jinlin; Su, Haoxiang; Xiao, Yan; Ren, Xianwen; Dong, Jie; Sun, Lilian; Xiao, Yan; Li, Li; Yang, Fan; Wang, Jianwei; Yuan, Hui; Jin, Qi

2014-09-01

The recent emergence of human infection with influenza A(H10N8) virus is an urgent public health concern. Genomic analysis showed that the virus was conserved in chicken eggs but presented substantial adaptive mutations in MDCK cells. Our results provide additional evidence for the avian origin of this influenza virus.

Characteristics of a Widespread Community Cluster of H275Y Oseltamivir-Resistant A(H1N1)pdm09 Influenza in Australia

PubMed Central

Hurt, A. C.; Hardie, K.; Wilson, N. J.; Deng, Y. M.; Osbourn, M.; Leang, S. K.; Lee, R. T. C.; Iannello, P.; Gehrig, N.; Shaw, R.; Wark, P.; Caldwell, N.; Givney, R. C.; Xue, L.; Maurer-Stroh, S.; Dwyer, D. E.; Wang, B.; Smith, D. W.; Levy, A.; Booy, R.; Dixit, R.; Merritt, T.; Kelso, A.; Dalton, C.; Durrheim, D.; Barr, I. G.

2012-01-01

Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely. PMID:22561367

Risk Factors for Influenza A(H1N1)pdm09 among Students, Beijing, China

PubMed Central

Zheng, Yang; Duan, Wei; Yang, Peng; Zhang, Yi; Wang, Xiaoli; Zhang, Li; Liyanage, Surabhi S.

2013-01-01

To identify risk factors associated with influenza A(H1N1)pdm09 among students in Beijing, China, we conducted a case–control study. Participants (304 case-patients and 608 controls, age range 6–19 years) were interviewed by using a standardized questionnaire. We found that in addition to vaccination, nonpharmaceutical interventions appeared to be protective. PMID:23347500

Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012.

PubMed

Lopez-Martinez, Irma; Balish, Amanda; Barrera-Badillo, Gisela; Jones, Joyce; Nuñez-García, Tatiana E; Jang, Yunho; Aparicio-Antonio, Rodrigo; Azziz-Baumgartner, Eduardo; Belser, Jessica A; Ramirez-Gonzalez, José E; Pedersen, Janice C; Ortiz-Alcantara, Joanna; Gonzalez-Duran, Elizabeth; Shu, Bo; Emery, Shannon L; Poh, Mee K; Reyes-Teran, Gustavo; Vazquez-Perez, Joel A; Avila-Rios, Santiago; Uyeki, Timothy; Lindstrom, Stephen; Villanueva, Julie; Tokars, Jerome; Ruiz-Matus, Cuitláhuac; Gonzalez-Roldan, Jesus F; Schmitt, Beverly; Klimov, Alexander; Cox, Nancy; Kuri-Morales, Pablo; Davis, C Todd; Diaz-Quiñonez, José Alberto

2013-01-01

We identified 2 poultry workers with conjunctivitis caused by highly pathogenic avian influenza A(H7N3) viruses in Jalisco, Mexico. Genomic and antigenic analyses of 1 isolate indicated relatedness to poultry and wild bird subtype H7N3 viruses from North America. This isolate had a multibasic cleavage site that might have been derived from recombination with host rRNA.

Screening for Influenza A(H1N1)pdm09, Auckland International Airport, New Zealand

PubMed Central

Hale, Michael J.; Baker, Michael G.

2012-01-01

Entry screening for influenza A(H1N1)pdm09 at Auckland International Airport, New Zealand, detected 4 cases, which were later confirmed, among 456,518 passengers arriving April 27–June 22, 2009. On the basis of national influenza surveillance data, which suggest that ≈69 infected travelers passed through the airport, sensitivity for screening was only 5.8%. PMID:22516105

Recruiting black Americans in a large cohort study: the Adventist Health Study-2 (AHS-2) design, methods and participant characteristics.

PubMed

Herring, R Patti; Butler, Terry; Hall, Sonja; Montgomery, Susanne B; Fraser, Gary E

2010-01-01

The goal of the prospective Adventist Health Study-2 (AHS-2) was to examine the relationship between diet and risk of breast, prostate and colon cancers in Black and White participants. This paper describes the study design, recruitment methods, response rates, and characteristics of Blacks in the AHS-2, thus providing insights about effective strategies to recruit Blacks to participate in research studies. We designed a church-based recruitment model and trained local recruiters who used various strategies to recruit participants in their churches. Participants completed a 50-page self-administered dietary and lifestyle questionnaire. Participants are Black Seventh-day Adventists, aged 30-109 years, and members of 1,209 Black churches throughout the United States and Canada. Approximately 48,328 Blacks from an estimated target group of over 90,000 signed up for the study and 25,087 completed the questionnaire, comprising about 26% of the larger 97,000 AHS-2-member cohort. Participants were diverse in age, geographic location, education, and income. Seventy percent were female with a median age of 59 years. In spite of many recruitment challenges and barriers, we successfully recruited a large cohort whose data should provide some answers as to why Blacks have poorer health outcomes than several other ethnic groups, and help explain existing health disparities.

Acute Respiratory Distress Syndrome Secondary to Influenza A(H1N1)pdm09: Clinical Characteristics and Mortality Predictors.

PubMed

Hernández-Cárdenas, Carmen Margarita; Serna-Secundino, Héctor; García-Olazarán, José Guadalupe; Aguilar-Pérez, Cristina Leticia; Rocha-Machado, Jesús; Campos-Calderón, Luis Fernando; Lugo-Goytia, Gustavo

2016-01-01

Acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09 virus is the leading cause of death among this patient population. Expanding the knowledge of its course and predictors of mortality is relevant to decision making. We aimed to describe the clinical characteristics and identify factors associated with mortality in patients with acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09 during the 2013-2014 influenza season. This is an observational study of a prospective cohort of 70 patients with acute respiratory distress syndrome and influenza A(H1N1) pdm09 seen in an academic medical center. Multivariate logistic regression was used to identify the independent mortality predictors. Bootstrap was used for internal model validation. This cohort was represented by young adults (43 ± 11 years old). Obesity was present in 62.5% and was not associated with mortality. Mortality at 28 days and at discharge from the respiratory intensive care unit was 14 and 20%, respectively. All patients met the criteria for acute respiratory distress syndrome, 73% had vasodilatory shock, and 27.1% had acute kidney injury on respiratory intensive care unit admission. We observed a high incidence of intensive care unit-acquired weakness (81.4%). Ventilator-associated pneumonia developed in 47.1% and was not associated with mortality. In multivariate analysis, independent risk factors for intensive care unit mortality were age (odds ratio [OR] = 1.102), white blood cell count (OR = 1.22), and lactate dehydrogenase levels (OR = 1.004) on admission to the intensive care unit. We described the clinical characteristics and course of a cohort of patients with acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09, and developed a predictive model of mortality based on the covariates age, levels of lactate dehydrogenase, and white cell count on admission to the respiratory intensive care unit.

The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection.

PubMed

Funaki, Takanori; Shoji, Kensuke; Yotani, Nobuyuki; Katsuta, Tomohiro; Miyazaki, Osamu; Nosaka, Shunsuke; Masaki, Hidekazu; Saitoh, Akihiko

2013-11-04

Most illnesses caused by pandemic influenza A (H1N1) pdm09 virus (A/H1N1) infection are acute and self-limiting among children. However, in some children, disease progression is rapid and may require hospitalization and transfer to a pediatric intensive care unit (PICU). We investigated factors associated with rapid disease progression among children admitted to hospital for A/H1N1 infection, particularly findings on initial chest radiographs. In this retrospective study, we investigated the records of children who had received a laboratory or clinical diagnosis of A/H1N1 infection and were admitted to the largest children's hospital in Japan between May 2009 and March 2010. The medical records were reviewed for age, underlying diseases, vital signs on admission, initial chest radiographic findings, and clinical outcomes. According to chest radiographic findings, patients were classified into 4 groups, as follows: [1] normal (n = 46), [2] hilar and/or peribronchial markings alone (n = 64), [3] consolidation (n = 64), and [4] other findings (n = 29). Factors associated with clinical outcomes were analyzed using logistic regression. Two hundreds and three patients (median 6.8 years) were enrolled in this study. Fifteen percent (31/203) of patients were admitted to PICU. Among 31 patients, 39% (12/31) of patients required mechanical ventilation (MV). When the initial chest radiographic findings were compared between patients with consolidation (n = 64) and those without consolidation (n = 139), a higher percentage of patients with consolidation were admitted to PICU (29.7% vs.8.6%, P < 0.001) and required MV (17.2% vs. 0.7%, P < 0.001). These findings remain significant when the data were analyzed with the logistic regression (P < 0.001, P < 0.001, respectively). Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection.

Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

An advanced 125 Ah individual pressure vessel (IPV) nickel-hydrogen cell was designed. The primary function of the advanced cell, is to store and deliver energy for long term, low earth-orbit (LEO) spacecraft missions. The new features of this design are: (1) use of 26 percent rather than 31 percent potassium hydroxide (KOH) electrolyte, (2) use of a patented catalyzed wall wick, (3) use of serrated edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management, and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion. Six 125 Ah flight cells based on this design were fabricated by Eagle-Picher. Three of the cells contain all of the advanced features (test cells) and three are the same as the test cells except they don't have catalyst on the wall wick (control cells). All six cells are in the process of being evaluated in a LEO cycle life test. The cells have accumulated about 4700 LEO cycles (60 percent DOD 10 C). There have been no cell failures, the catalyzed wall wick cells however, are performing better.

Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen battery cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1990-01-01

An advanced 125 Ah individual pressure vessel (IPV) nickel-hydrogen cell was designed. The primary function of the advanced cell is to store and deliver energy for long-term, low earth-orbit (LEO) spacecraft missions. The new features of this design are: (1) use of 26 percent rather than 31 percent potassium hydroxide (KOH) electrolyte, (2) use of a patented catalyzed wall wick, (3) use of serrated-edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management, and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion. Six 125-Ah flight cells based on this design were fabricated by Eagle-Picher. Three of the cells contain all of the advanced features (test cells) and three are the same as the test cells except they don't have catalyst on the wall wick (control cells). All six cells are in the process of being evaluated in a LEO cycle life test. The cells have accumulated about 4700 LEO cycles (60 percent DOD 10 C). There have been no cell failures; the catalyzed wall wick cells, however, are performing better.

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

PubMed Central

Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

2014-01-01

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

Evaluation of the potential effects of AS03-adjuvanted A(H1N1)pdm09 vaccine administration on the central nervous system of non-primed and A(H1N1)pdm09-primed cotton rats.

PubMed

Planty, Camille; Mallett, Corey P; Yim, Kevin; Blanco, Jorge C G; Boukhvalova, Marina; March, Thomas; van der Most, Robbert; Destexhe, Eric

2017-01-02

An increased risk of narcolepsy following administration of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine (Pandemrix™) was described in children and adolescents in certain European countries. We investigated the potential effects of administration of the AS03-adjuvanted vaccine, non-adjuvanted vaccine antigen and AS03 Adjuvant System alone, on the central nervous system (CNS) in one-month-old cotton rats. Naïve or A(H1N1)pdm09 virus-primed animals received 2 or 3 intramuscular injections, respectively, of test article or saline at 2-week intervals. Parameters related to systemic inflammation (hematology, serum IL-6/IFN-γ/TNF-α) were assessed. Potential effects on the CNS were investigated by histopathological evaluation of brain sections stained with hematoxylin-and-eosin, or by immunohistochemical staining of microglia, using Iba1 and CD68 as markers for microglia identification/activation, albumin as indicator of vascular leakage, and hypocretin. We also determined cerebrospinal fluid (CSF) hypocretin levels and hemagglutination-inhibiting antibody titers. Immunogenicity of the AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine was confirmed by the induction of hemagglutination-inhibiting antibodies. Both AS03-adjuvanted vaccine and AS03 alone activated transient innate (neutrophils/eosinophils) immune responses. No serum cytokines were detected. CNS analyses revealed neither microglia activation nor inflammatory cellular infiltrates in the brain. No differences between treatment groups were detected for albumin extravascular leakage, CSF hypocretin levels, numbers of hypocretin-positive neuronal bodies or distributions of hypocretin-positive axonal/dendritic projections. Consequently, there was no evidence that intramuscular administration of the test articles promoted inflammation or damage in the CNS, or blood-brain barrier disruption, in this model.

Evaluation of the potential effects of AS03-adjuvanted A(H1N1)pdm09 vaccine administration on the central nervous system of non-primed and A(H1N1)pdm09-primed cotton rats

PubMed Central

Planty, Camille; Mallett, Corey P.; Yim, Kevin; Blanco, Jorge C. G.; Boukhvalova, Marina; March, Thomas; van der Most, Robbert; Destexhe, Eric

2017-01-01

ABSTRACT An increased risk of narcolepsy following administration of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine (Pandemrix™) was described in children and adolescents in certain European countries. We investigated the potential effects of administration of the AS03-adjuvanted vaccine, non-adjuvanted vaccine antigen and AS03 Adjuvant System alone, on the central nervous system (CNS) in one-month-old cotton rats. Naïve or A(H1N1)pdm09 virus-primed animals received 2 or 3 intramuscular injections, respectively, of test article or saline at 2-week intervals. Parameters related to systemic inflammation (hematology, serum IL-6/IFN-γ/TNF-α) were assessed. Potential effects on the CNS were investigated by histopathological evaluation of brain sections stained with hematoxylin-and-eosin, or by immunohistochemical staining of microglia, using Iba1 and CD68 as markers for microglia identification/activation, albumin as indicator of vascular leakage, and hypocretin. We also determined cerebrospinal fluid (CSF) hypocretin levels and hemagglutination-inhibiting antibody titers. Immunogenicity of the AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine was confirmed by the induction of hemagglutination-inhibiting antibodies. Both AS03-adjuvanted vaccine and AS03 alone activated transient innate (neutrophils/eosinophils) immune responses. No serum cytokines were detected. CNS analyses revealed neither microglia activation nor inflammatory cellular infiltrates in the brain. No differences between treatment groups were detected for albumin extravascular leakage, CSF hypocretin levels, numbers of hypocretin-positive neuronal bodies or distributions of hypocretin-positive axonal/dendritic projections. Consequently, there was no evidence that intramuscular administration of the test articles promoted inflammation or damage in the CNS, or blood-brain barrier disruption, in this model. PMID:27629482

Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico.

PubMed

Elizarrarás-Rivas, Jesús; Vargas-Mendoza, Jaime E; Mayoral-García, Maurilio; Matadamas-Zarate, Cuauhtémoc; Elizarrarás-Cruz, Anaid; Taylor, Melanie; Agho, Kingsley

2010-12-03

The A/H1N1 pandemic originated in Mexico in April 2009, amid high uncertainty, social and economic disruption, and media reports of panic. The aim of this research project was to evaluate the psychological response of family primary caregivers of patients hospitalised in the Intensive Care Unit (ICU) with suspected influenza A/H1N1 to establish whether there was empirical evidence of high adverse psychological response, and to identify risk factors for such a response. If such evidence was found, a secondary aim was to develop a specific early intervention of psychological support for these individuals, to reduce distress and possibly lessen the likelihood of post-traumatic stress disorder (PTSD) in the longer term. Psychological assessment questionnaires were administered to the family primary caregivers of patients hospitalised in the ICU in the General Hospital of Zone 1 of the Mexican Institute for Social Security (IMSS), Oaxaca, Mexico with suspected influenza A/H1N1, during the month of November 2009. The main outcome measures were ratings of reported perceived stress (PSS-10), depression (CES-D), and death anxiety (DAQ). Data were subjected to simple and multiple linear regression analysis to identify risk factors for adverse psychological response. Elevated levels of perceived stress and depression, compared to population normative data, and moderate levels of death anxiety were noted. Levels of depression were similar to those found in comparable studies of family members of ICU patients admitted for other conditions. Multiple regression analysis indicated that increasing age and non-spousal family relationship were significantly associated with depression and perceived stress. Female gender, increasing age, and higher levels of education were significantly associated with high death anxiety. Comparisons with data collected in previous studies in the same hospital ICU with groups affected by a range of other medical conditions indicated that the

Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico

PubMed Central

2010-01-01

Background The A/H1N1 pandemic originated in Mexico in April 2009, amid high uncertainty, social and economic disruption, and media reports of panic. The aim of this research project was to evaluate the psychological response of family primary caregivers of patients hospitalised in the Intensive Care Unit (ICU) with suspected influenza A/H1N1 to establish whether there was empirical evidence of high adverse psychological response, and to identify risk factors for such a response. If such evidence was found, a secondary aim was to develop a specific early intervention of psychological support for these individuals, to reduce distress and possibly lessen the likelihood of post-traumatic stress disorder (PTSD) in the longer term. Methods Psychological assessment questionnaires were administered to the family primary caregivers of patients hospitalised in the ICU in the General Hospital of Zone 1 of the Mexican Institute for Social Security (IMSS), Oaxaca, Mexico with suspected influenza A/H1N1, during the month of November 2009. The main outcome measures were ratings of reported perceived stress (PSS-10), depression (CES-D), and death anxiety (DAQ). Data were subjected to simple and multiple linear regression analysis to identify risk factors for adverse psychological response. Results Elevated levels of perceived stress and depression, compared to population normative data, and moderate levels of death anxiety were noted. Levels of depression were similar to those found in comparable studies of family members of ICU patients admitted for other conditions. Multiple regression analysis indicated that increasing age and non-spousal family relationship were significantly associated with depression and perceived stress. Female gender, increasing age, and higher levels of education were significantly associated with high death anxiety. Comparisons with data collected in previous studies in the same hospital ICU with groups affected by a range of other medical conditions

Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh.

PubMed

Haider, N; Sturm-Ramirez, K; Khan, S U; Rahman, M Z; Sarkar, S; Poh, M K; Shivaprasad, H L; Kalam, M A; Paul, S K; Karmakar, P C; Balish, A; Chakraborty, A; Mamun, A A; Mikolon, A B; Davis, C T; Rahman, M; Donis, R O; Heffelfinger, J D; Luby, S P; Zeidner, N

2017-02-01

Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted 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 influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes 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. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate

Westward Spread of Highly Pathogenic Avian Influenza A(H7N9) Virus among Humans, China.

PubMed

Yang, Qiqi; Shi, Wei; Zhang, Lei; Xu, Yi; Xu, Jing; Li, Shen; Zhang, Junjun; Hu, Kan; Ma, Chaofeng; Zhao, Xiang; Li, Xiyan; Liu, Feng; Tong, Xin; Zhang, Guogang; Yu, Pengbo; Pybus, Oliver G; Tian, Huaiyu

2018-06-01

We report infection of humans with highly pathogenic avian influenza A(H7N9) virus in Shaanxi, China, in May 2017. We obtained complete genomes for samples from 5 patients and from live poultry markets or farms in 4 cities. Results indicate that H7N9 is spreading westward from southern and eastern China.

Benzo[a]pyrene activates an AhR/Src/ERK axis that contributes to CYP1A1 induction and stable DNA adducts formation in lung cells.

PubMed

Vázquez-Gómez, G; Rocha-Zavaleta, L; Rodríguez-Sosa, M; Petrosyan, P; Rubio-Lightbourn, J

2018-06-01

Benzo[a]pyrene (B[a]P), the most extensively studied carcinogen in cigarette smoke, has been regarded as a critical mediator of lung cancer. It is known that B[a]P-mediated Aryl hydrocarbon Receptor (AhR) activation stimulates the mitogen activated protein kinases (MAPK) signaling cascade in different cell models. MAPK pathway disturbances drive alterations in cellular processes, such as differentiation, proliferation, and apoptosis, and the disturbances may also modify the AhR pathway itself. However, MAPK involvement in B[a]P metabolic activation and toxicity in lung tissues is not well understood. Here, we used a non-transformed human bronchial epithelial lung cell line, BEAS-2B, to study the participation of ERK 1/2 kinases in the metabolic activation of B[a]P and in its related genotoxic effects. Our results indicate that B[a]P is not cytotoxic to BEAS-2B cells at relatively low concentrations, but it enhances CYP1A1 gene transcription and protein induction. Additionally, B[a]P promotes Src and ERK 1/2 phosphorylation. Accordingly, inhibition of both Src and ERK 1/2 phosphorylation decreases CYP1A1 protein induction, AhR nuclear translocation and production of B[a]P adducts. Together, these data suggest a crosstalk between AhR and the members of the MAPK pathway, ERK 1/2 mediated by Src kinase. This interaction is important for the adequate AhR pathway signaling that in turn induces transcription and protein induction of CYP1A1 and B[a]P-induced DNA damage in BEAS-2B cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

PubMed

Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène; Gudlaugsson, Ólafur; Hauge, Siri Helene; Lyytikäinen, Outi; Sigmundsdóttir, Guðrún; Tegnell, Anders; Virtanen, Mikko; Krause, Tyra Grove

2016-04-21

During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

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

PubMed

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

2015-05-01

European herring gull (Larus argentatus) eggs from two Norwegian islands, Musvær in the south east and Reiaren in Northern Norway, were screened for dioxins, furans, and dioxin-like and selected non-dioxin-like polychlorinated biphenyls (PCBs), and subjected to non-target analysis to try to identify the aryl hydrocarbon receptor (AhR) agonists, responsible for elevated levels measured using the dioxin responsive chemically activated luciferase expression (DR-CALUX) assay. Eggs from Musvær contained chemically calculated toxic equivalent (WHO TEQ) levels of between 109 and 483 pg TEQ/g lw, and between 82 and 337 pg TEQ/g lw was determined in eggs from Reiaren. In particular PCB126 contributed highly to the total TEQ (69-82%). In 19 of the 23 samples the calculated WHO TEQ was higher than the TEQCALUX. Using CALUX specific relative effect potencies (REPs), the levels were lower at between 77 and 292 pg/g lw in eggs from Musvær and between 55 and 223 pg/g lw in eggs from Reiaren, which was higher than the TEQCALUX in 16 of the 23 samples. However, the means of the REP values and the TEQCALUX were not significantly different. This suggests the presence of compounds that can elicit antagonist effects, with a low binding affinity to the AhR. Non-target analysis identified the presence of hexachlorobenzene (HCB) (quantified at 9.6-185 pg/g lw) but neither this compound nor high concentrations of PCB126 and non-dioxin-like PCBs could explain the differences between the calculated TEQ or REP values and the TEQCALUX. Even though, for most AhR agonists, the sensitivity of herring gulls is not known, the reported levels can be considered to represent a risk for biological effects in the developing embryo, compared to LC50 values in chicken embryos. For human consumers of herring gull eggs, these eggs contain TEQ levels up to four times higher than the maximum tolerable weekly intake. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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.

Possible Role of Songbirds and Parakeets in Transmission of Influenza A(H7N9) Virus to Humans

PubMed Central

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

2014-01-01

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. PMID:24572739

Treatment of fruit-juice industry wastewater in a two-stage anaerobic hybrid (AH) reactor system followed by a sequencing batch reactor (SBR).

PubMed

Tawfik, A; El-Kamah, H

2012-01-01

This study has been carried out to assess the performance of a combined system consisting of an anaerobic hybrid (AH) reactor followed by a sequencing batch reactor (SBR) for treatment of fruit-juice industry wastewater at a temperature of 26 degrees C. Three experimental runs were conducted in this investigation. In the first experiment, a single-stage AH reactor was operated at a hydraulic retention time (HRT) of 10.2 h and organic loading rate (OLR) of 11.8 kg COD m(-3) d(-1). The reactor achieved a removal efficiency of 42% for chemical oxygen demand (COD), 50.8% for biochemical oxygen demand (BOD5), 50.3% for volatile fatty acids (VFA) and 56.4% for total suspended solids (TSS). In the second experiment, two AH reactors connected in series achieved a higher removal efficiency for COD (67.4%), BOD5 (77%), and TSS (71.5%) at a total HRT of 20 h and an OLR of 5.9 kg COD m(-3) d(-1). For removal of the remaining portions of COD, BOD5 and TSS from the effluent of the two-stage AH system, a sequencing batch reactor (SBR) was investigated as a post-treatment unit. The reactor achieved a substantial reduction in total COD, resulting in an average effluent concentration of 50 mg L(-1) at an HRT of 11 h and OLR of 5.3 kg COD m(-3) d(-1). Almost complete removal of total BOD5 and oil and grease was achieved, i.e. 10 mg L(-1) and 1.2 mg L(-1), respectively, remained in the final effluent of the SBR.

Fuel conservation evaluation of US Army helicopters. Part 5. Ah-1S flight testing. Final report, 31 July-21 September 1982

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

Todd, L.L.; Savage, R.T.; Vincent, R.L.

1983-01-01

The United States Army Aviation Engineering Flight Activity conducted level flight performance tests of the AH-1S (Prod) helicopter to provide data to determine the most fuel efficient operating conditions. Hot and cold weather test sites were used to extend the range of the advancing tip Mach number data to supplement existing AH-1S performance data. Preliminary analysis of non-dimensional data identifies the effects of compressibility on performance and shows a power penalty of as much as 6% at a high NR/theta. The power required characteristics determined by these tests can be combined with engine performance to determine the most fuel efficientmore » operating conditions.« less

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

PubMed

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.

Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.

PubMed

Vesikari, Timo; Richardus, Jan Hendrik; Berglund, Johan; Korhonen, Tiina; Flodmark, Carl-Erik; Lindstrand, Ann; Silfverdal, Sven Arne; Bambure, Vinod; Caplanusi, Adrian; Dieussaert, Ilse; Roy-Ghanta, Sumita; Vaughn, David W

2015-07-01

During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.

Recruiting Black Americans in a Large Cohort Study: The Adventist Health Study-2 (AHS-2) Design, Methods and Participant Characteristics

PubMed Central

Herring, R. Patti; Butler, Terry; Hall, Sonja; Montgomery, Susanne B.; Fraser, Gary E.

2011-01-01

Objective The goal of the prospective Adventist Health Study-2 (AHS-2) was to examine the relationship between diet and risk of breast, prostate and colon cancers in Black and White participants. This paper describes the study design, recruitment methods, response rates, and characteristics of Blacks in the AHS-2, thus providing insights about effective strategies to recruit Blacks to participate in research studies. Design We designed a church-based recruitment model and trained local recruiters who used various strategies to recruit participants in their churches. Participants completed a 50-page self-administered dietary and lifestyle questionnaire. Participants Participants are Black Seventh-day Adventists, aged 30–109 years, and members of 1,209 Black churches throughout the United States and Canada. Results Approximately 48,328 Blacks from an estimated target group of over 90,000 signed up for the study and 25,087 completed the questionnaire, comprising about 26% of the larger 97,000 AHS-2-member cohort. Participants were diverse in age, geographic location, education, and income. Seventy percent were female with a median age of 59 years. Conclusion In spite of many recruitment challenges and barriers, we successfully recruited a large cohort whose data should provide some answers as to why Blacks have poorer health outcomes than several other ethnic groups, and help explain existing health disparities. PMID:21305834

Laboratory preparedness in EU/EEA countries for detection of novel avian influenza A(H7N9) virus, May 2013

PubMed Central

Broberg, E; Pereyaslov, D; Struelens, M; Palm, D; Meijer, A; Ellis, J; Zambon, M; McCauley, J; Daniels, R

2015-01-01

Following human infections with novel avian influenza A(H7N9) viruses in China, the European Centre for Disease Prevention and Control, the World Health Organization (WHO) Regional Office for Europe and the European Reference Laboratory Network for Human Influenza (ERLI-Net) rapidly posted relevant information, including real-time RT-PCR protocols. An influenza RNA sequence-based computational assessment of detection capabilities for this virus was conducted in 32 national influenza reference laboratories in 29 countries, mostly WHO National Influenza Centres participating in the WHO Global Influenza Surveillance and Response System (GISRS). Twenty-seven countries considered their generic influenza A virus detection assay to be appropriate for the novel A(H7N9) viruses. Twenty-two countries reported having containment facilities suitable for its isolation and propagation. Laboratories in 27 countries had applied specific H7 real-time RT-PCR assays and 20 countries had N9 assays in place. Positive control virus RNA was provided by the WHO Collaborating Centre in London to 34 laboratories in 22 countries to allow evaluation of their assays. Performance of the generic influenza A virus detection and H7 and N9 subtyping assays was good in 24 laboratories in 19 countries. The survey showed that ERLI-Net laboratories had rapidly developed and verified good capability to detect the novel A(H7N9) influenza viruses. PMID:24507469

Comparison of 2010-2011 H3N2 influenza A viruses isolated from swine and the A(H3N2)v isolated from humans in 2011

USDA-ARS?s Scientific Manuscript database

In the end of 2011, 12 U.S. cases of humans infected with swine H3N2 virus containing the matrix gene from pandemic H1N1 2009 virus (H1N1pdm09) were detected and named A(H3N2)v. This study used a swine model to compare the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2...

Performance features of 22-cell, 19Ah single pressure vessel nickel hydrogen battery

NASA Technical Reports Server (NTRS)

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.

Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands, December 2017.

PubMed

Beerens, Nancy; Koch, Guus; Heutink, Rene; Harders, Frank; Vries, D P Edwin; Ho, Cynthia; Bossers, Alex; Elbers, Armin

2018-04-17

A novel highly pathogenic avian influenza A(H5N6) virus affecting wild birds and commercial poultry was detected in the Netherlands in December 2017. Phylogenetic analysis demonstrated that the virus is a reassortant of H5N8 clade 2.3.4.4 viruses and not related to the Asian H5N6 viruses that caused human infections.

The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue.

PubMed

Knepper, Jessica; Schierhorn, Kristina L; Becher, Anne; Budt, Matthias; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Gruber, Achim D; Suttorp, Norbert; Schweiger, Brunhilde; Hippenstiel, Stefan; Hocke, Andreas C; Wolff, Thorsten

2013-10-08

A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to

Reassortant swine influenza viruses isolated in Japan contain genes from pandemic A(H1N1) 2009.

PubMed

Kanehira, Katsushi; Takemae, Nobuhiro; Uchida, Yuko; Hikono, Hirokazu; Saito, Takehiko

2014-06-01

In 2013, three reassortant swine influenza viruses (SIVs)-two H1N2 and one H3N2-were isolated from symptomatic pigs in Japan; each contained genes from the pandemic A(H1N1) 2009 virus and endemic SIVs. Phylogenetic analysis revealed that the two H1N2 viruses, A/swine/Gunma/1/2013 and A/swine/Ibaraki/1/2013, were reassortants that contain genes from the following three distinct lineages: (i) H1 and nucleoprotein (NP) genes derived from a classical swine H1 HA lineage uniquely circulating among Japanese SIVs; (ii) neuraminidase (NA) genes from human-like H1N2 swine viruses; and (iii) other genes from pandemic A(H1N1) 2009 viruses. The H3N2 virus, A/swine/Miyazaki/2/2013, comprised genes from two sources: (i) hemagglutinin (HA) and NA genes derived from human and human-like H3N2 swine viruses and (ii) other genes from pandemic A(H1N1) 2009 viruses. Phylogenetic analysis also indicated that each of the reassortants may have arisen independently in Japanese pigs. A/swine/Miyazaki/2/2013 were found to have strong antigenic reactivities with antisera generated for some seasonal human-lineage viruses isolated during or before 2003, whereas A/swine/Miyazaki/2/2013 reactivities with antisera against viruses isolated after 2004 were clearly weaker. In addition, antisera against some strains of seasonal human-lineage H1 viruses did not react with either A/swine/Gunma/1/2013 or A/swine/Ibaraki/1/2013. These findings indicate that emergence and spread of these reassortant SIVs is a potential public health risk. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

PubMed Central

Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

2014-01-01

Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

Highly Pathogenic Avian Influenza A(H5N8) Virus in Wild Migratory Birds, Qinghai Lake, China.

PubMed

Li, Mingxin; Liu, Haizhou; Bi, Yuhai; Sun, Jianqing; Wong, Gary; Liu, Di; Li, Laixing; Liu, Juxiang; Chen, Quanjiao; Wang, Hanzhong; He, Yubang; Shi, Weifeng; Gao, George F; Chen, Jianjun

2017-04-01

In May 2016, a highly pathogenic avian influenza A(H5N8) virus strain caused deaths among 3 species of wild migratory birds in Qinghai Lake, China. Genetic analysis showed that the novel reassortant virus belongs to group B H5N8 viruses and that the reassortment events likely occurred in early 2016.

Validation test of 125 Ah advanced design IPV nickel-hydrogen flight cells

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Hall, Stephen W.

1993-01-01

An update of validation test results confirming the advanced design nickel-hydrogen cell is presented. An advanced 125 Ah individual pressure vessel (IPV) nickel-hydrogen cell was designed. The primary function of the advanced cell is to store and deliver energy for long-term, Low-Earth-Orbit (LEO) spacecraft missions. The new features of this design, which are not incorporated in state-of-the-art design cells, are: (1) use of 26 percent rather than 31 percent potassium hydroxide (KOH) electrolyte; (2) use of a patented catalyzed wall wick; (3) use of serrated-edge separators to facilitate gaseous oxygen and hydrogen flow within the cell, while still maintaining physical contact with the wall wick for electrolyte management; and (4) use of a floating rather than a fixed stack (state-of-the-art) to accommodate nickel electrode expansion due to charge/discharge cycling. The significant improvements resulting from these innovations are extended cycle life; enhanced thermal, electrolyte, and oxygen management; and accommodation of nickel electrode expansion. Six 125 Ah flight cells based on this design were fabricated by Eagle-Picher. Three of the cells contain all of the advanced features (test cells) and three are the same as the test cells except they do not have catalyst on the wall wick (control cells). All six cells are in the process of being evaluated in a LEO cycle life test at the Naval Weapons Support Center, Crane, IN, under a NASA Lewis Research Center contract. The catalyzed wall wick cells have been cycled for over 19000 cycles with no cell failures in the continuing test. Two of the noncatalyzed wall wick cells failed (cycles 9588 and 13,900).

Seroevidence for a High Prevalence of Subclinical Infection With Avian Influenza A(H5N1) Virus Among Workers in a Live-Poultry Market in Indonesia

PubMed Central

Shimizu, Kazufumi; Wulandari, Laksmi; Poetranto, Emmanuel D.; Setyoningrum, Retno A.; Yudhawati, Resti; Sholikhah, Amelia; Nastri, Aldise M.; Poetranto, Anna L.; Candra, Adithya Y. R.; Puruhito, Edith F.; Takahara, Yusuke; Yamagishi, Yoshiaki; Yamaoka, Masaoki; Hotta, Hak; Ustumi, Takako; Lusida, Maria I.; Soetjipto; Shimizu, Yohko K.; Soegiarto, Gatot; Mori, Yasuko

2016-01-01

Background. In Indonesia, highly pathogenic avian influenza A(H5N1) virus has become endemic in poultry and has caused sporadic deadly infections in human. Since 2012, we have conducted fixed-point surveillance of avian influenza viruses at a live-poultry market in East Java, Indonesia. In this study, we examined the seroprevalence of avian influenza A(H5N1) virus infection among market workers. Methods. Sera were collected from 101 workers in early 2014 and examined for antibody activity against avian A(H5N1) Eurasian lineage virus by a hemagglutination-inhibition (HI) assay. Results. By the HI assay, 84% of the sera tested positive for antibody activity against the avian virus. Further analysis revealed that the average HI titer in 2014 was 2.9-fold higher than in 2012 and that seroconversion occurred in 44% of paired sera (11 of 25) between 2012 and 2014. A medical history survey was performed in 2016; responses to questionnaires indicated that none of workers had had severe acute respiratory illness during 2013. Conclusions. This study provides evidence of a high prevalence of avian A(H5N1) virus infection in 2013 among workers at a live-poultry market. However, because no instances of hospitalizations were reported, we can conclude the virus did not manifest any clinical symptoms in workers. PMID:27923953

Ultraviolet B inhibition of DNMT1 activity via AhR activation dependent SIRT1 suppression in CD4+ T cells from systemic lupus erythematosus patients.

PubMed

Wu, Zhouwei; Mei, Xingyu; Ying, Zuolin; Sun, Yue; Song, Jun; Shi, Weimin

2017-06-01

Previous studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE. However, the exact mechanisms by which DNMT1 activity is inhibited by UVB in lupus CD4+ T cells remain largely unknown. To elucidate the exact mechanisms by which DNMT1 activity is inhibited by UVB in lupus CD4+ T cells. Twenty-two newly diagnosed active SLE patients and 30 healthy controls were enrolled in the study. CD4+ T cells were isolated, cultured and treated. DNMT1 activity assay, quantitative real-time PCR (qRT-PCR), Western blotting, RNA interference using small interfering RNA and Chromatin Immunoprecipitation (ChIP) assay were employed. DNMT1 activity was inhibited in si-SIRT1-transfected CD4+ T cells, and increased by the established SIRT1 activator, SRT1720. Moreover, the mRNA and protein expression of SIRT1 were suppressed by UVB exposure in lupus CD4+ T cells. UVB-inhibited DNMT1 activity was reversed by SRT1720 in si-control-transfected lupus CD4+ T cells, but not in si-SIRT1-transfected lupus CD4 + T cells. Furthermore, AhR activation by VAF347 reduced the mRNA and protein expression of SIRT1. ChIP using an antibody against AhR in normal CD4+ T cells revealed a 16-fold stronger signal at the site about 1.6kb upstream from the translation start site of the SIRT1 promoter. Finally, UVB could activate AhR and inhibit the mRNA and protein expression of SIRT1. AhR knockdown abrogated the inhibition of UVB-mediated SIRT1 mRNA and protein expression and DNMT1 activity in lupus CD4+ T cells. UVB suppressed SIRT1 expression via activating AhR, and subsequently inhibited DNMT1

A/H1N1 Vaccine Intentions in College Students: An Application of the Theory of Planned Behavior

ERIC Educational Resources Information Center

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…

Results of deep DoD life cycle tests at high rates on 12Ah NiCd cells

NASA Technical Reports Server (NTRS)

Panneton, Paul E.; Meyer, John R.

1992-01-01