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Sample records for ah ah ah

  1. AH Her Observing Campaign

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2013-05-01

    Dr. Juan Echevarria (Universidad Nacional Autónoma de México) and colleagues request AAVSO assistance in a campaign on the Z Cam-type cataclysmic variable AH Her being carried out 2013 May 29 - June 18. They will be making photometric and spectroscopic observations of AH Her using the 2.1m and 0.84m telescopes at San Pedro Martir Observatory (SPM). Their goal is to carry out a radial velocity study of the system components using modern detectors; no study of AH Her has been made since the one by Horne, Wade, and Szkody in 1980-1981 (1986MNRAS.219..791H). Photometry and spectroscopy are requested. AH Her, for decades a reasonably "regular" Z Cam system, began exhibiting significantly anomalous behavior in ~2007. Since then it has experienced brief periods of fairly typical behavior interspersed with more anomalous intervals, including some unprecedented behavior. Most recently, it has returned to a more normal pattern of outbursts shape-wise but it is not back to its normal amplitude or frequency. AAVSO data will be essential for correlation in order to determine the precise time(s) of minimum occurring during the campaign. Finder charts with sequences may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

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

    SciTech Connect

    Monterrosa, Manuel Ernesto

    1996-01-24

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

  3. RESULTS FROM THE AHS PESTICIDE EXPOSURE STUDY

    EPA Science Inventory

    The Agricultural Health Study/Pesticide Exposure Study (AHS/PES) measured exposures resulting from agricultural use of 2,4-D and chlorpyrifos for a subset of applicators in the AHS cohort. Through on-farm measurements and observations, data collected in the exposure study will...

  4. AhR signalling and dioxin toxicity.

    PubMed

    Sorg, Olivier

    2014-10-15

    Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years. Although TCDD has been classified by the WHO as a human carcinogen, its carcinogenic potential to humans is not clearly demonstrated. It was first believed that AhR activation accounted for most, if not all, biological properties of dioxins. However, certain AhR agonists found in vegetables do not induce chloracne, and other chemicals, in particular certain therapeutic agents, may induce a chloracne-like syndrome without activating AhR. It is time to rethink the mechanism of dioxin toxicity and analyse in more details the biological events following exposure to these compounds and other AhR agonists, some of which have a very different chemical structure than TCDD. In particular various food-containing AhR agonists are non-toxic and may on the contrary have beneficial properties to human health. PMID:24239782

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  6. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  7. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  8. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  9. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  10. Ah receptor ligands in tobacco smoke.

    PubMed

    Löfroth, G; Rannug, A

    1988-08-01

    Tar particulates from cigarette smoke contain compounds with affinity for the Ah receptor. The sidestream activity is larger than that of the mainstream with a ratio of about 5. The compounds causing the affinity appear in the neutral fraction after chemical fractionation excluding basic and acidic components as major contributors to the affinity. The affinity cannot be explained by benzo[a]pyrene and other polycyclic aromatic hydrocarbons but it might be caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and by oxidized tryptophan derivatives.

  11. Newspapers and newspaper ink contain agonists for the ah receptor.

    PubMed

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

    2008-04-01

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

  12. 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

  13. 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.

  14. Performance of AEA 80 Ah Battery under GEO Profiles

    NASA Technical Reports Server (NTRS)

    Russel, N.; Curzon, D.; Ng, K.; Lee, L.; Rao, G.

    2004-01-01

    This viewgraph presentation is divided into the following sections: 1) AEA Geosynchronous Earth Orbit (GEO) Life Testing; 2) AEA/Goddard Space Flight Center (GSFC) 20 Ah Battery; 3) AEA/GSFC 80 Ah Battery; 4) Solar Dynamic Observatory (SDO) Life Test; 5) Test Results; 6) Correlation; 7) Conclusions.

  15. Induction of AhR-Mediated Gene Transcription by Coffee

    PubMed Central

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

    2014-01-01

    Background Aryl hydrocarbon receptor (AhR) is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells. Methods HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS) or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses. Results All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum. Conclusions By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health. PMID:25007155

  16. AH-1S communication switch integration program

    NASA Technical Reports Server (NTRS)

    Haworth, Loran; Szoboszlay, Zoltan; Shively, Robert; Bick, Frank J.

    1989-01-01

    The C-6533/ARC communication system as installed on the test AH-1E Cobra helicopter was modified to allow discrete radio selection of all aircraft radios at the cyclic radio/intercommunication system switch. The current Cobra-fleet use of the C-6533 system is cumbersome, particularly during low-altitude operations. Operationally, the current system C-6533 configuration and design requires the pilot to estimate when he can safely remove his hand from an active flight control to select radios during low-altitude flight. The pilot must then physically remove his hand from the flight control, look inside the cockpit to select and verify the radio selection and then effect the selected radio transmission by activating the radio/ICS switch on the cyclic. This condition is potentially hazardous, especially during low-level flight at night in degraded weather. To improve pilot performance, communications effectiveness, and safety, manprint principles were utilized in the selection of a design modification. The modified C-6533 design was kept as basic as possible for potential Cobra-fleet modification. The communications system was modified and the design was subsequently flight-tested by the U.S. Army Aeroflightdynamics Directorate and NASA at the NASA Ames Research Center, Mountain View, California. The design modification enables the Cobra pilot to maintain hands-on flight controls while selecting radios during nap-of-the-Earth (NOE) flight without looking inside the cockpit which resulted in reduced pilot workload ratings, better pilot handling quality ratings and increased flight safety for the NOE flight environment.

  17. Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue.

    PubMed

    Silkworth, J B; Antrim, L A; Sack, G

    1986-12-01

    Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue.

  18. NOAA 26.5 Ah LEO characterization test

    NASA Technical Reports Server (NTRS)

    Morrow, G. W.

    1986-01-01

    The General Electric (GE) 26.5 Ah NOAA-G flight nickel-cadmium cells were obtained from RCA-Astro Electronics to undergo performance characterization testing at the Goddard Space Flight Center (GSFC). This lot of cells was manufactured with passivated positive plate, to control nickel structure attack duing active material impregnation, and less electrolyte than normal (less than 3cc/Ah). The cells were tested in a parametric low Earth orbit (LEO) cycling regime that was previously used to test and characterize standard 50 Ah cells. Life cycle testing at the Naval Weapons Support Center (NWSC), in Crane, followed. The results of the test showed nominal performance in comparison with previous test data on the standard 50. Life cycle testing in the NOAA orbital regime is continuing at NWSC.

  19. Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity

    PubMed Central

    Vogel, Christoph F.A.; Chang, W.L. William; Kado, Sarah; McCulloh, Kelly; Vogel, Helena; Wu, Dalei; Haarmann-Stemmann, Thomas; Yang, GuoXiang; Leung, Patrick S.C.; Matsumura, Fumio; Gershwin, M. Eric

    2016-01-01

    Background: The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo. Objective: This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand. Methods: We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry. Results: AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL)-1β, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1β, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD. Conclusion: In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD. Citation: Vogel CF, Chang WL, Kado S, McCulloh K, Vogel H, Wu D, Haarmann-Stemmann T, Yang GX, Leung PS, Matsumura F

  20. 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.

  1. CCD Photometric Study and Period Investigation of AH Tauri

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  2. 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...

  3. 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

    2014-01-01

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

  4. An orbital period for the dwarf nova AH Herculis

    NASA Astrophysics Data System (ADS)

    Moffat, A. F. J.; Shara, M. M.

    1984-07-01

    AH Her is the best-studied dwarf nova which displays rapid coherent oscillations at maximum light, yet its orbital period is not determined. Eleven nights of observations with the 1-meter Wise Observatory telescope with chopping secondary, and 'Nather' photometer, yield a period P = 0.247 + or - 0.008 day, in excellent agreement with that predicted from the decline rate of the outburst. The source of flickering in the system (presumably the hot spot) is shown to fluctuate with the same amplitude whether AH Her is in outburst or not. The implication is that the accretion stream, hot spot, and outer disk are unaffected by, and do not take part in the eruption.

  5. Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus

    PubMed Central

    Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F.

    2015-01-01

    Background Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. Study design We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Results Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 104/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. Conclusions It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. PMID:26590689

  6. Functional Conservation and Divergence of Four Ginger AP1/AGL9 MADS–Box Genes Revealed by Analysis of Their Expression and Protein–Protein Interaction, and Ectopic Expression of AhFUL Gene in Arabidopsis

    PubMed Central

    Song, Juanjuan; Sun, Wei; Xia, Kuaifei; Liao, Jingping; Zhang, Mingyong

    2014-01-01

    Alpinia genus are known generally as ginger–lilies for showy flowers in the ginger family, Zingiberaceae, and their floral morphology diverges from typical monocotyledon flowers. However, little is known about the functions of ginger MADS–box genes in floral identity. In this study, four AP1/AGL9 MADS–box genes were cloned from Alpinia hainanensis, and protein–protein interactions (PPIs) and roles of the four genes in floral homeotic conversion and in floral evolution are surveyed for the first time. AhFUL is clustered to the AP1lineage, AhSEP4 and AhSEP3b to the SEP lineage, and AhAGL6–like to the AGL6 lineage. The four genes showed conserved and divergent expression patterns, and their encoded proteins were localized in the nucleus. Seven combinations of PPI (AhFUL–AhSEP4, AhFUL–AhAGL6–like, AhFUL–AhSEP3b, AhSEP4–AhAGL6–like, AhSEP4–AhSEP3b, AhAGL6–like–AhSEP3b, and AhSEP3b–AhSEP3b) were detected, and the PPI patterns in the AP1/AGL9 lineage revealed that five of the 10 possible combinations are conserved and three are variable, while conclusions cannot yet be made regarding the other two. Ectopic expression of AhFUL in Arabidopsis thaliana led to early flowering and floral organ homeotic conversion to sepal–like or leaf–like. Therefore, we conclude that the four A. hainanensis AP1/AGL9 genes show functional conservation and divergence in the floral identity from other MADS–box genes. PMID:25461565

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

    PubMed

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

    2015-01-01

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

  8. 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.

  9. 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.

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

    PubMed

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

    2015-10-15

    The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P = .01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.

  11. 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).

  12. 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.

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

    PubMed

    Millman, Alexander J; 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

    2015-05-01

    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.

  14. 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

  15. 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

  16. Attack helicopter (AH-1T) cockpit systems integration

    NASA Technical Reports Server (NTRS)

    Graf, V. A.

    1984-01-01

    This discussion summarizes the effort conducted by the BHTI Human Factors and Cockpit Arrangement group for a study and design of the integration of a cockpit control system for the AH 1T (TOW). The resulting design is a culmination of studies that were conducted using the existing configuration as a baseline and complementing it with new equipment and subsystems that fulfill the attack helicopter requirements for the foreseeable future. Of primary concern was the requirement to add a missile control system, with secondary considerations for improved NOE and night operations. In addition, growth capabilities for improved target acquisition, weapons delivery, and precise navigation was considered. Along with the addition of new equipment, the aircraft was assumed to have a central multiplex data bus system for information transfer throughout the aircraft and its subsystems.

  17. Human Infection with Highly Pathogenic A(H7N7) Avian Influenza Virus, Italy, 2013

    PubMed Central

    Rossini, Giada; Facchini, Marzia; Vaccari, Gabriele; Di Trani, Livia; Di Martino, Angela; Gaibani, Paolo; Vocale, Caterina; Cattoli, Giovanni; Bennett, Michael; McCauley, John W.; Rezza, Giovanni; Moro, Maria Luisa; Rangoni, Roberto; Finarelli, Alba Carola; Landini, Maria Paola; Castrucci, Maria Rita; Donatelli, Isabella

    2014-01-01

    During an influenza A(H7N7) virus outbreak among poultry in Italy during August–September 2013, infection with a highly pathogenic A(H7N7) avian influenza virus was diagnosed for 3 poultry workers with conjunctivitis. Genetic analyses revealed that the viruses from the humans were closely related to those from chickens on affected farms. PMID:25271444

  18. 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

  19. 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.

  20. 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.…

  1. 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

  2. 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. PMID:25797602

  3. Precursor systems analyses of automated highway systems. Activity area K AHS roadway operational analysis. Final report, September 1993-November 1994

    SciTech Connect

    Schulze, R.; Roper, D.; Tsao, J.; Michael, B.

    1995-05-01

    This study considers the roadway operational requirements of an automated highway system (AHS) in light of corresponding operational requirements for existing conventional highways with traffic operations centers (TOCs). Contrasts and similarities between TOC and AHS operations are identified. Maintenance operations and activities are the focus of the study. Similarities and contrasts between AHS and conventional highways are considered, analyzed, and discussed to raise issues risks. Urban/rural, passenger/heavy vehicle, and representative system configuration differences are covered insofar as there are significant differences among these categories of possible AHS operations. Maintenance needs and incident response requirements as they would impact as AHS operating agency are qualitatively analyzed. Two possible staged deployment scenarios for AHS are presented. The fault tolerance of the AHS is assessed. Results of interviews with personnel in charge of several existing TOCs have been summarized. The role of the driver in an AHS is discussed.

  4. Induction of human UGT1A1 by bilirubin through AhR dependent pathway.

    PubMed

    Togawa, Hiroshi; Shinkai, Shigeko; Mizutani, Takaharu

    2008-12-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) plays a key role to conjugate bilirubin and preventing jaundice, but there is no report showing the induction of human UGT1A1 (UGT1A1) by bilirubin. In this report, we show findings of the induction of the reporter gene (-3475/+14) of UGT1A1 in HepG2 cells by bilirubin at 50 microM, 100 microM, with human aryl hydrocarbon receptor (hAhR). We confirmed that induction of the reporter gene by bilirubin is dependent on the position of the xenobiotic responsive element (XRE) (-3328/-3319) of UGT1A1, because the XRE deletion UGT1A1 gene did not respond to stimulation by a complex of bilirubin and hAhR. alpha-Naphthoflavone (alpha-NF) of a typical AhR antagonist at 50 microM inhibited induction by bilirubin, suggesting that bilirubin stimulates through binding with hAhR. Meanwhile, bilirubin itself did not stimulate the induction of AhR, because we detected no-elevation of the mRNA level of AhR by RT-PCR. These results indicate that the induction of UGT1A1 by bilirubin-AhR did not depend on the elevation of AhR but on ligand binding. From this result, we considered that high bilirubin in neonates must induce the elevation of UGT1A1 after birth to prevent jaundice, and bilirubin in adults also regulates the level of UGT1A1. This is the first report showing direct induction of UGT1A1 by a bilirubin through AhR pathway. PMID:19356098

  5. The 50 Ah NiH2 CPV qualification tests

    NASA Technical Reports Server (NTRS)

    Garner, J. C.; Barnes, Wilbert L.; Hickman, Gary L.

    1995-01-01

    In 1992, the Naval Research Laboratory (NRL) started a program to qualify a large diameter common pressure vessel (CPV) nickel-hydrogen (NiH2) batteries for use on future Navy/NRL spacecraft electrical power subsystems. NRL's involvement with the qualification of CPV NiH2 batteries dates back to 1988 when COMSAT and Johnson Controls, Inc. initiated a joint effort to fly the first ever NiH2 CPV in space. A later NRL-JCI cooperative research and development agreement led to the launch of a space experiment in 1993 and to the use of a single NiH2 CPV battery on the BMDO Clementine spacecraft in 1994. NRL initiated procurement of two, 50 Ah CPV NiH2 batteries in the Fall of 1992. The two batteries were delivered to NRL in June 1994. NiH2 CPV batteries have almost 2x the specific energy (Wh/kg) of nickel cadium batteries and 2x the energy density (Wh/l) of individual pressure vessel NiH2 CPV's. This presentation discusses the results of electrical and mechanical qualification tests conducted at NRL. The tests included electrical characterization, standard capacity, random vibration, peak load, and thermal vacuum. The last slides of the presentation show initial results from the life cycle tests of the second NiH2 CPV battery at 40% depth of discharge and a temperature of 10 C.

  6. The 50 Ah NiH2 CPV qualification tests

    NASA Astrophysics Data System (ADS)

    Garner, J. C.; Barnes, Wilbert L.; Hickman, Gary L.

    1995-02-01

    In 1992, the Naval Research Laboratory (NRL) started a program to qualify a large diameter common pressure vessel (CPV) nickel-hydrogen (NiH2) batteries for use on future Navy/NRL spacecraft electrical power subsystems. NRL's involvement with the qualification of CPV NiH2 batteries dates back to 1988 when COMSAT and Johnson Controls, Inc. initiated a joint effort to fly the first ever NiH2 CPV in space. A later NRL-JCI cooperative research and development agreement led to the launch of a space experiment in 1993 and to the use of a single NiH2 CPV battery on the BMDO Clementine spacecraft in 1994. NRL initiated procurement of two, 50 Ah CPV NiH2 batteries in the Fall of 1992. The two batteries were delivered to NRL in June 1994. NiH2 CPV batteries have almost 2x the specific energy (Wh/kg) of nickel cadium batteries and 2x the energy density (Wh/l) of individual pressure vessel NiH2 CPV's. This presentation discusses the results of electrical and mechanical qualification tests conducted at NRL. The tests included electrical characterization, standard capacity, random vibration, peak load, and thermal vacuum. The last slides of the presentation show initial results from the life cycle tests of the second NiH2 CPV battery at 40% depth of discharge and a temperature of 10 C.

  7. Non-dioxin-like AhR ligands in a mouse peanut allergy model.

    PubMed

    Schulz, Veronica J; Smit, Joost J; Huijgen, Veerle; Bol-Schoenmakers, Marianne; van Roest, Manon; Kruijssen, Laura J W; Fiechter, Daniëlle; Hassing, Ine; Bleumink, Rob; Safe, Stephen; van Duursen, Majorie B M; van den Berg, Martin; Pieters, Raymond H H

    2012-07-01

    Recently, we have shown that AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses sensitization to peanut at least in part by inducing a functional shift toward CD4(+)CD25(+)Foxp3(+) T cells. Next to TCDD, numerous other AhR ligands have been described. In this study, we investigated the effect of three structurally different non-dioxin-like AhR ligands, e.g., 6-formylindolo[3,2-b]carbazole (FICZ), β-naphthoflavone (β-NF), and 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF), on peanut sensitization. Female C57BL/6 mice were sensitized by administering peanut extract (PE) by gavage in the presence of cholera toxin. Before and during peanut sensitization, mice were treated with FICZ, β-NF, or 6-MCDF. AhR gene transcription in duodenum and liver was investigated on day 5, even as the effect of these AhR ligands on CD4(+)CD25(+)Foxp3(+) T(reg) cells in spleen and mesenteric lymph nodes (MLNs). Mice treated with TCDD were included as a positive control. Furthermore, the murine reporter cell line H1G1.1c3 (CAFLUX) was used to investigate the possible role of metabolism of TCDD, FICZ, β-NF, and 6-MCDF on AhR activation in vitro. TCDD, but not FICZ, β-NF, and 6-MCDF, suppressed sensitization to peanut (measured by PE-specific IgE, IgG1, IgG2a and PE-induced interleukin (IL)-5, IL-10, IL-13, IL-17a, IL-22, and interferon-γ). In addition, FICZ, β-NF, and 6-MCDF treatments less effectively induced AhR gene transcription (measured by gene expression of AhR, AhRR, CYP1A1, CYP1A2, CYP1B1) compared with TCDD-treated mice. Furthermore, FICZ, β-NF and 6-MCDF did not increase the percentage of CD4(+)CD25(+)Foxp3(+) T(reg) cells in spleen and mesenteric lymph nodes compared with PE-sensitized mice, in contrast to TCDD. Inhibition of metabolism in vitro increased AhR activation. Together, these data shows that TCDD, but not FICZ, β-NF, and 6-MCDF suppresses sensitization to peanut. Differences in metabolism, AhR binding and subsequent gene transcription might

  8. Avian Influenza A(H5N1) and A(H9N2) Seroprevalence and Risk Factors for Infection Among Egyptians: A Prospective, Controlled Seroepidemiological Study

    PubMed Central

    Gomaa, Mokhtar R.; Kayed, Ahmed S.; Elabd, Mona A.; Zeid, Dina Abu; Zaki, Shaimaa A.; El Rifay, Amira S.; Sherif, Lobna S.; McKenzie, Pamela P.; Webster, Robert G.; Webby, Richard J.; Ali, Mohamed A.; Kayali, Ghazi

    2015-01-01

    Background. A(H5N1) and A(H9N2) avian influenza viruses are enzootic in Egyptian poultry, and most A(H5N1) human cases since 2009 have occurred in Egypt. Our understanding of the epidemiology of avian viruses in humans remains limited. Questions about the frequency of infection, the proportion of infections that are mild or subclinical, and the case-fatality rate remain largely unanswered. Methods. We conducted a 3-year, prospective, controlled, seroepidemiological study that enrolled 750 poultry-exposed and 250 unexposed individuals in Egypt. Results. At baseline, the seroprevalence of anti-A(H5N1) antibodies (titer, ≥80) among exposed individuals was 2% significantly higher than that among the controls (0%). Having chronic lung disease was a significant risk factor for infection. Antibodies against A(H9N2) were not detected at baseline when A(H9N2) was not circulating in poultry. At follow-up, A(H9N2) was detected in poultry, and consequently, the seroprevalence among exposed humans was between 5.6% and 7.5%. Vaccination of poultry, older age, and exposure to ducks were risk factors for A(H9N2) infection. Conclusions. Results of this study indicate that the number of humans infected with avian influenza viruses is much larger than the number of reported confirmed cases. In an area where these viruses are enzootic in the poultry, human exposure to and infection with avian influenza becomes more common. PMID:25355942

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2014-05-01

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

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

    NASA Astrophysics Data System (ADS)

    De Miguel, Eduardo; Jiménez, Marcos; Pérez, Irene; de la Cámara, Óscar G.

    2015-12-01

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

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Phylodynamics of influenza A(H3N2) in South America, 1999-2012.

    PubMed

    Born, Priscila Silva; Siqueira, Marilda Mendonça; Faria, Nuno Rodrigues; Resende, Paola Cristina; Motta, Fernando Couto; Bello, Gonzalo

    2016-09-01

    The limited influenza A(H3N2) genetic data available from the Southern Hemisphere (particularly from Africa and Latin America), constrains the accurate reconstruction of viral dissemination dynamics within those regions. Our objective was to describe the spatial dissemination dynamics of influenza A(H3N2) within South America. A total of 469 sequences of the HA1 portion of the hemagglutinin gene (HA) from influenza A(H3N2) viruses sampled in temperate and tropical South American countries between 1999 and 2012 were combined with available contemporary sequences from Australia, Hong Kong, United Kingdom and the United States. Phylogenetic analyses revealed that influenza A(H3N2) sequences from South America were highly intermixed with sequences from other geographical regions, although a clear geographic virus population structure was detected globally. We identified 14 clades mostly (≥80%) composed of influenza sequences from South American countries. Bayesian phylogeographic analyses of those clades support a significant role of both temperate and tropical regions in the introduction and dissemination of new influenza A(H3N2) strains within South America and identify an intensive bidirectional viral exchange between different geographical areas. These findings indicate that seasonal influenza A(H3N2) epidemics in South America are seeded by both the continuous importation of viral variants from other geographic regions and the short-term persistence of local lineages. This study also supports a complex metapopulation model of influenza A(H3N2) dissemination in South America, with no preferential direction in viral movement between temperate and tropical regions. PMID:27275847

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

    PubMed Central

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

    2015-01-01

    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. PMID:26615216

  19. 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.

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

    PubMed

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

    2015-08-01

    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.

  1. Studies on the role of the Ah receptor in hexachloro-benzene-induced porphyria

    SciTech Connect

    Hahn, M.E.

    1987-01-01

    Many of the effects of hexachlorobenzene (HCB) resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), whose effects are initiated by its binding to the AH receptor, the regulatory gene product of the Ah locus. I investigated the ability of HCB to interact with the AH receptor and the involvement of this protein in HCB-induced porphyria. The induction of two cytochrome P450 isozymes regulated by the Ah locus was also examined in light of their possible role in the pathogenesis of HCB- and TCDD-induced porphyria. HCB competitively inhibited the in vitro specific binding of ({sup 3}H)-TCDD to the rat hepatic Ah receptor (K{sub I} = 2.1 {mu}M) without affecting the solubility of ({sup 3}H)TCDD. Following the administration of HCB to rats, the number of ({sup 3}H)TCDD specific binding sites was reduced by up to 40%. HCB induced cytochromes P450b, P450e, P450c, and P450d, confirming that it is a mixed-type P450 inducer. The presence of porphyria in mice was assessed by measuring urinary and hepatic porphyrins and hepatic uroporphyrinogen decarboxylase activity.

  2. Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

    PubMed Central

    Herfst, Sander; Schrauwen, Eefje J. A.; Linster, Martin; Chutinimitkul, Salin; de Wit, Emmie; Munster, Vincent J.; Sorrell, Erin M.; Bestebroer, Theo M.; Burke, David F.; Smith, Derek J.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.

    2016-01-01

    Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza. PMID:22723413

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

    PubMed

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

    2016-01-01

    The aim of the present study was to verify the long-term cytotoxic effects of the MTA Fillapex and to compare them with AH Plus. Dissolution rate and pH were also evaluated. Human osteoblast cells were incubated with elutes of fresh specimens from AH Plus and MTA Fillapex, and with elutes of the same specimens for 4 successive weeks. Elute's pH was evaluated at each time point. A multiparametric cell viability assay was performed. For dissolution rate, ISO methodology was used. The results were analyzed by one-way analysis of variance, complemented with the Tukey post-test (p<0.05). No significant difference was found among the materials when fresh mixed (p>0.05). After 1 week, AH Plus became non-cytotoxic on all three evaluated parameters. Conversely, MTA Fillapex remained severely and mildly cytotoxic over the entire experimental period (p<0.05). The dissolution rate of AH Plus was significantly lower than MTA Fillapex at all time points (p>0.05). The pH of AH Plus was significantly lower than MTA Fillapex at the second and third week (p<0.05). In the other tested time points no statistical difference was observed. In conclusion, MTA Fillapex remained cytotoxic after 4 weeks and its cytotoxicity may be related to the high dissolution rate of this material. PMID:27652704

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

    Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health. PMID:26558458

  6. 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. PMID:18762178

  7. AhR expression and polymorphisms are associated with risk of coronary arterial disease in Chinese population

    PubMed Central

    Huang, Shian; Shui, Xiaorong; He, Yuan; Xue, Yiqiang; Li, Jianwen; Li, Guoming; Lei, Wei; Chen, Can

    2015-01-01

    The aryl hydrocarbon receptor (AhR) mediates the control of environmental toxicity, and modulates the development and pathogenesis of the cardiovascular system. However, little is known about the role of AhR in coronary arterial disease (CAD) susceptibility. We therefore conducted a case-control study in a Chinese population, and assessed the potential association between AhR variants and CAD susceptibility. Compared with the controls, circulating AhR expression was found to be significantly increased in patients with CAD and its subtypes including ST-segment and non-ST-segment elevation myocardial infarction, and stable and unstable angina pectoris. Receiver operating characteristic (ROC) analysis to evaluate the effect of AhR on CAD progression showed it to be a potent biomarker for CAD. Genotype frequencies of AhR rs2066853 differed significantly between CAD and control subjects, while smoking and hyperlipidemia markedly promoted CAD risk relative to the AhR polymorphism. Moreover, a significant difference in AhR variant distribution was observed between the four CAD subtypes with different severities. The expression level and functional polymorphisms of circulating AhR may affect the susceptibility and progression of CAD in Chinese populations. This provides a novel view of the etiology and epidemiology of CAD, and will contribute to the diagnosis and therapy of this severe disease. PMID:25620626

  8. Physicochemical properties and surfaces morphologies evaluation of MTA FillApex and AH plus.

    PubMed

    Borges, Álvaro Henrique; Orçati Dorileo, Maura Cristiane Gonçales; Dalla Villa, Ricardo; Borba, Alexandre Meireles; Semenoff, Tereza Aparecida Delle Vedove; Guedes, Orlando Aguirre; Estrela, Cyntia Rodrigues Araújo; Bandeca, Matheus Coelho

    2014-01-01

    The solubility, pH, electrical conductivity, and radiopacity of AH Plus and MTA FillApex were evaluated. In addition, the surfaces morphologies of the sealers were analyzed by using scanning electron microscopy. For pH test, the samples were immersed in distilled water at different periods of time. The same solution was used for electrical conductivity measurement. The solubility and radiopacity were evaluated according to ANSI/ADA. Statistical analyses were carried out at 5% level of significance. MTA FillApex presented higher mean value for solubility and electrical conductivity. No significant difference was observed in the mean values for pH reading. AH Plus presented higher radiopacity mean values. MTA FillApex presented an external surface with porosities and a wide range of sizes. In conclusion, the materials fulfill the ANSI/ADA requirements when considering the radiopacity and solubility. AH Plus revealed a compact and homogeneous surface with more regular aspects and equal particle sizes.

  9. 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.

  10. Orbital Period Investigations of Two W UMa-type Binaries: AH Aur and V728 Her

    NASA Astrophysics Data System (ADS)

    Yu, Yun-Xia; Xiang, Fu-Yuan; Hu, Ke

    2016-04-01

    The orbital period changes of two W UMa-type binaries, AH Aur and V728 Her, are investigated based on all available times of the light minimum taken from the databases and literature. It is revealed that the orbital period of AH Aur shows a long-term decrease at a rate of {dP}/{dt}=-2.491× {10}-7 days yr-1. For V728 Her, we find that the orbital period exhibits a secular increase at a rate of {dP}/{dt}=3.793× {10}-7 days yr-1. The secular period changes suggest that AH Aur and V728 Her are undergoing rapid mass transfer between the primary star and the secondary companion.

  11. Solution structure of the isolated histone H2A-H2B heterodimer.

    PubMed

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-Ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1-β1-α2-β2-α3-αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {(1)H}-(15)N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  12. Solution structure of the isolated histone H2A-H2B heterodimer

    PubMed Central

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1–β1–α2–β2–α3–αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {1H}-15N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27–34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  13. Ah-receptor controlled luciferase expression: A novel species-specific bioassay for Ah-receptor active compounds in environmental matrices

    SciTech Connect

    Murk, A.J.; Aarts, J.M.M.J.G.; Koeman, J.H.; Brouwer, A.; Denison, M.S.

    1995-12-31

    Polyhalogenated aromatic hydrocarbons (PHAHs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are persistent lipophilic compounds that accumulate especially in sediments and in top predators of the aquatic foodchain. PHAHs elicit a number of common toxic responses, which are highly species-specific. The most toxic, planar, PHAHs share a common mechanism of action mediated by the aryl hydrocarbon receptor (AhR). Based on this mechanism, the toxic equivalency factor (TEF) concept has been developed, allowing hazard and risk assessment for mixtures of PHAHs. The TEF-approach assumes additive responses, but also synergistic and antagonistic interactions have been observed. In addition, the often large number of compounds in a mixture, low levels of individual congeners, possible presence of unknown AhR-active substances, and species differences in inducibility, ask for an comprehensive approach in hazard assessment. A number of recombinant cell lines, including Hepa1c1c7 mouse and H411E rat hepatoma cell lines, were developed, showing AhR-mediated firefly (Photinuspyralis) luciferase gene expression. The response by 2,3,7,8-TCDD in the CALUX (chemical activated luciferase expression) assay with these cell lines is dose-dependent, and not subjected to substrate inhibition at higher ligand concentrations. The detection limit for 2,3,7,8-TCDD is below 1 pM (0.2 fmol). The luciferase assay has been successfully applied for monitoring the amount of AhR-active compounds in small aliquots of blood plasma and in both sediment and pore-water samples, of which examples will be presented.

  14. Functional and phenotypic effects of AhR activation in inflammatory dendritic cells

    SciTech Connect

    Bankoti, Jaishree; Rase, Ben; Simones, Tom; Shepherd, David M.

    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 were 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.

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

    PubMed Central

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

    2014-01-01

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

  16. Physical Parameters of the Overcontact Binary AH Cnc in the Old Open Cluster M 67

    NASA Astrophysics Data System (ADS)

    Yakut, K.; Aerts, C.

    2006-04-01

    We present a photometric study of the overcontact binary AH Cnc. The CCD observations were done with the Russian-Turkish 1.5 m telescope and the light-curve was solved with the Wilson-Devinney code. The physical parameters of the components have been deduced as M1 = 1.22 Msun, M2 = 0.20 Msun, R1 = 1.37 Rsun, R2 = 0.66 Rsun, L1 = 2.65 Lsun and L2 = 0.63 Lsun from the obtained orbital parameters and the distance modules of M 67. AH Cnc has been compared with similar systems in the Hertzsprung-Russell diagram.

  17. Gene cloning and expression analysis of AhR and CYP4 from Pinctada martensii after exposed to pyrene.

    PubMed

    Du, Junqiao; Liao, Chenghong; Zhou, Hailong; Diao, Xiaoping; Li, Yuhu; Zheng, Pengfei; Wang, Fuqiang

    2015-10-01

    Pyrene, a typical polycyclic aromatic hydrocarbon, is a common pollutant in the marine environment. Polycyclic aromatic hydrocarbons initiate cellular detoxification in an exposed organism via the activation of the aryl hydrocarbon receptor (AhR). Subsequent metabolism of these xenobiotics is mainly by the cytochrome P450 enzymes of the phase I detoxification system. Full-length complementary DNA sequences from the pearl oyster Pinctada martensii (pm) encoding AhR and cytochrome P4 were cloned. The P. martensii AhR complementary DNA sequence constitutes an open reading frame that encodes for 848 amino acids. Sequence analysis indicated PmAhR showed high similarity with its homologues of other bivalve species. The cytochrome P(CYP)4 complementary DNA sequence of P. martensii constitutes an open reading frame that encodes for 489 amino acids. Quantitative real-time analysis detected both PmAhR and PmCYP4 messenger RNA expressions in the mantle, gill, hepatapancreas and adductor muscle of P. martensii exposed to pyrene. The highest transcript-band intensities of PmAhR and PmCYP4 were observed in the gill. Temporal expression of PmAhR and PmCYP4 messenger RNAs induction was observed in gills and increased between 3 and 5 days post exposure; then returned to control level. These results suggest that messenger RNAs of PmAhR and PmCYP4 in pearl oysters might be useful parameters for monitoring marine environment pyrene pollution.

  18. Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production.

    PubMed

    Chiba, Takahito; Uchi, Hiroshi; Tsuji, Gaku; Gondo, Hisaki; Moroi, Yoichi; Furue, Masutaka

    2011-02-01

    The dioxins and dioxin-like compounds in cigarette smoke regulate various immunological responses via the arylhydrocarbon receptor (AhR). These environmental toxicants are known to cause bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have demonstrated that AhR activation upregulates the expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) in the airway epithelial cell line. However, the mechanism for the production of mucin has not been clarified. In this study, we investigated the role and pathway of AhR in airway epithelial cells by using selective agonists and antagonists. After stimulation with or without benzopyrene (B[a]P), an AhR agonist, MUC5AC expression was measured by real-time RT-PCR. The mechanism of AhR-induced MUC5AC expression in airway epithelial cells was studied in terms of the production of cytokine and reactive oxygen species (ROS). Treatment with B[a]P increased ROS generation in NCI-H₂₉₂ cells. Furthermore, B[a]P-induced MUC5AC upregulation and mucin production were inhibited by AhR siRNA or the use of an antioxidative agent. These results suggest that the AhR-induced increase of mucin production is partially mediated by ROS generation. An antioxidant therapy approach may help to cure AhR-induced mucus hypersecretory diseases. PMID:20709182

  19. Molecular and Chemical Analysis of the Lipopolysaccharide from Aeromonas hydrophila Strain AH-1 (Serotype O11)

    PubMed Central

    Merino, Susana; Canals, Rocío; Knirel, Yuriy A.; Tomás, Juan M.

    2015-01-01

    A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria strains isolated from humans and fish have been described; these strains classified to serotype O11 are serologically related by their lipopolysaccharide (LPS) O-antigen (O-polysaccharide), and the presence of an S-layer consisting of multiple copies of a crystalline surface array protein with a molecular weight of 52 kDa in the form of a crystalline surface array which lies peripheral to the cell wall. A. hydrophila strain AH-1 is one of them. We isolated the LPS from this strain and determined the structure of the O-polysaccharide, which was similar to that previously described for another strain of serotype O11. The genetics of the O11-antigen showed the genes (wbO11 cluster) in two sections separated by genes involved in biosynthesis and assembly of the S-layer. The O11-antigen LPS is an example of an ABC-2-transporter-dependent pathway for O-antigen heteropolysaccharide (disaccharide) assembly. The genes involved in the biosynthesis of the LPS core (waaO11 cluster) were also identified in three different chromosome regions being nearly identical to the ones described for A. hydrophila AH-3 (serotype O34). The genetic data and preliminary chemical analysis indicated that the LPS core for strain AH-1 is identical to the one for strain AH-3. PMID:25874921

  20. ATel 7477: Classification of PS15ahs as a Type Ia Supernova

    NASA Astrophysics Data System (ADS)

    Piascik, A. S.; Steele, I. A.

    2015-05-01

    We conducted a spectroscopic observation of transient PS15ahs (Atel #7471) at 2015-05-06T00:57:23 UT. One spectrum was obtained in the visible (400-800nm) with resolution R~350 using the SPRAT spectrograph on the Liverpool Telescope located at Roque de los Muchachos. ...

  1. 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

  2. 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

  3. RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro.

    PubMed Central

    Kretzschmar, M; Stelzer, G; Roeder, R G; Meisterernst, M

    1994-01-01

    We have isolated from a crude Hela cell cofactor fraction (USA) a novel positive cofactor that cooperates with the general transcription machinery to effect efficient stimulation of transcription by GAL4-AH, a derivative of the Saccharomyces cerevisiae regulatory factor GAL4. PC2 was shown to be a 500-kDa protein complex and to be functionally and biochemically distinct from native TFIID and previously identified cofactors. In the presence of native TFIID and other general factors, PC2 was necessary and sufficient for activation by GAL4-AH. Cofactor function was specific for transcriptional activation domains of GAL4-AH. The repressor histone H1 further potentiated but was not required for activation of transcription by GAL4-AH. On the basis of the observation that PC2 exerts entirely positive effects on transcription, we propose a model in which PC2 increases the activity of the preinitiation complex in the presence of an activator, thereby establishing a specific pathway during activation of RNA polymerase II. Images PMID:8196633

  4. AH-64 monocular HMD visual assessment during urban combat in operation Iraqi freedom (OIF)

    NASA Astrophysics Data System (ADS)

    Rash, Clarence E.; Heinecke, J. Kevin; Hiatt, Keith L.

    2007-04-01

    In the first two decades of the fielding of the monocular helmet-mounted display (HMD) flown in the U.S. Army's AH-64 Apache attack helicopter, a number of studies reported a significant incidence of physical visual symptoms and illusions. In 2004, a similar study looked at the presence of these complaints during the first combat phase of Operation Iraqi Freedom (OIF). The study found a general trend of a reduced frequency of complaints associated with the AH-64's HMD. A follow-up study has been conducted to validate this downward trend and to investigate the impact the shift in mission role of the AH-64 from one of open-field tank hunter to one of close-quarter urban combat. Thirty-eight AH-64D pilots were asked to complete a survey questionnaire that solicited data about the presence and frequency of the visual complaints reported in previous studies. Data for physical visual symptoms and static and dynamic illusions were found not to be significantly different from frequencies reported in the previous OIF study. Both OIF studies reported headache as the prominent physical complaint with height judgment and slope estimation as the most frequently reported static illusions and with undetected drift and faulty closure judgment as the two most frequently reported dynamic illusions.

  5. 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.

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

    PubMed

    Forn-Cuní, Gabriel; Tomás, Juan M; Merino, Susana

    2016-09-01

    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.

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

    PubMed

    Forn-Cuní, Gabriel; Tomás, Juan M; Merino, Susana

    2016-09-01

    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.

  8. 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…

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

    PubMed Central

    Hansen, Mette S.; Holm, Elisabeth; Hjulsager, Charlotte K.; Chriél, Mariann; Pedersen, Karl; Andresen, Lars O.; Abildstrøm, Morten; Jensen, Trine H.; Larsen, Lars E.

    2015-01-01

    Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June–August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined. PMID:25811098

  10. 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. PMID:24565026

  11. 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

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

    PubMed

    Forn-Cuní, Gabriel; Tomás, Juan M; Merino, Susana

    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

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

    PubMed

    Forn-Cuní, Gabriel; Tomás, Juan M; Merino, Susana

    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

  14. An in vitro rainbow trout cell bioassay for AhR-mediated toxins

    SciTech Connect

    Richter, C.A.; Giesy, J.P.; Denison, M.S.

    1995-12-31

    The toxicity of PCBs, dioxins, and other halogenated aromatic hydrocarbons (HAHS) at environmentally relevant concentrations is in large part mediated through the aromatic hydrocarbon receptor (AhR). Bioassays which measure the activity of genes regulated by the receptor provide an integrative measure of the total AhR-mediated toxicity of a sample. The authors have recently developed and characterized a bioassay using recombinant rainbow trout hepatoma cells containing the firefly luciferase reporter gene under the regulation of the AhR. The cell line is designated Remodulated Lightning Trout (RLT). The RLT bioassay is relevant to fish, and is useful as a rapid screening device, a guide for chemical analysis, and a tool for studies of the AhR mechanism. The responses of the RLT cell line to various PCB congeners are similar to responses of in vivo fish bioassays. The authors now report on the responses of the bioassay to dioxins, dibenzofurans, and other related compounds as compared to in vivo fish bioassays. The authors will also report on the utility of the RLT bioassay in measuring the total TEQ of complex mixtures.

  15. 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.

  16. Research Updates: Experimental Evaluation of 2009 Pandemic A/H1N1 in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March 2009, a novel pandemic A/H1N1 emerged in the human population in North America (2). The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before be...

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

    PubMed

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

    2014-11-01

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

  18. Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern China.

    PubMed

    Wu, Haibo; Peng, Xiaorong; Xu, Lihua; Jin, Changzhong; Cheng, Linfang; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2014-08-01

    Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans.

  19. 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.

  20. French Experience of 2009 A/H1N1v Influenza in Pregnant Women

    PubMed Central

    Dubar, Grégory; Azria, Elie; Tesnière, Antoine; Dupont, Hervé; Le Ray, Camille; Baugnon, Thomas; Matheron, Sophie; Luton, Dominique; Richard, Jean-Christophe; Launay, Odile; Tsatsaris, Vassilis; Goffinet, François; Mignon, Alexandre

    2010-01-01

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

  1. AH Cam: A metal-rich RR Lyrae star with the shortest known Blazhko period

    NASA Technical Reports Server (NTRS)

    Smith, Horace A.; Matthews, Jaymie M.; Lee, Kevin M.; Williams, Jeffrey; Silbermann, N. A.; Bolte, Michael

    1994-01-01

    Analysis of 746 new V-band observations of the RR Lyrae star AH Cam obtained during 1989 - 1992 clearly show that its light curve cannot be described by a single period. In fact, at first glance, the Fourier spectrum of the photometry resembles that of a double-mode pulsator, with peaks at a fundamental period of 0.3686 d and an apparent secondary period of 0.2628 d. Nevertheless, the dual-mode solution is a poor fit to the data. Rather, we believe that AH Cam is a single-mode RR Lyrae star undergoing the Blazhko effect: periodic modulation of the amplitude and shape of its light curve. What was originally taken to be the period of the second mode is instead the 1-cycle/d alias of a modulation sidelobe in the Fourier spectrum. The data are well described by a modulation period of just under 11 d, which is the shortest Blazhko period reported to date in the literature and confirms the earlier suggestion by Goranskii. A low-resolution spectrum of AH Cam indicates that it is relatively metal rich, with delta-S less than or = 2. Its high metallicity and short modulation period may provide a critical test of at least one theory for the Blazhko effect. Moskalik's internal resonance model makes specific predictions of the growth rate of the fundamental model vs fundamental period. AH Cam falls outside the regime of other known Blazhko variables and resonance model predictions, but these are appropriate for metal-poor RR Lyrae stars. If the theory matches the behavior of AH Cam for a metal-rich stellar model, this would bolster the resonance hypothesis.

  2. 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

    2010-05-01

    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.

  3. 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.

  4. The immune phenotype of AhR null mouse mutants: not a simple mirror of xenobiotic receptor over-activation.

    PubMed

    Esser, Charlotte

    2009-02-15

    Intrinsic and induced cell differentiation and the cellular response to endogenous and exogenous signals are hallmarks of the immune system. Specific and common signalling cascades ensure a highly flexible and adapted response. Increasing evidence suggests that gene modulation by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is an important part of these processes. For decades the AhR has been studied mainly for its toxic effects after artificial activation by man-made chemical pollutants such as dioxins. These studies gave important, albeit to some extent skewed, evidence for a mechanistic link between the AhR and the immune system. AhR null mutants and other mutants of the AhR signalling pathway have been generated and used to analyse the physiological function of the AhR, including for the developing and antigen-responding immune system. In this review I look at the natural immunological function(s) of the AhR.

  5. 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.

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

    PubMed

    Sun, Yang; Lu, Hongzhou

    2014-04-01

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

  7. Influenza A(H1N1)pdm09 virus in pigs, Togo, 2013

    PubMed Central

    Ducatez, Mariette F.; Awoume, Félix; Webby, Richard J.

    2015-01-01

    We collected 325 nasal swabs from freshly slaughtered previously healthy pigs from October 2012 through January 2014 in a slaughterhouse near Lomé in Togo. Influenza A virus genome was detected by RT-PCR in 2.5% to 12.3% of the pooled samples, and results of hemagglutinin subtyping RT-PCR assays showed the virus in all the positive pools to be A(H1N1)pdm09. Virus was isolated on MDCK cells from a representative specimen, A/swine/Togo/ONA32/2013(H1N1). The isolate was fully sequenced and harbored 8 genes similar to A(H1N1)pdm09 virus genes circulating in humans in 2012–2013, suggesting human-to-swine transmission of the pathogen. PMID:25778544

  8. Schedules of Controlled Substances: Placement of AH-7921 Into Schedule I. Final order.

    PubMed

    2016-04-14

    With the issuance of this final order, the Administrator of the Drug Enforcement Administration places the substance AH-7921 (Systematic IUPAC Name: 3,4-dichloro-N-[(1dimethylamino)cyclohexylmethyl]benzamide), including its isomers, esters, ethers, salts, and salts of isomers, esters and ethers, into schedule I of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act and is required in order for the United States to discharge its obligations under the Single Convention on Narcotic Drugs, 1961. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, import, export, engage in research or conduct instructional activities with, or possess), or propose to handle, AH-7921. PMID:27101639

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

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaoxiang; Zhuang, Huisheng

    2010-11-01

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

  10. Precursor systems analyses of automated highway systems. AHS roadway analysis: Final report. Volume 3. Report for 9 September 1993-30 October 1994

    SciTech Connect

    Elias, J.A.

    1995-05-01

    The programs described by this eight-volume report, a resource materials document type, identified the issues and risks associated with the potential design, development, and operation of an Automated Highway System (AHS), a highway system that utilizes limited access roadways and provides `hands off` driving. The 17 task reports (A through P plus Representative Systems Configurations) are organized into 8 volumes. This volume, which describes roadway analyses, covers four tasks in three chapters. Urban and Rural AHS Analysis (Task A). AHS Roadway Deployment Analysis (Task H), Impact of Non-AHS Roads (Task I), AHS Roadway Operation Analysis (Task K).

  11. 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. PMID:26038499

  12. Cellular responses to oxidative stress: The (Ah) gene battery as a paradigm

    SciTech Connect

    Nebert, D.W.; Petersen, D.D.; Fornace, A.J. Jr. )

    1990-08-01

    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 the authors 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. The radiation deletion homozygote c{sup 14CoS}/c{sup 14CoS} mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c{sup 14CoS}/c{sup 14CoS} 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 c{sup 14Cos}/c{sup 14CoS} mouse contains a gene(s), which they 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 c{sup 14CoS}/c{sup 14CoS} 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.

  13. Equine Influenza A(H3N8) Virus Isolated from Bactrian Camel, Mongolia

    PubMed Central

    Yondon, Myagmarsukh; Zayat, Batsukh; Nelson, Martha I.; Heil, Gary L.; Anderson, Benjamin D.; Lin, Xudong; Halpin, Rebecca A.; McKenzie, Pamela P.; White, Sarah K.; Wentworth, David E.

    2014-01-01

    Because little is known about the ecology of influenza viruses in camels, 460 nasal swab specimens were collected from healthy (no overt illness) Bactrian camels in Mongolia during 2012. One specimen was positive for influenza A virus (A/camel/Mongolia/335/2012[H3N8]), which is phylogenetically related to equine influenza A(H3N8) viruses and probably represents natural horse-to-camel transmission. PMID:25418532

  14. 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

  15. Relationship between Ah receptor-mediated polychlorinated biphenyl (PCB)-induced humoral immunosuppression and thymic atrophy.

    PubMed

    Silkworth, J B; Antrim, L

    1985-12-01

    Thymic atrophy and humoral immunosuppression by certain polychlorinated biphenyls is associated with the aromatic hydrocarbon (Ah) receptor in mice. We examined the relationship between these two toxic effects. 3,3',4,4'-Tetrachlorobiphenyl (TCB), which causes immunosuppression and thymic atrophy, and 2,3,3',4,4',5-hexachlorobiphenyl, which causes immunosuppression without thymic atrophy, were administered i.p. to C57BL/6 mice at 0, 35 and 350 mumol/kg b.wt. 2 days before i.v. immunization with 10 micrograms of Escherichia coli lipopolysaccharide. Both congeners caused significant suppression of the day 4 anti-lipopolysaccharide plaque-forming cell response/spleen (less than or equal to 46% of control). TCB (350 mumol/kg) was also administered 2 days before either a primary or secondary i.p. immunization with sheep erythrocytes. TCB treatment before primary immunization had no effects on the day 5 secondary response, whereas treatment before the secondary immunization significantly inhibited both day 5 immunoglobulin M and immunoglobulin G plaque-forming cells (less than 10 and less than 2% of control, respectively) and decreased serum antibody. TCB administered either 8 or 2 days before or 2 or 4 days after immunization with sheep erythrocytes demonstrated that significant suppression of both plaque-forming cells and serum antibody could occur without thymic atrophy. Immunity was most impaired when TCB was given 2 days before immunization. These results demonstrate that thymic atrophy does not always accompany the severe immunosuppression caused by Ah receptor ligands and suggests that it may not be a sensitive measure of Ah receptor-mediated immunosuppression. The data also suggests that differentiation of B lymphocytes into antibody producing cells is impaired during Ah receptor-mediated gene activation.

  16. 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.

  17. 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. PMID:26306756

  18. 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

  19. 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.

  20. Sinulolides A-H, new cyclopentenone and butenolide derivatives from soft coral Sinularia sp.

    PubMed

    Yang, Bin; Wei, Xiaoyi; Huang, Jingxia; Lin, Xiuping; Liu, Juan; Liao, Shengrong; Wang, Junfeng; Zhou, Xuefeng; Wang, Lishu; Liu, Yonghong

    2014-10-01

    Eight new compounds, sinulolides A-H (1-8), along with two known compounds, α-methoxy-2,3-dimethyl-butenolide (9) and sinularone D (10), were isolated from the soft coral Sinularia sp. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations were determined on the basis of electronic circular dichroism (ECD) data analysis. Compounds 5 and 10 exhibited moderate effects for the inhibition of NF-κB activation.

  1. Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining.

    PubMed

    Manabe, Shun; Hatano, Michiyasu; Yazaki, Masahide; Nitta, Kosaku; Nagata, Michio

    2015-12-01

    AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.

  2. 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.

  3. 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. PMID:26829383

  4. Long life 80Ah standard IPV NiH2 battery cell

    NASA Astrophysics Data System (ADS)

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

    1995-02-01

    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.

  5. Human Antibody Responses to Avian Influenza A(H7N9) Virus, 2013

    PubMed Central

    Guo, Li; Zhang, Xi; Ren, Lili; Yu, Xuelian; Chen, Lijuan; Zhou, Hongli; Gao, Xin; Teng, Zheng; Li, Jianguo; Hu, Jiayu; Wu, Chao; Xiao, Xia; Zhu, Yiyi; Wang, Quanyi; Pang, Xinghuo; Jin, Qi; Wu, Fan

    2014-01-01

    Understanding host antibody response is crucial for predicting disease severity and for vaccine development. We investigated antibody responses against influenza A(H7N9) virus in 48 serum samples from 21 patients, including paired samples from 15 patients. IgG against subtype H7 and neutralizing antibodies (NAbs) were not detected in acute-phase samples, but ELISA geometric mean titers increased in convalescent-phase samples; NAb titers were 20–80 (geometric mean titer 40). Avidity to IgG against subtype H7 was significantly lower than that against H1 and H3. IgG against H3 was boosted after infection with influenza A(H7N9) virus, and its level in acute-phase samples correlated with that against H7 in convalescent-phase samples. A correlation was also found between hemagglutinin inhibition and NAb titers and between hemagglutinin inhibition and IgG titers against H7. Because of the relatively weak protective antibody response to influenza A(H7N9), multiple vaccinations might be needed to achieve protective immunity. PMID:24447423

  6. 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.

  7. Physicochemical Properties and Surfaces Morphologies Evaluation of MTA FillApex and AH Plus

    PubMed Central

    Borges, Álvaro Henrique; Orçati Dorileo, Maura Cristiane Gonçales; Villa, Ricardo Dalla; Borba, Alexandre Meireles; Semenoff, Tereza Aparecida Delle Vedove; Guedes, Orlando Aguirre; Estrela, Cyntia Rodrigues Araújo; Bandeca, Matheus Coelho

    2014-01-01

    The solubility, pH, electrical conductivity, and radiopacity of AH Plus and MTA FillApex were evaluated. In addition, the surfaces morphologies of the sealers were analyzed by using scanning electron microscopy. For pH test, the samples were immersed in distilled water at different periods of time. The same solution was used for electrical conductivity measurement. The solubility and radiopacity were evaluated according to ANSI/ADA. Statistical analyses were carried out at 5% level of significance. MTA FillApex presented higher mean value for solubility and electrical conductivity. No significant difference was observed in the mean values for pH reading. AH Plus presented higher radiopacity mean values. MTA FillApex presented an external surface with porosities and a wide range of sizes. In conclusion, the materials fulfill the ANSI/ADA requirements when considering the radiopacity and solubility. AH Plus revealed a compact and homogeneous surface with more regular aspects and equal particle sizes. PMID:24883413

  8. A generalized dynamic balancing procedure for the AH-64 tail rotor

    NASA Astrophysics Data System (ADS)

    Kunz, Donald L.; Newkirk, Mark C.

    2009-09-01

    The tail rotors on the AH-64A Apache and AH-64D Longbow Apache incorporate a unique design, which includes two, two-bladed teetering rotors that have an azimuth spacing of 55°, instead of the more usual 90°. Maintainers have observed that some Apache tail rotors can be extraordinarily difficult to balance dynamically. This investigation uses RCAS (Rotorcraft Comprehensive Analysis System) numerical simulations of tail rotor response when mass is added to the tips of single and adjacent blades to investigate possible causes for this balancing difficulty. The simulations show that the 1/rev, vertical, vibratory force response due to added tip mass varies as a function of the mass distribution between two adjacent blades, and the azimuth spacing between the two blades. As a result, the tail rotor balance sensitivity coefficients, if used as for a single blade, will be inaccurate; and may be a prime contributor to the problems observed while balancing tail rotors. An analytical model of the AH-64D tail rotor, with characteristics similar to the RCAS model, and which incorporates the influence of structural impedance through the balance sensitivity coefficients and phase angles, is used to develop a method for accurately determining the amount of tip mass required to reduce the 1/rev vibrations to acceptable levels.

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

    PubMed Central

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

    2016-01-01

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

  10. Examination of design options for 35 Ah ambient temperature Li-TiS sub 2 cells

    NASA Technical Reports Server (NTRS)

    Shen, D. H.; Rao, S. S.; Yen, S. P. S.; Somoano, R. B.

    1986-01-01

    The Jet Propulsion Laboratory is actively engaged in the development of ambient temperature rechargable lithium cells for future NASA geosynchronous Earth orbit (GEO) missions. To achieve these ambitious goals, Li-TiS2, Li-MoS3, and Li-V6O13 systems were examined in detail. Among these three, the Li-TiS2 system has shown the longest life cycle and highest rate capability. Experimental Li-TiS2 batteries (10.5 V, 0.4 Ah) developed in-house have completed eight simulated and accelerated GEO seasons successfully. Inview of the encouraging results, the design options were examined for a scaled-up Li-TiS2 cell. It is hoped that the results of these studies will provide guidelines for prioritizing the research efforts and guiding the selection of optimized materials. Designs for 35 Ah Li-TiS2 cell were examined because present day geosynchronous satellites are powered by batteries of 35 Ah capacity. A computer program was developed to evaluate the influence of various design parameters on the specific energy and the rate capability of the cells.

  11. A Newly Emerged Swine-Origin Influenza A(H3N2) Variant Dampens Host Antiviral Immunity but Induces Potent Inflammasome Activation.

    PubMed

    Cao, Weiping; Mishina, Margarita; Ranjan, Priya; De La Cruz, Juan A; Kim, Jin Hyang; Garten, Rebecca; Kumar, Amrita; García-Sastre, Adolfo; Katz, Jacqueline M; Gangappa, Shivaprakash; Sambhara, Suryaprakash

    2015-12-15

    We compared the innate immune response to a newly emerged swine-origin influenza A(H3N2) variant containing the M gene from 2009 pandemic influenza A(H1N1), termed "A(H3N2)vpM," to the immune responses to the 2010 swine-origin influenza A(H3N2) variant and seasonal influenza A(H3N2). Our results demonstrated that A(H3N2)vpM-induced myeloid dendritic cells secreted significantly lower levels of type I interferon (IFN) but produced significantly higher levels of proinflammatory cytokines and induced potent inflammasome activation. The reduction in antiviral immunity with increased inflammatory responses upon A(H3N2)vpM infection suggest that these viruses have the potential for increased disease severity in susceptible hosts. PMID:26068782

  12. HealthLines: Quick Tips for Seasonal Health, Safety and Fun... "Ah, when the sun beats down…"

    MedlinePlus

    ... Photo courtesy of Vitality Communications "Ah, when the sun beats down …" The National Cancer Institute estimates there ... prevent skin cancer is to guard against the sun. For children, it's especially important from an early ...

  13. 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

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

    PubMed Central

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

    2012-01-01

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

  15. Activation of A-H bonds (A = B, C, N, O, Si) by using monovalent phosphorus complexes [RP→M].

    PubMed

    Mathey, Francois; Duan, Zheng

    2016-02-01

    The available data on the activation of A-H sigma bonds by electrophilic terminal phosphinidene complexes are reviewed. Theoretical computations allow us to rationalize the experimental results. It appears that a successful insertion needs an initial interaction between the phosphinidene and the A-H bond, such as a donor-acceptor complex with a lone pair, a Coulombic interaction due to a negative charge on A or H, or a proximity effect.

  16. Experimental study of the efficiency of oxidized dextran for prevention of influenza A/H5N1.

    PubMed

    Shkurupy, V A; Potapova, O V; Sharkova, T V; Troitskii, A V; Gulyaeva, E P; Bystrova, T N; Shestopalov, A M

    2014-11-01

    Oxidized dextran is suggested for prevention of infection induced by influenza A/H5N1 viruses, methods of its use and doses are determined. Two intravenous injections of dextran 3 and 1 days before experimental infection of outbred mice by influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus resulted in a high preventive dose-dependent effect: the mean lifespan was 25% prolonged, the mortality decreased 3-fold. PMID:25403410

  17. 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

  18. Oseltamivir-Resistant Influenza A(H1N1)pdm09 Viruses, United States, 2013–14

    PubMed Central

    Okomo-Adhiambo, Margaret; Fry, Alicia M.; Su, Su; Nguyen, Ha T.; Elal, Anwar Abd; Negron, Elizabeth; Hand, Julie; Garten, Rebecca J.; Barnes, John; Xiyan, Xu; Villanueva, Julie M.

    2015-01-01

    We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013–14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance–conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses. PMID:25532050

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

    PubMed

    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.

  20. Myelinated Ah-type trigeminal ganglion neurons in female rats: neuroexcitability, chemosensitivity to histamine, and potential clinical impact.

    PubMed

    Liu, Hua; Xin, Ting; He, Wei; Li, Fang; Su, Zhi-Qiang

    2014-05-01

    Migraine is a chronic neurological disorder characterized by recurrent moderate-to-severe headaches often associated with numerous autonomic nervous system symptoms, and it is more prevalent in women. To fully understand the underlying mechanism, standard electrophysiology was performed with trigeminal ganglion neurons (TGNs) isolated from adult rats of both genders using the whole-cell patch clamp technique to test the distribution, neuroexcitability, and chemosensitivity to histamine. In addition to traditionally classified A- and C-type TGNs, myelinated Ah-type TGNs were also observed in females. The electrophysiological features showed low firing threshold and the capability to fire repetitively upon stimulation. Ah-type neurons also functionally expressed persistent TTX-R Na(+) channels with more hyperpolarized activating voltage. Iberiotoxin and NS11021 significantly altered the discharge profiles of Ah-type TGNs. Finally, Ah-type TGNs showed a more potent reaction to histamine, with relatively larger inward currents and membrane depolarization compared with C-types. These data provide evidence of the gender-specific distribution of myelinated Ah-type TGNs in adult female rats, characterized by a low threshold and high frequency of firing that are at least partially attributable to persistent TTX-R Na(+) and BK-KCa channel expression and potent chemosensitivity to histamine, suggesting that Ah-type TGNs may play a key role in gender differences in migraine. PMID:24686179

  1. Myelinated Ah-type trigeminal ganglion neurons in female rats: neuroexcitability, chemosensitivity to histamine, and potential clinical impact.

    PubMed

    Liu, Hua; Xin, Ting; He, Wei; Li, Fang; Su, Zhi-Qiang

    2014-05-01

    Migraine is a chronic neurological disorder characterized by recurrent moderate-to-severe headaches often associated with numerous autonomic nervous system symptoms, and it is more prevalent in women. To fully understand the underlying mechanism, standard electrophysiology was performed with trigeminal ganglion neurons (TGNs) isolated from adult rats of both genders using the whole-cell patch clamp technique to test the distribution, neuroexcitability, and chemosensitivity to histamine. In addition to traditionally classified A- and C-type TGNs, myelinated Ah-type TGNs were also observed in females. The electrophysiological features showed low firing threshold and the capability to fire repetitively upon stimulation. Ah-type neurons also functionally expressed persistent TTX-R Na(+) channels with more hyperpolarized activating voltage. Iberiotoxin and NS11021 significantly altered the discharge profiles of Ah-type TGNs. Finally, Ah-type TGNs showed a more potent reaction to histamine, with relatively larger inward currents and membrane depolarization compared with C-types. These data provide evidence of the gender-specific distribution of myelinated Ah-type TGNs in adult female rats, characterized by a low threshold and high frequency of firing that are at least partially attributable to persistent TTX-R Na(+) and BK-KCa channel expression and potent chemosensitivity to histamine, suggesting that Ah-type TGNs may play a key role in gender differences in migraine.

  2. 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

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

    PubMed

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

    2014-07-15

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

  4. 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

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

    PubMed

    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

  6. 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.

  7. Agonistic effect of selected isoflavones on arylhydrocarbon receptor in a novel AZ-AhR transgenic gene reporter human cell line.

    PubMed

    Bialesova, Lucia; Novotna, Aneta; Macejova, Dana; Brtko, Julius; Dvorak, Zdenek

    2015-07-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that controls the expression of a diverse set of genes. Structurally diverse compounds bind to AhR and act as AhR agonists. Well characterised family of natural AhR ligands are isoflavones, which are compounds found predominantly in soy beans or red clover. In this study we have examined agonistic effect of selected isoflavones (genistein, daidzein, biochanin A, formononetin and equol) on AhR in the novel transgenic gene reporter human cell line AZ-AhR, a stably transfected AhR-responsive cell line allowing rapid and sensitive assessment of AhR transcriptional activity. We demonstrated that biochanin A, formononetin and genistein at concentration 10(-4) mol/l exerted agonistic effects on AhR with fold activation of 309- fold, 108-fold and 27-fold, which is about 84.8%, 29.6% and 7.4%, respectively, of the value attained by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Daidzein and equol did not show any significant effects on AhR. PMID:25926549

  8. An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

    PubMed Central

    Aguilar-Yáñez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio A.; López-Pacheco, Felipe; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Lara-Mayorga, Itzel M.; Webb-Vargas, Yenny; León-Angel, Felipe O.; Rivero-Aranda, Ramón E.; Oropeza-Almazán, Yuriana; Ruiz-Palacios, Guillermo M.; Zertuche-Guerra, Manuel I.; DuBois, Rebecca M.; White, Stephen W.; Schultz-Cherry, Stacey; Russell, Charles J.; Alvarez, Mario M.

    2010-01-01

    Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings We expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. PMID:20661476

  9. Photometric solution and period analysis of the contact binary system AH Cnc

    NASA Astrophysics Data System (ADS)

    Peng, Ying-Jiang; Luo, Zhi-Quan; Zhang, Xiao-Bin; Deng, Li-Cai; Wang, Kun; Tian, Jian-Feng; Yan, Zheng-Zhou; Pan, Yang; Fang, Wei-Jing; Feng, Zhong-Wen; Tang, De-Lin; Liu, Qi-Li; Sun, Jin-Jiang; Zhou, Qiang

    2016-10-01

    Photometric observations of AH Cnc, a W UMa-type system in the open cluster M67, were carried out by using the 50BiN telescope. About 100 h of time-series B- and V -band data were taken, based on which eight new times of light minima were determined. By applying the Wilson-Devinney method, the light curves were modeled and a revised photometric solution of the binary system was derived. We confirmed that AH Cnc is a deep contact (f = 51%), low mass-ratio (q = 0.156) system. Adopting the distance modulus derived from study of the host cluster, we have re-calculated the physical parameters of the binary system, namely the masses and radii. The masses and radii of the two components were estimated to be respectively 1.188(±0.061) M ⊙, 1.332(±0.063) R ⊙ for the primary component and 0.185(±0.032) M ⊙, 0.592(±0.051) R ⊙ for the secondary. By adding the newly derived minimum timings to all the available data, the period variations of AH Cnc were studied. This shows that the orbital period of the binary is continuously increasing at a rate of dp/dt = 4.29 × 10‑10 d yr‑1. In addition to the long-term period increase, a cyclic variation with a period of 35.26 yr was determined, which could be attributed to an unresolved tertiary component of the system.

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

    PubMed Central

    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

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:27486858

  11. Ah Receptor–Mediated Suppression of Liver Regeneration through NC-XRE–Driven p21Cip1 Expression

    PubMed Central

    Jackson, Daniel P.; Li, Hui; Mitchell, Kristen A.; Joshi, Aditya D.

    2014-01-01

    Previous studies in hepatocyte-derived cell lines and the whole liver established that the aryl hydrocarbon receptor (AhR) can disrupt G1-phase cell cycle progression following exposure to persistent AhR agonists, such as TCDD (dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin). Growth arrest was attributed to inhibition of G1-phase cyclin-dependent kinase 2 (CDK2) activity. The present study examined the effect of TCDD exposure on liver regeneration following 70% partial hepatectomy in mice lacking the Cip/Kip inhibitors p21Cip1 or p27Kip1 responsible for regulating CDK2 activity. Assessment of the regenerative process in wild-type, p21Cip1 knockout, and p27Kip1 knockout mice confirmed that TCDD-induced inhibition of liver regeneration is entirely dependent on p21Cip1 expression. Compared with wild-type mice, the absence of p21Cip1 expression completely abrogated the TCDD inhibition, and accelerated hepatocyte progression through G1 phase during the regenerative process. Analysis of the transcriptional response determined that increased p21Cip1 expression during liver regeneration involved an AhR-dependent mechanism. Chromatin immunoprecipitation studies revealed that p21Cip1 induction required AhR binding to the newly characterized nonconsensus xenobiotic response element, in conjunction with the tumor suppressor protein Kruppel-like factor 6 functioning as an AhR binding partner. The evidence also suggests that AhR functionality following partial hepatectomy is dependent on a p21Cip1-regulated signaling process, intimately linking AhR biology to the G1-phase cell cycle program. PMID:24431146

  12. 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. PMID:23648424

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

    PubMed Central

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

    2011-01-01

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

  14. A highly immunogenic vaccine against A/H7N9 influenza virus.

    PubMed

    Cao, Weiping; Liepkalns, Justine S; Hassan, Ahmed O; Kamal, Ram P; Hofstetter, Amelia R; Amoah, Samuel; Kim, Jin Hyang; Reber, Adrian J; Stevens, James; Katz, Jacqueline M; Gangappa, Shivaprakash; York, Ian A; Mittal, Suresh K; Sambhara, Suryaprakash

    2016-02-01

    Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/H7N9 viral challenge suggesting its potential utility as a pandemic vaccine.

  15. EM experiments for computational model validation for AH-1S Cobra Helicopter

    SciTech Connect

    Nelson, S.D.

    1997-04-06

    The effort described here describes a set of outdoor experiments performed on the AH-1S Cobra helicopter in order to validate and compare to the computational electromagnetic models of the bulk structure of the airframe in the frequency bands up to 4 GHz. Also included in this were coupling measurements to wires and cables inside of the airframe and various cavity to HPM pulse in this frequency range as part of other activities. Additionally, the low power modeling compression will be completed in this time frame.

  16. Analysis of environmental issues for nursing aboard the USNS Mercy (T-AH 19).

    PubMed

    McKenzie, R T; Boren, D M

    2001-06-01

    The USNS Mercy (T-AH 19) is a unique environment for its staff and patients. Several environmental influences distinctively affect health, medical, and nursing care. Six main areas of environmental concern for operational nursing were examined. The strengths, weaknesses, opportunities, and threats to the internal environment of a hospital ship were explored. Findings indicate that the USNS Mercy meets or exceeds many environmental standards. However, there is significant room for improvement and nursing involvement in issues related to the management of infectious diseases, patient transport, care of patients with nuclear, biological, or chemical agents, and management of wastes aboard the ship. Nursing implications for research and practice are proposed.

  17. Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection

    PubMed Central

    Qin, Ying; Horby, Peter W.; Tsang, Tim K.; Chen, Enfu; Gao, Lidong; Ou, Jianming; Nguyen, Tran Hien; Duong, Tran Nhu; Gasimov, Viktor; Feng, Luzhao; Wu, Peng; Jiang, Hui; Ren, Xiang; Peng, Zhibin; Li, Sa; Li, Ming; Zheng, Jiandong; Liu, Shelan; Hu, Shixiong; Hong, Rongtao; Farrar, Jeremy J.; Leung, Gabriel M.; Gao, George F.; Cowling, Benjamin J.; Yu, Hongjie

    2015-01-01

    Background. The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. Methods. We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). Results. We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). Conclusions. The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1. PMID:25940354

  18. A comparison of apical sealing ability between GuttaFlow and AH plus: An in vitro study

    PubMed Central

    Patil, Prajakta; Rathore, Vishnu P. S.; Hotkar, Chetan; Savgave, Snehal S.; Raghavendra, K.; Ingale, Priya

    2016-01-01

    Aims: The present study aimed to compare apical sealing ability between GuttaFlow and AH Plus. Materials and Method: Eighty extracted human maxillary anterior teeth with fully formed apex and straight root were collected for this study. The root canals were cleaned and shaped using a standard step back preparation to size 60# master apical file at the established working length and divided into four groups: Group 1, GuttaFlow sealer with gutta-percha; Group 2, AH Plus sealer with gutta-percha; Group 3, positive control group (Teeth were instrumented and left without obturation); Group 4, negative control group (Teeth were totally coated with nail varnish) Dye leakage was carried out. Statistical analysis was done using the Statistical Package for the Social Sciences software and Student's unpaired t-test. Results: The GuttaFlow group had a mean leakage of 1.38 mm whereas AH Plus had a mean of 1.425 mm. The standard deviation of GuttaFlow and AH Plus were 0.3861 and 0.3226, respectively. Student's unpaired t-test disclosed no significant difference (P < 0.05) between the groups. Conclusion: None of the sealers used in the study could completely seal the apical foramen to have a fluid-tight seal. GuttaFlow and AH Plus showed no statistically significant difference in microleakage; the better result was shown by GuttaFlow. PMID:27583228

  19. FACT disrupts nucleosome structure by binding H2A-H2B with conserved peptide motifs

    PubMed Central

    Kemble, David J.; McCullough, Laura L.; Whitby, Frank G.; Formosa, Tim; Hill, Christopher P.

    2015-01-01

    SUMMARY FACT, a heterodimer of Spt16 and Pob3, is an essential histone chaperone. We show that the H2A-H2B binding activity that is central to FACT function resides in short acidic regions near the C-termini of each subunit. Mutations throughout these regions impact binding and cause correlated phenotypes that range from mild to lethal, with the largest individual contributions unexpectedly coming from an aromatic residue and a nearby carboxylate residue within each domain. Spt16 and Pob3 bind overlapping sites on H2A-H2B, and Spt16-Pob3 heterodimers simultaneously bind two H2A-H2B dimers, the same stoichiometry as the components of a nucleosome. An Spt16:H2A-H2B crystal structure explains the biochemical and genetic data, provides a model for Pob3 binding, and implies a mechanism for FACT reorganization that we confirm biochemically. Moreover, unexpected similarity to binding of ANP32E and Swr1 with H2A.Z-H2B reveals that diverse H2A-H2B chaperones use common mechanisms of histone binding and regulating nucleosome functions. PMID:26455391

  20. Impact of influenza A(H1N1)pdm09 virus on circulation dynamics of seasonal influenza strains in Kenya.

    PubMed

    Majanja, Janet; Njoroge, Rose N; Achilla, Rachel; Wurapa, Eyako K; Wadegu, Meshack; Mukunzi, Silvanos; Mwangi, Josephat; Njiri, James; Gachara, George; Bulimo, Wallace

    2013-05-01

    We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008-July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription-polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya.

  1. The pandemic potential of avian influenza A(H7N9) virus: a review.

    PubMed

    Tanner, W D; Toth, D J A; Gundlapalli, A V

    2015-12-01

    In March 2013 the first cases of human avian influenza A(H7N9) were reported to the World Health Organization. Since that time, over 650 cases have been reported. Infections are associated with considerable morbidity and mortality, particularly within certain demographic groups. This rapid increase in cases over a brief time period is alarming and has raised concerns about the pandemic potential of the H7N9 virus. Three major factors influence the pandemic potential of an influenza virus: (1) its ability to cause human disease, (2) the immunity of the population to the virus, and (3) the transmission potential of the virus. This paper reviews what is currently known about each of these factors with respect to avian influenza A(H7N9). Currently, sustained human-to-human transmission of H7N9 has not been reported; however, population immunity to the virus is considered very low, and the virus has significant ability to cause human disease. Several statistical and geographical modelling studies have estimated and predicted the spread of the H7N9 virus in humans and avian species, and some have identified potential risk factors associated with disease transmission. Additionally, assessment tools have been developed to evaluate the pandemic potential of H7N9 and other influenza viruses. These tools could also hypothetically be used to monitor changes in the pandemic potential of a particular virus over time.

  2. Antibacterial Activity of MTA Fillapex and AH 26 Root Canal Sealers at Different Time Intervals

    PubMed Central

    Jafari, Farnaz; Samadi Kafil, Hossein; Jafari, Sanaz; Aghazadeh, Mohammad; Momeni, Tahereh

    2016-01-01

    Introduction: The main goal of endodontic treatment is elimination of bacteria and their by-products from infected root canals. This study compared the antibacterial effect of two different sealers, AH 26 and MTA Fillapex, on 4 microorganisms 24, 48 and 72 h and 7 days after mixing. Methods and Materials: The microorganisms used in this study consisted of Lactobacillus acidophilus (ATCC 4356), Lactobacillus casei (ATCC 39392), Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212). This test is based on the growth of bacteria and turbidity measurement technique using a spectrophotometer, and direct contact was conducted. Multiple comparisons were carried out using repeated-measures ANOVA followed by Tukey’s test and student’s t-test. The level of significance was set at 0.05. Results: The antibacterial activity in the indirect technique was more than the technique with both sealers. In the direct technique the antibacterial activity on all microorganisms were lower for MTA Fillapex sealer. In the indirect technique, both sealers exhibited similar antibacterial properties. Conclusion: The antibacterial effect of MTA Fillapex sealer was significantly less than that of AH 26 sealer in the direct technique. The antibacterial effects of both sealers were similar in the indirect technique. PMID:27471530

  3. Behavioural response in educated young adults towards influenza A(H1N1)pdm09.

    PubMed

    Chen, S C; Hsieh, N H; You, S H; Wang, C H; Liao, C M

    2015-07-01

    The purpose of this paper was to determine how contact behaviour change influences the indoor transmission of influenza A(H1N1)pdm09 among school children. We incorporated transmission rate matrices constructed from questionnaire responses into an epidemiological model to simulate contact behaviour change during an influenza epidemic. We constructed a dose-response model describing the relationships between contact rate, viral load, and respiratory symptom scores using published experimental human infection data for A(H1N1)pdm09. Findings showed that that mean numbers of contacts were 5.66 ± 6.23 and 1.96 ± 2.76 d-1 in the 13-19 and 40-59 years age groups, respectively. We found that the basic reproduction number (R 0) was <1 during weekends in pandemic periods, implying that school closures or class suspensions are probably an effective social distancing policy to control pandemic influenza transmission. We conclude that human contact behaviour change is a potentially influential factor on influenza infection rates. For substantiation of this effect, we recommend a future study with more comprehensive control measures.

  4. 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.

  5. 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.

  6. Structural Integrity Recording System (SIR) for U.S. Army AH-1G Helicopters

    NASA Astrophysics Data System (ADS)

    Farrell, T. G.; Johnson, R. B.; Tyler, M. C.

    1981-03-01

    A Structural Integrity Recording System (SIRS) was designed and developed to track the fatigue damage accumulation on 10 critical helicopter components for the subsequent timely replacement of such components for safer and more economical helicopter operation. SIRS comprises three discrete but interrelated subsystems: an airborne microprocessor-based recorder, a portable flight-line data retrieval unit, and a software system. The validation of SIRS, initially configured for the AH-1G helicopter, consisted of two phases. Phase I (Development Test and Evaluation - DT E) covered the design, fabrication, laboratory qualification testing, reliability analysis, and flight-testing of the prototype SIRS recorder. Phase II (Initial Operational Test and Evaluation - IOT E) covered the evaluation of the entire system operation and the resultant data acquired during a 3-month recording period with five AH-1G's, each equipped with a SIRS recorder. As the documentation of both DT E and IOT E, this report describes the characteristics and functions of the entire system and details the successful performance of the SIRS recorder in the laboratory qualification testing and the flight environment. The SIRS recorder performed as designed, operated reliably, and yielded valid data.

  7. 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.

  8. AH-64 aviator impressions of IHADSS HMD flight in Operation Iraqi Freedom

    NASA Astrophysics Data System (ADS)

    Hiatt, Keith L.; Rash, Clarence E.

    2005-05-01

    As part of a 2003 survey during Operation Iraqi Freedom, forty AH-64 Apache aviators were interviewed regarding their experience using the AH-64"s monocular helmet-mounted display (HMD). Participants represented a total of 8564 flight hours and 2260 combat hours in the OIF theatre of operation. The interview consisted of 12 questions that addressed previously identified potential problem areas (e.g., maintaining full field-of-view [FOV], combiner breakage, and sensor slew rate) and requested participant opinion on the best and worst features of the IHADSS, day versus night use of the IHADSS, and the acceptance of a hypothetical binocular IHADSS design. Participants expressed a desire for a larger FOV; emphasized the impact of poor helmet fit on ability to achieve and maintain a full FOV; decried the overall performance of the current FLIR sensors; and reported that the current slew rates for the PNVS and TADS are slower than desired (worse for TADS), necessitating compensation in normal head movement rates.

  9. Public sources of information and information needs for pandemic influenza A(H1N1).

    PubMed

    Wong, Li Ping; Sam, I-Ching

    2010-12-01

    Providing health information during disease outbreaks is a fundamental component of outbreak control strategies. This study aimed to explore sources of influenza A(H1N1)-related information, specific information needs and preferences of the lay public during the peak of the outbreak. A cross-sectional, population-based, computer-assisted telephone interview of 1,050 respondents was conducted in Malaysia between July 11 and September 12, 2009. Newspaper, television and family were three main sources of information about A(H1N1). There were substantial ethnic differences; the Malays were significantly more likely to identify television as main source, while newspapers and family were identified as the main sources by the Chinese and Indians, respectively. Overall, the two main information needs identified were prevention and treatment. The Malays expressed lesser need for overall information than other ethnic groups. The three most preferred sources of information were television, newspapers and healthcare providers. There were significant positive correlations between amount of information received with knowledge (r = 0.149), perceived susceptibility to infection (r = 0.177), and other behavioral responses. Health information dissemination should be dedicated to meeting the information needs of diverse sociodemographic and ethnic groups. The findings highlight the importance of providing information that increases awareness and behavioral changes in disease prevention yet reduce fear.

  10. [Direct immunofluorescence assay performance in diagnosis of the Influenza A(H1N1) virus].

    PubMed

    Pianciola, Luis; González, Gladys; Mazzeo, Melina; Navello, Mariano; Quidel, Natalia; Bulgheroni, María Fernanda

    2010-06-01

    By 25 April 2009, less than one month after the first human with Influenza A(H1N1) virus was detected in Mexico, the disease had already spread to more than 40 countries, with over 10,000 cases reported. Due to its unpredictability, this type of virus requires appropriate, reliable, and safe diagnostic methods that are also accessible to clinical laboratories. Through the analysis of 291 samples taken from patients with suspected Influenza A(H1N1) virus infection in Neuquén, Argentina, this study compares the two diagnostic methods used simultaneously: direct immunofluorescence assay (DFA) and real-time polymerase chain reaction (RT-PCR). DFA had a sensitivity of 44.4%, a specificity of 99.6%, a positive predictive value of 95.2%, and a negative predictive value of 90.7%. Positive results obtained with this method can be considered true positives. A negative result does not rule out the presence of the virus. In this case, the sample should be examined by RT-PCR. Out of a total of 291 samples, there were 45 positive results with RT-PCR and 21 positive results with DFA.

  11. 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

  12. Advanced driver assistance system for AHS over communication links with random packet dropouts

    NASA Astrophysics Data System (ADS)

    Srinivasan, Seshadhri; Ayyagari, Ramakalyan

    2014-12-01

    In this paper, we propose an advanced driver assist system (ADAS) for platoon based automated highway system (AHS) with packet loss in inter-vehicle communication. Using the concept of rigidity, we first show that vehicles in a platoon tend to fall apart in the event of a packet loss among vehicles. To overcome this, we propose an estimation based dynamic platooning algorithm which employs the state estimate to maintain the platoon. Communication among the vehicle is reduced by using minimum spanning tree (MST) in state estimation algorithm. Effectiveness of the proposed ADAS scheme is illustrated by simulation wherein, dynamic platoons of holonomic vehicles with integrator dynamics are considered. Simulation studies indicate that the proposed algorithm maintains the platoon up to a packet loss rate of 48%. State transmission scheme proposed in our algorithm has three significant advantages, they are: (1) it handles packet loss in inter-vehicle communication, (2) reduces the effect of error in measured output, and (3) reduces the inter-vehicle communication. These advantages significantly increase the reliability and safety of the AHS.

  13. 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.

  14. Enhanced influenza surveillance on Réunion Island (southern hemisphere) in the context of the emergence of influenza A(H1N1)v.

    PubMed

    D'Ortenzio, E; Do, C; Renault, P; Weber, F; Filleul, L

    2009-06-11

    With the winter season on the southern hemisphere that starts in Reunion Island in June seasonal influenza activity usually increases shortly afterwards. The new influenza A(H1N1)v virus is rapidly spreading worldwide and may reach the island during the coming winter season. We have therefore enhanced influenza surveillance to detect the introduction of influenza A(H1N1)v, monitor its spread and impact on public health and characterise potential viral changes, particularly if seasonal influenza A(H1N1), resistant to oseltamivir, co-circulates with A(H1N1)v. PMID:19531342

  15. Predicting AH1N1 2009 influenza epidemic in Southeast Europe

    PubMed Central

    Smoljanović, Mladen; Smoljanović, Ankica; Mlikotić, Marijana

    2011-01-01

    Aim To use the data on the AH1N1 2009 influenza epidemic in the Southern hemisphere countries to predict the course and size of the upcoming influenza epidemic in South-Eastern Europe (SEE) countries and other regions of the World with temperate climate. Method We used a comparative epidemiological method to evaluate accessible electronic data on laboratory-confirmed deaths from AH1N1 2009 influenza in the seasons 2009/2010 and 2010/2011. The studied SEE countries were Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Hungary, Kosovo, Macedonia, Montenegro, Romania, Serbia, and Slovenia, while Southern hemisphere countries were Argentina, Australia, Chile, New Zealand, Paraguay, Uruguay, and South Africa. Results In influenza season 2009/2010, Southern hemisphere countries with temperate climate reported 1187 laboratory-confirmed influenza AH1N1 2009 deaths (mortality rate 0.84/100 000; 95% confidence interval [CI], 0.50-1.24). SEE countries with similar climatic conditions reported 659 deaths and similar mortality rates (0.86/100 000, 95% CI, 0.83-1.10). In the whole Europe without the Commonwealth of Independent States countries (CIS, former Soviet Union), there were 3213 deaths (0.60/100 000; 95% CI, 0.65-0.93). In 2010/2011, Southern hemisphere countries reported 94 laboratory-confirmed deaths (mortality rate 0.07/100 000; 95% CI, 0.02-0.28) or only 7.9% of the previous season. SEE countries by the end of the 11th epidemiological week of 2010/2011 season reported 489 laboratory-confirmed deaths, with a mortality rate of 0.64/100 000 (95% CI, 0.26-0.96) or 74.2% of the previous season, which was significantly higher than in the Southern hemisphere countries (χ21 = 609.1, P < 0.001). In Europe without CIS countries, there were 1836 deaths, with a mortality rate of 0.34/100 000 (χ2 = 153.3, P < 0.001 vs SEE countries). Conclusion In the 2009/2010 season, SEE countries and Southern hemisphere countries had similar influenza

  16. 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.

  17. Orbital Period Changes and Their Evolutionary Status for the Weak-Contact Binaries. III. AO Camelopardalis and AH Tauri

    NASA Astrophysics Data System (ADS)

    Yang, Y.-G.; Wei, J.-Y.; Kreiner, J. M.; Li, H.-L.

    2010-01-01

    In this paper, we presented multicolor photometric observations for two eclipsing binaries, AO Camelopardalis and AH Tauri, obtained on 2008 December 16 and 17. Using the Wilson-Devinney Code, the photometric solution of AH Tau was determined from our new CCD data. The mass ratio and the fill-out factor are q = 0.503(±0.003) and f = 10.8%(±0.1%), respectively. This indicates that AH Tau is in weak contact. For the weak-contact binary AO Cam, BVI light curves clearly show a difference in the heights of the maxima (i.e., the O'Connell effect), which may be explained by spot activity. By analyzing the O - C curves for AO Cam and AH Tau, it is found that the orbital periods appear to show a secular period decrease with a cyclic variation. The observed period modulation is ΔP/P ~ 10-6. For AO Cam, the cyclic oscillation with a short period of 7.63(±0.07) yr and a low amplitude of 0fd0019(±0fd0003) may be preferably attributed to the cyclic magnetic activity. The period and amplitude of the cyclic variation for AH Tau are 45.8(±1.1) yr and 0fd0171(±0fd0005), which may more likely result from the light-time effect via a third body. The secular period decrease rates are dP/dt = -1.26(±0.04) × 10-7 days yr -1 for AO Cam and dP/dt = -6.98(±0.07) × 10-8 days yr -1 for AH Tau. This kind of period decrease can be plausibly explained by the mass transfer from the primary to the secondary, and may result in the system evolving into a deep contact configuration.

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

    SciTech Connect

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

    2014-07-01

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

  19. Detection of Nonhemagglutinating Influenza A(H3) Viruses by Enzyme-Linked Immunosorbent Assay in Quantitative Influenza Virus Culture

    PubMed Central

    Els, C.; Sprong, L.; van Beek, R.; van der Vries, E.; Osterhaus, A. D. M. E.; Rimmelzwaan, G. F.

    2014-01-01

    To assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. Typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutinin (HA). This readout method is no longer adequate, since an increasing number of currently circulating influenza A virus H3 subtype (A[H3]) viruses display a reduced capacity to agglutinate erythrocytes. Here, we report the magnitude of this problem by analyzing the frequency of HA-deficient A(H3) viruses detected in The Netherlands from 1999 to 2012. Furthermore, we report the development and validation of an alternative method for monitoring the production of progeny influenza virus in quantitative virus cultures, which is independent of the capacity to agglutinate erythrocytes. This method is based on the detection of viral nucleoprotein (NP) in virus culture plates by enzyme-linked immunosorbent assay (ELISA), and it produced results similar to those of the hemagglutination assay using strains with good HA activity, including A/Brisbane/059/07 (H1N1), A/Victoria/210/09 (H3N2), other seasonal A(H1N1), A(H1N1)pdm09, and the majority of A(H3) virus strains isolated in 2009. In contrast, many A(H3) viruses that have circulated since 2010 failed to display HA activity, and infectious virus titers were determined only by detecting NP. The virus culture ELISA described here will enable efficacy testing of new antiviral compounds in clinical trials during seasons in which nonhemagglutinating influenza A viruses circulate. PMID:24622097

  20. Detection of nonhemagglutinating influenza a(h3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture.

    PubMed

    van Baalen, C A; Els, C; Sprong, L; van Beek, R; van der Vries, E; Osterhaus, A D M E; Rimmelzwaan, G F

    2014-05-01

    To assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. Typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutinin (HA). This readout method is no longer adequate, since an increasing number of currently circulating influenza A virus H3 subtype (A[H3]) viruses display a reduced capacity to agglutinate erythrocytes. Here, we report the magnitude of this problem by analyzing the frequency of HA-deficient A(H3) viruses detected in The Netherlands from 1999 to 2012. Furthermore, we report the development and validation of an alternative method for monitoring the production of progeny influenza virus in quantitative virus cultures, which is independent of the capacity to agglutinate erythrocytes. This method is based on the detection of viral nucleoprotein (NP) in virus culture plates by enzyme-linked immunosorbent assay (ELISA), and it produced results similar to those of the hemagglutination assay using strains with good HA activity, including A/Brisbane/059/07 (H1N1), A/Victoria/210/09 (H3N2), other seasonal A(H1N1), A(H1N1)pdm09, and the majority of A(H3) virus strains isolated in 2009. In contrast, many A(H3) viruses that have circulated since 2010 failed to display HA activity, and infectious virus titers were determined only by detecting NP. The virus culture ELISA described here will enable efficacy testing of new antiviral compounds in clinical trials during seasons in which nonhemagglutinating influenza A viruses circulate.

  1. 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

  2. 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.

  3. Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen independent signaling and growth in (C4-2) prostate cancer cells

    PubMed Central

    Tran, Cindy; Richmond, Oliver; Aaron, LaTayia; Powell, Joann B.

    2013-01-01

    The aryl hydrocarbon receptor is a member of the basic-helix-loop-helix family of transcription factors. AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD). AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells. Immunoblot analysis shows that AhR expression is increased in androgen independent (C4-2) prostate cancer cells when compared to androgen sensitive (LNCaP) cells. RT-PCR studies revealed constitutive AhR signaling in C4-2 cells without the ligand induced activation required in LNCaP cells. A reduction of AhR activity by short RNA mediated silencing in C4-2 cells reduced expression of both AhR and androgen responsive genes. The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus. Furthermore, the forced decrease in AhR expression resulted in a 50% decline in the growth rate of C4-2 cells. These data indicates that AhR is required to maintain hormone independent signaling and growth by the androgen receptor in C4-2 cells. Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer. PMID:23266674

  4. Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study

    PubMed Central

    Trotta, Francesco; Da Cas, Roberto; Spila Alegiani, Stefania; Gramegna, Maria; Venegoni, Mauro; Zocchetti, Carlo

    2014-01-01

    Objective To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy. Design Historical cohort study. Setting Singleton pregnancies of the resident population of the Lombardy region of Italy. Participants All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes. Main outcome measures Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations. Results Among the 86 171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31). Conclusions Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations. PMID:24874845

  5. 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.

  6. Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity.

    PubMed

    Liu, Jun; Huang, Feng; Zhang, Junsong; Tan, Likai; Lu, Gen; Zhang, Xu; Zhang, Hui

    2016-06-01

    Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity. Based on a phylogenetic analysis, we show a special evolutionary feature of the H1N1pdm09 PA gene, which clustered with those of the novel H7N9 virus and related H9N2 viruses, rather than in the outgroup as the H1N1pdm09 genes do on the phylogenetic trees of other vRNP genes. Using a minigenome system of the novel H7N9 virus, we further demonstrate that replacement of its PA gene significantly enhanced its polymerase activity, whereas replacement of the other vRNP genes reduced its polymerase activity. We also show that the residues of PA evolutionarily conserved between H1N1pdm09 and the novel H7N9 virus are associated with attenuated or neutral polymerase activity. The mutations associated with the increased activity of the novel H7N9 polymerase are characteristic of the H1N1pdm09 gene, and are located almost adjacent to the surface of the PA protein. Our results suggest that the novel H7N9 virus has more effective PB1, PB2, and NP genes than H1N1pdm09, and that H1N1pdm09-like PA mutations enhance the novel H7N9 polymerase function.

  7. 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 Central

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

    2015-01-01

    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. PMID:25944559

  8. Effect of planform taper on hover performance of an advanced AH-64 model rotor

    NASA Technical Reports Server (NTRS)

    Kelley, Henry L.

    1987-01-01

    The hover performance of a 27 percent scale model baseline rotor and advanced rotor with a 3:1 tapered tip (TR3) for the AH-64 attack helicopter was investigated and compared. Hover results from a previously tested advanced rotor with a 5:1 tapered tip (TR5) were also compared. Rotor thrust was varied over a range for two tip Mach numbers. The results indicated that the TR3 blades had improved performance compared with the TR5 blades, and both the TR3 and TR5 blades were superior to the baseline rotor. The additional margin in performance for the TR3 blades was likely due to an increase in blade area and Reynolds number in the tip region of the blades.

  9. AHS, Annual Forum, 47th, Phoenix, AZ, May 6-8, 1991, Proceedings. Vols. 1 2

    SciTech Connect

    Not Available

    1991-01-01

    The present conference on helicopter technologies discusses a 3D analysis of a rotor in forward flight, V-22 flight-test aerodynamics, the identification of higher-order helicopter dynamics using linear modeling methods, the evaluation of novel statistical methods for safe-life reliability, a full-scale airframe high cycle fatigue test methodology, and practical robustness testing for helicopter flight control systems. Also discussed are the mechanics of a curved-fiber composite, expanding Marine Corps roles for the AH-1W helicopter, rotorcraft maneuverability/agility-survivability sensitivity analysis, the prototype development of the helicopter air-to-air value-driven engagement model, V-22 effectiveness in land combat operations-support, the design manufacture of an advanced thermoplastic horizontal stabilator, a full-mission simulation data system, stress analysis of composite rotor systems, and an NDT assessment of the V-22.

  10. Cluster analysis of the origins of the new influenza A(H1N1) virus.

    PubMed

    Solovyov, A; Palacios, G; Briese, T; Lipkin, W I; Rabadan, R

    2009-05-28

    In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia. PMID:19480812

  11. A.H. Cottrell at Harwell in the mid-1950s

    NASA Astrophysics Data System (ADS)

    Hull, Derek

    2013-09-01

    A.H. Cottrell led a large team of scientists and engineers as Deputy Director of the Metallurgy Division of the Atomic Energy Research Establishment at Harwell, between 1955 and 1958. The team sought to develop a fundamental understanding of the effect of aggressive operating conditions on the properties and behaviour of materials used in the construction of reactors, which provided important and critical insights into their design, operation and safety. The story is told through the experiences and research activities of one of Cottrell's junior research staff. It offers an insight into the contributions made by Cottrell to the science and technology regarding materials used in the early days of building reactors for the generation of nuclear energy.

  12. Transmission and control in an institutional pandemic influenza A(H1N1) 2009 outbreak.

    PubMed

    Arinaminpathy, N; Raphaely, N; Saldana, L; Hodgekiss, C; Dandridge, J; Knox, K; McCarthy, N D

    2012-06-01

    A pandemic influenza A(H1N1) 2009 outbreak in a summer school affected 117/276 (42%) students. Residential social contact was associated with risk of infection, and there was no evidence for transmission associated with the classroom setting. Although the summer school had new admissions each week, which provided susceptible students the outbreak was controlled using routine infection control measures (isolation of cases, basic hygiene measures and avoidance of particularly high-risk social events) and prompt treatment of cases. This was in the absence of chemoprophylaxis or vaccination and without altering the basic educational activities of the school. Modelling of the outbreak allowed estimation of the impact of interventions on transmission. These models and follow-up surveillance supported the effectiveness of routine infection control measures to stop the spread of influenza even in this high-risk setting for transmission. PMID:21859502

  13. Performance and Maqasid al-Shari'ah's Pentagon-Shaped Ethical Measurement.

    PubMed

    Bedoui, Houssem Eddine; Mansour, Walid

    2015-06-01

    Business performance is traditionally viewed from the one-dimensional financial angle. This paper develops a new approach that links performance to the ethical vision of Islam based on maqasid al-shari'ah (i.e., the objectives of Islamic law). The approach involves a Pentagon-shaped performance scheme structure via five pillars, namely wealth, posterity, intellect, faith, and human self. Such a scheme ensures that any firm or organization can ethically contribute to the promotion of human welfare, prevent corruption, and enhance social and economic stability and not merely maximize its own performance in terms of its financial return. A quantitative measure of ethical performance is developed. It surprisingly shows that a firm or organization following only the financial aspect at the expense of the others performs poorly. This paper discusses further the practical instances of the quantitative measurement of the ethical aspects of the system taken at an aggregate level.

  14. Cohort vision study of Apache AH Mk1 pilots: protocol and methodology

    NASA Astrophysics Data System (ADS)

    Hiatt, Keith L.; Braithwaite, Malcolm G.; Crowley, John S.; Rash, Clarence E.; van de Pol, Corina; Ranchino, Daniel J.; Statz, William K.; Eke, Allison J.

    2002-08-01

    A collaborative occupational health study has been undertaken by Headquarters Director Army Aviation, Middle Wallop, UK, and the U.S. Army Aeromedical Research Laboratory, Fort Rucker, Alabama, to determine if the use of the monocular helmet-mounted display in the Apache AH Mk 1 attack helicopter has any long-term (10-year) effect on visual performance. This paper describes the protocol, methodology, development and initial execution phase of this study. The test methodology consists primarily of a battery of vision tests selected to capture changes in visual performance (with an emphasis on binocular visual functions) of Apache aviators over their flight career. It is anticipated that the number of Apache aviators will level out to approximately 70 by the end of the first three years of the study. Non-Apache aviators will serve as a control group.

  15. Correlation of AH-1G airframe flight vibration data with a coupled rotor-fuselage analysis

    NASA Technical Reports Server (NTRS)

    Sangha, K.; Shamie, J.

    1990-01-01

    The formulation and features of the Rotor-Airframe Comprehensive Analysis Program (RACAP) is described. The analysis employs a frequency domain, transfer matrix approach for the blade structural model, a time domain wake or momentum theory aerodynamic model, and impedance matching for rotor-fuselage coupling. The analysis is applied to the AH-1G helicopter, and a correlation study is conducted on fuselage vibration predictions. The purpose of the study is to evaluate the state-of-the-art in helicopter fuselage vibration prediction technology. The fuselage vibration predicted using RACAP are fairly good in the vertical direction and somewhat deficient in the lateral/longitudinal directions. Some of these deficiencies are traced to the fuselage finite element model.

  16. Denhaminols A-H, dihydro-β-agarofurans from the endemic Australian rainforest plant Denhamia celastroides.

    PubMed

    Levrier, Claire; Sadowski, Martin C; Nelson, Colleen C; Healy, Peter C; Davis, Rohan A

    2015-01-23

    Eight new dihydro-β-agarofurans, denhaminols A-H (1-8), were isolated from the leaves of the Australian rainforest tree Denhamia celastroides. The chemical structures of 1-8 were elucidated following analysis of 1D/2D NMR and MS data. The absolute configuration of denhaminol A (1) was determined by single-crystal X-ray crystallography. All compounds were evaluated for cytotoxic activity against the human prostate cancer cell line LNCaP, using live-cell imaging and metabolic assays. Denhaminols A (1) and G (7) were also tested for their effects on the lipid content of LNCaP cells. This is the first report of secondary metabolites from D. celastroides.

  17. Thermoelectrochemical simulations of performance and abuse in 50-Ah automotive cells

    NASA Astrophysics Data System (ADS)

    Kim, Sun Ung; Albertus, Paul; Cook, David; Monroe, Charles W.; Christensen, Jake

    2014-12-01

    The performance and thermal response of large-scale GS-Yuasa LEV50 50-Ah NMC automotive battery cells were investigated via simulation. To evaluate local transient temperature distributions, the Dualfoil model was coupled to local energy-balance equations. At similar C rates the difference between maximum and minimum temperature in the LEV50 was found to be higher than that in an 18650 cell with identical chemistry. Unlike thinner prismatic lithium ion batteries, the temperature variation through the cell thickness in the large-format cell was not negligible (∼5 °C at 4C discharge). Because of the non-uniform temperature distribution within the jellyroll, the risk of lithium plating at high charging rates and low ambient temperatures may be greater toward the jellyroll exterior. Simulations of thermal abuse (oven test) of the large cell showed a delayed thermal response relative to the 18650, but also indicated a lower onset temperature for thermal runaway.

  18. Structure of native laccase B from Trametes sp. AH28-2

    PubMed Central

    Ge, Honghua; Gao, Yongxiang; Hong, Yuzhi; Zhang, Min; Xiao, Yazhong; Teng, Maikun; Niu, Liwen

    2010-01-01

    Fungal laccases are oxidoreductases that belong to the multinuclear copper-containing oxidases. They are able to oxidize a wide range of substrates, preferably phenolic compounds, which makes them suitable for employment in the bioremediation of soil and water as well as in other biotechnological applications. Here, the structural analysis of natural laccase B (LacB) from Trametes sp. AH28-2 is presented. This structure provides the opportunity to study the natural post-translational modifications of the enzyme. The overall fold shows a high homology to those of previously analyzed laccases with known three-dimensional structure. However, LacB contains a new structural element, a protruding loop near the substrate-binding site, compared with the previously reported laccase structures. This unique structural feature may be involved in modulation of the substrate recognition of LacB. PMID:20208154

  19. Development of a long life 35 Ah capacity VRLA battery for load-leveling applications

    NASA Astrophysics Data System (ADS)

    Nakayama, Yasuhide; Takahashi, Sawako; Hirakawa, Kenji; Yamaguchi, Yoshiaki

    A load-leveling (LL) system is needed for the effective use of electric power to preserve the environment in Japan. Although the valve regulated lead-acid (VRLA) battery is considered to be one of the suitable candidates, high requirements of long cycle life such as 2000 cycles or a calendar life of 7 years needed to be solved. We are currently developing a new VRLA battery for this application, and have succeeded in achieving over 2000 cycles with a 35 Ah class VRLA battery. It was confirmed by the detailed investigation after a cycling test of the battery that this cycle performance was achieved by improving the charge acceptance of the negative plate, avoiding the grid corrosion by applying an optimized charge condition.

  20. The origin and global emergence of adamantane resistant A/H3N2 influenza viruses

    PubMed Central

    Nelson, Martha I.; Simonsen, Lone; Viboud, Cécile; Miller, Mark A.; Holmes, Edward C.

    2009-01-01

    Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza viruses currently exceeds 90% in the United States and multiple Asian countries. Adamantane resistance is associated with a single amino acid change (S31N) in the M2 protein, which was shown to rapidly disseminate globally in 2005 in association with a genome reassortment event. However, the exact origin of influenza A/H3N2 viruses carrying the S31N mutation has not been characterized, particularly in South-East Asia. We therefore conducted a phylogenetic analysis of the HA, NA, and M1/2 segments of viral isolates collected between 1997-2007 from temperate localities in the Northern hemisphere (New York State, United States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629 isolates) and a subtropical locality in South-East Asia (Hong Kong, 281 isolates). We find that although the S31N mutation was independently introduced at least 11 times, the vast majority of resistant viruses now circulating globally descend from a single introduction that was first detected in the summer of 2003 in Hong Kong. These resistant viruses were continually detected in Hong Kong throughout 2003-2005, acquired a novel HA through reassortment during the first part of 2005, and thereafter spread globally. The emergence and persistence of adamantane-resistant viruses in Hong Kong further supports a source-sink model of global influenza virus ecology, in which South-East Asia experiences continuous viral activity and repeatedly seeds epidemics in temperate areas. PMID:19394063

  1. Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?

    PubMed Central

    Ilyushina, Natalia A.; Ducatez, Mariette F.; Rehg, Jerold E.; Marathe, Bindumadhav M.; Marjuki, Henju; Bovin, Nicolai V.; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37°C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated. PMID:21116343

  2. Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study (AHS) data.

    PubMed

    Sorahan, Tom

    2015-02-01

    A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993-2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use. PMID:25635915

  3. An update on swine-origin influenza virus A/H1N1: a review.

    PubMed

    Schnitzler, Sebastian U; Schnitzler, Paul

    2009-12-01

    Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1.

  4. 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).

  5. Precursor systems analyses of automated highway systems: Commercial vehicle and transit ahs analysis. Volume 6. Final report, September 1993-February 1995

    SciTech Connect

    Bottiger, F.; Chemnitz, H.D.; Doorman, J.; Franke, U.; Zimmerman, T.

    1995-03-01

    This document is the final report of the Automated Highway System (AHS). The activities of Commercial Vehicle and Transit AHS Analysis are reported on in this document. This document type is resource materials. This volume is the six in a series. There are nine other volumes in the series.

  6. 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.

  7. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

    PubMed

    Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

    2015-12-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus.

  8. 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

  9. 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.

  10. Responses to threat of influenza A(H7N9) and support for live poultry markets, Hong Kong, 2013.

    PubMed

    Wu, Peng; Fang, Vicky J; Liao, Qiuyan; Ng, Diane M W; Wu, Joseph T; Leung, Gabriel M; Fielding, Richard; Cowling, Benjamin J

    2014-05-01

    We conducted a population survey in Hong Kong to gauge psychological and behavioral responses to the threat of influenza A(H7N9) and support for closure of live poultry markets. We found low anxiety and low levels of exposure to live poultry but mixed support for permanent closure of the markets.

  11. Increased Number of Human Cases of Influenza Virus A(H5N1) Infection, Egypt, 2014-15.

    PubMed

    Refaey, Samir; Azziz-Baumgartner, Eduardo; Amin, Marwa Mohamed; Fahim, Manal; Roguski, Katherine; Elaziz, Hanaa Abu Elsood Abd; Iuliano, A Danielle; Salah, Noha; Uyeki, Timothy M; Lindstrom, Steven; Davis, Charles Todd; Eid, Alaa; Genedy, Mohamed; Kandeel, Amr

    2015-12-01

    During November 2014-April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry. PMID:26584397

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

    PubMed Central

    Kimura, Eiki; Ding, Yunjie; Tohyama, Chiharu

    2016-01-01

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

  13. Increased Number of Human Cases of Influenza Virus A(H5N1) Infection, Egypt, 2014-15.

    PubMed

    Refaey, Samir; Azziz-Baumgartner, Eduardo; Amin, Marwa Mohamed; Fahim, Manal; Roguski, Katherine; Elaziz, Hanaa Abu Elsood Abd; Iuliano, A Danielle; Salah, Noha; Uyeki, Timothy M; Lindstrom, Steven; Davis, Charles Todd; Eid, Alaa; Genedy, Mohamed; Kandeel, Amr

    2015-12-01

    During November 2014-April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry.

  14. 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.

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

    PubMed Central

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

    2016-01-01

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

  16. Aluminum-induced programmed cell death promoted by AhSAG, a senescence-associated gene in Arachis hypoganea L.

    PubMed

    Zhan, Jie; He, Hu-Yi; Wang, Tian-Ju; Wang, Ai-Qin; Li, Chuang-Zhen; He, Long-Fei

    2013-09-01

    Programmed cell death (PCD) is a foundational cellular process in plant development and elimination of damaged cells under environmental stresses. In this study, Al induced PCD in two peanut (Arachis hypoganea L.) cultivars Zhonghua 2 (Al-sensitive) and 99-1507 (Al-tolerant) using DNA ladder, TUNEL detection and electron microscopy. The concentration of Al-induced PCD was lower in Zhonghua 2 than in 99-1507. AhSAG, a senescence-associated gene was isolated from cDNA library of Al-stressed peanut with PCD. Open reading frame (ORF) of AhSAG was 474bp, encoding a SAG protein composed of 157 amino acids. Compared to the control and the antisense transgenic tobacco plants, the fast development and blossom of the sense transgenic plants happened to promote senescence. The ability of Al tolerance in sense transgenic tobacco was lower than in antisense transgenic tobacco according to root elongation and Al content analysis. The expression of AhSAG-GFP was higher in sense transgenic tobacco than in antisense transgenic tobacco. Altogether, these results indicated that there was a negative relationship between Al-induced PCD and Al-resistance in peanut, and the AhSAG could induce or promote the occurrence of PCD in plants. PMID:23849118

  17. Efficacy of Inactivated Swine Influenza Virus Vaccines Against the 2009 A/H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North Ameri...

  18. 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…

  19. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh

    PubMed Central

    Lenny, Brian J.; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M.; Alam, S.M. Rabiul; Hasan, M. Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G.

    2015-01-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus. PMID:26583371

  20. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

    PubMed

    Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

    2015-12-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus. PMID:26583371

  1. Identification of ah receptor agonists in soil of E-waste recycling sites from Taizhou area in China.

    PubMed

    Shen, Chaofeng; Huang, Shengbiao; Wang, Zijian; Qiao, Min; Tang, Xianjin; Yu, Chunna; Shi, Dezhi; Zhu, Youfeng; Shi, Jiyan; Chen, Xincai; Setty, Karen; Chen, Yingxu

    2008-01-01

    In recent years, increasing concern has surrounded the consequences of improper electric and electronic waste (e-waste) disposal. In order to mitigate or remediate the potentially severe toxic effects of e-waste recycling on the environment, organisms, and humans, many contaminated sites must first be well-characterized. In this study, soil samples were taken from Taizhou city, one of the largest e-waste disposal centers in China, which was involved in recycling for nearly 30 years. The extracts of the samples were assayed for aryl hydrocarbon receptor (AhR)-mediated ethoxyresorufin-O-deethylase (EROD) induction in the rat hepatoma cell line H4IIE. Some of the target AhR agonists, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs), were instrumentally analyzed as well. The cause-effect relationship and dose-response relationship between the chemical concentrations of AhR agonists and observed EROD activity were examined. The results showed that soil extracts could induce AhR activity significantly, and the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQcal) were perfectly correlated to bioassay-derived TCDD equivalents (TEQbio; R = 0.96, P < 0.001), which indicated that the known AhR agonists could account for the observed responses. Among different contributors, PCBs accounted for 87.2-98.2% and PCDD/Fs contributed 1.7-11.6% of TEQcal, while the contribution of PAHs could almost be neglected. Under these conditions, a quantitative dose-effect relationship between TEQ(PCB) and EROD activity could be evaluated, suggesting that the observed AhR effect was mainly caused by PCBs. Further source identification by congener profiles analysis showed that the crude dismantling of electric power devices and open burning of electric wires and printed circuit boards may be the main sources of these dioxin-like compounds. This study suggests that

  2. 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

  3. Metabolic characterization of AH-7921, a synthetic opioid designer drug: in vitro metabolic stability assessment and metabolite identification, evaluation of in silico prediction, and in vivo confirmation.

    PubMed

    Wohlfarth, Ariane; Scheidweiler, Karl B; Pang, Shaokun; Zhu, Mingshe; Castaneto, Marisol; Kronstrand, Robert; Huestis, Marilyn A

    2016-08-01

    AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a new synthetic opioid and has led to multiple non-fatal and fatal intoxications. To comprehensively study AH-7921 metabolism, we assessed human liver microsome (HLM) metabolic stability, determined AH-7921's metabolic profile after human hepatocytes incubation, confirmed our findings in a urine case specimen, and compared results to in silico predictions. For metabolic stability, 1 µmol/L AH-7921 was incubated with HLM for up to 1 h; for metabolite profiling, 10 µmol/L was incubated with pooled human hepatocytes for up to 3 h. Hepatocyte samples were analyzed by liquid chromatography quadrupole/time-of-flight high-resolution mass spectrometry (MS). High-resolution full scan MS and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot™ (SCIEX) using multiple data processing algorithms. The presence of AH-7921 and metabolites was confirmed in the urine case specimen. In silico prediction of metabolite structures was performed with MetaSite™ (Molecular Discovery). AH-7921 in vitro half-life was 13.5 ± 0.4 min. We identified 12 AH-7921 metabolites after hepatocyte incubation, predominantly generated by demethylation, less dominantly by hydroxylation, and combinations of different biotransformations. Eleven of 12 metabolites identified in hepatocytes were found in the urine case specimen. One metabolite, proposed to be di-demethylated, N-hydroxylated and glucuronidated, eluted after AH-7921 and was the most abundant metabolite in non-hydrolyzed urine. MetaSite™ correctly predicted the two most abundant metabolites and the majority of observed biotransformations. The two most dominant metabolites after hepatocyte incubation (also identified in the urine case specimen) were desmethyl and di-desmethyl AH-7921. Together with the glucuronidated metabolites, these are likely suitable analytical targets for documenting AH-7921 intake. Copyright © 2015

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

    PubMed

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

    2014-07-01

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

  5. 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

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

    PubMed

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

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (-105/+1 base pair). Fgf21-null mice administered 200μg/kg of TCDD died within 20days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. PMID:24769090

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

    SciTech Connect

    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-VP16 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.

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

    PubMed

    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

  9. 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

  10. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses.

    PubMed

    Butler, Jeff; Hooper, Kathryn A; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G; McCaw, James M; Bloom, Jesse D; Hurt, Aeron C

    2014-04-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide. PMID:24699865

  11. Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

    PubMed Central

    Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cécile; Simonsen, Lone; Tamerius, James; Miller, Mark A.; Borja-Aburto, Víctor H.

    2011-01-01

    Background Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. Methods and Findings We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school

  12. Timeliness of contact tracing among flight passengers for influenza A/H1N1 2009

    PubMed Central

    2011-01-01

    Background During the initial containment phase of influenza A/H1N1 2009, close contacts of cases were traced to provide antiviral prophylaxis within 48 h after exposure and to alert them on signs of disease for early diagnosis and treatment. Passengers seated on the same row, two rows in front or behind a patient infectious for influenza, during a flight of ≥ 4 h were considered close contacts. This study evaluates the timeliness of flight-contact tracing (CT) as performed following national and international CT requests addressed to the Center of Infectious Disease Control (CIb/RIVM), and implemented by the Municipal Health Services of Schiphol Airport. Methods Elapsed days between date of flight arrival and the date passenger lists became available (contact details identified - CI) was used as proxy for timeliness of CT. In a retrospective study, dates of flight arrival, onset of illness, laboratory diagnosis, CT request and identification of contacts details through passenger lists, following CT requests to the RIVM for flights landed at Schiphol Airport were collected and analyzed. Results 24 requests for CT were identified. Three of these were declined as over 4 days had elapsed since flight arrival. In 17 out of 21 requests, contact details were obtained within 7 days after arrival (81%). The average delay between arrival and CI was 3,9 days (range 2-7), mainly caused by delay in diagnosis of the index patient after arrival (2,6 days). In four flights (19%), contacts were not identified or only after > 7 days. CI involving Dutch airlines was faster than non-Dutch airlines (P < 0,05). Passenger locator cards did not improve timeliness of CI. In only three flights contact details were identified within 2 days after arrival. Conclusion CT for influenza A/H1N1 2009 among flight passengers was not successful for timely provision of prophylaxis. CT had little additional value for alerting passengers for disease symptoms, as this information already was provided

  13. Substantial Morbidity and Mortality Associated with Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity

    PubMed Central

    Dávila, Javier; Chowell, Gerardo; Borja-Aburto, Víctor H.; Viboud, Cécile; Grajales Muñiz, Concepciòn; Miller, Mark

    2014-01-01

    Background: A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild 2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real time. Methods: We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection (SARI), laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated the reproduction number (R) based on the growth rate of daily case incidence by date of symptoms onset. Results: A total of 7,886 SARI hospitalizations and 529 inpatient-deaths (3.2%) were reported between 01-October 2013 and 31-January 2014 (resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed A/H1N1-positive deaths per 100,000). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y (SD=20.3) for hospitalizations and 49.2 y (SD=16.7) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, compared to the 2011-12 A/H1N1 epidemic (Chi-square test, P

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

    PubMed

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

    2014-02-01

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

  15. Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1α signaling node

    PubMed Central

    Vorrink, Sabine U.; Domann, Frederick E.

    2014-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the responses to toxic environmental chemicals such as TCDD or dioxin-like PCBs. To regulate gene expression, the AhR requires its binding partner, the aryl hydrocarbon receptor nuclear translocator (ARNT). ARNT is also required by the hypoxia-inducible factor-1α (HIF-1α), a crucial regulator of responses to conditions of reduced oxygen. The important role of ARNT in both the AhR and HIF-1α signaling pathways establishes a meaningful foundation for a possible crosstalk between these two vitally important signaling pathways. This crosstalk might lead to interference between the two signaling pathways and thus might play a role in the variety of cellular responses after exposure to AhR ligands and reduced oxygen availability. This review focuses on studies that have analyzed the effect of low oxygen environments and hypoxiamimetic agents on AhR signaling and conversely, the effect of AhR ligands, with a special emphasis on PCBs, on HIF-1α signaling. We highlight studies that assess the role of ARNT, elucidate the mechanism of the crosstalk, and discuss the physiological implications for exposure to AhR-inducing compounds in the context of hypoxia. PMID:24824450

  16. 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

  17. Molecular characterization of the aryl hydrocarbon receptor (AhR) pathway in goldfish (Carassius auratus) exposure to TCDD: the mRNA and protein levels.

    PubMed

    Lu, Ming; Chang, Ziwei; Bae, Min-Ji; Oh, Seung Min; Chung, Kyu-Hyuck; Park, Jang-Su

    2013-08-01

    In bony fish or other aquatic vertebrates, the aryl hydrocarbon receptor (AhR) signaling pathway is initiated by exposure to polycyclic (or/and halogenated) aromatic hydrocarbons (PAHs, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), which subsequently induces the up-regulated expression of a series of related genes (such as cytochrome P4501A (CYP1A)). However, a lack of applicable protein reagents hinders our further understanding of the AhR signaling pathway, which focuses only on gene-based investigations. The goldfish (Carassius auratus) is an ideal model for a study of environmental pollution in whole-Asian fresh water. Here, three sensitive and specific polyclonal antisera against goldfish AhR1, AhR2, and CYP1A proteins were developed. These antisera not only bound the in-vitro synthesized target proteins, but recognized the real proteins expressed in goldfish tissues, with minimal cross-reactivity to non-specific proteins. Together with the analysis of semi-quantitative RT-PCR and polyclonal-antibody-based sandwich ELISA, we confirmed that goldfish AhRs differed in the expression (mRNA and protein levels) patterns among test tissues. Importantly, the relative abundance of each AhR mRNA levels from the different tissues showed no obvious consistency with their protein levels. After exposure to TCDD, goldfish AhR2 showed a more sensitivity than AhR1, and stimulated CYP1A expression directly, similar with the other reported fish models. Overall, development of these antibodies in this study will allow valuable and versatile investigations to further understand the AhR signaling pathway, and different expression (mRNA and protein) patterns represent the first step in determining the regulatory mechanisms underlying the TCDD-exposed aquatic environment.

  18. Beta-naphthoflavone causes an AhR-independent inhibition of invasion and intracellular multiplication of Listeria monocytogenes in murine hepatocytes

    PubMed Central

    Shi, Lewis Zhichang; Czuprynski, Charles J.

    2009-01-01

    We recently reported a heretofore unknown role for the aryl hydrocarbon receptor in host resistance to listeriosis in mice. Hepatocytes are an important site for Listeria monocytogenes multiplication in vivo. In this study, we investigated whether activation of AhR in TIB73 murine embryonic hepatocytes affects the ingestion and intracellular multiplication of L. monocytogenes. Treatment of TIB73 cells with the AhR agonist β-naphthoflavone (BNF) significantly inhibited the ingestion and intracellular growth of L. monocytogenes. The inhibitory effects of BNF were dose-dependent and correlated with up-regulation of CYP1A1. Surprisingly, pretreatment with AhR antagonists (3′-MNF or α-naphthoflavone) or knocking-down of AhR with siRNA did not abolish the inhibitory effects of BNF. Moreover, the inhibitory effects of BNF on invasion and intracellular growth of L. monocytogenes by BNF were observed in AhR-deficient (CRL-2710), or ARNT-dysfunctional (CRL-2717) Hepa cells. We also observed similar inhibitory effects of BNF treatment using primary hepatocytes recovered from AhR+/- or AhR-/- mice. Moreover, the prototypic AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) did not inhibit the invasion and intracellular growth of L. monocytogenes in TIB73 cells. Mechanistic studies demonstrated that ROS, but not TNF-α or iNOS, plays an important role in mediating BNF-induced inhibition. In conclusion, BNF caused an AhR-independent inhibition of ingestion and intracellular multiplication of L. monocytogenes in murine hepatocytes, mediated in part by production of ROS. PMID:19715752

  19. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

    PubMed

    Rondy, M; Castilla, J; Launay, O; Costanzo, S; Ezpeleta, C; Galtier, F; de Gaetano Donati, K; Moren, A

    2016-05-01

    We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. PMID:27065000

  20. 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

  1. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

    PubMed

    Rondy, M; Castilla, J; Launay, O; Costanzo, S; Ezpeleta, C; Galtier, F; de Gaetano Donati, K; Moren, A

    2016-05-01

    We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups.

  2. Response to the 2009 influenza A(H1N1) pandemic in Italy.

    PubMed

    Rizzo, C; Rota, M C; Bella, A; Giannitelli, S; De Santis, S; Nacca, G; Pompa, M G; Vellucci, L; Salmaso, S; Declich, S

    2010-12-01

    In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July – 2 August) of 2009 to week 17 (26 April – 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.

  3. Thermal behavior and electrochemical heat generation in a commercial 40 Ah lithium ion pouch cell

    NASA Astrophysics Data System (ADS)

    Schuster, Elke; Ziebert, Carlos; Melcher, Andreas; Rohde, Magnus; Seifert, Hans Jürgen

    2015-07-01

    Quantitative data on the thermal behavior of lithium ion batteries under charging and discharging conditions are essential for designing thermal management systems and improving battery safety. In this work, commercial 40 Ah lithium ion pouch cells with Li(Ni1/3Mn1/3Co1/3)O2 cathodes were tested under isoperibolic and adiabatic conditions in an Accelerating Rate Calorimeter at different charging/discharging currents from 5 A to 40 A. Adiabatic tests simulate the worst-case scenario of a battery pack without cooling. For charging and discharging an overall exothermic behavior was found and a total temperature increase for one half cycle between 3 and 11 K. Isoperibolic tests simulate a single cell under constant environmental temperature. Here an exothermic behavior for discharging and an endothermic behavior for charging were observed. To transfer the measured temperature changes into heat data, the effective specific heat capacity and the heat transfer coefficient were determined. For the first time the heat generation data for a large format pouch cell have been determined using both isoperibolic and adiabatic conditions. These data were compared with the total heat data calculated as the sum of reversible and irreversible heat that were measured by potentiometric and current interruption techniques respectively. A good agreement was found between all three heat generation determination methods.

  4. The early diversification of influenza A/H1N1pdm

    PubMed Central

    Nelson, Martha; Spiro, David; Wentworth, David; Fan, Jiang; Beck, Eric; St. George, Kirsten; Ghedin, Elodie; Halpin, Rebecca; Bera, Jayati; Hine, Erin; Proudfoot, Kathleen; Stockwell, Tim; Lin, Xudong; Griesemer, Sara; Bose, Michael; Jurgens, Lisa; Kumar, Swati; Viboud, Cecile; Holmes, Edward; Henrickson, Kelly

    2009-01-01

    Background Since its initial detection in April 2009, the A/H1N1pdm influenza virus has spread rapidly in humans, with over 5,700 human deaths. However, little is known about the evolutionary dynamics of H1N1pdm and its geographic and temporal diversification. Methods Phylogenetic analysis was conducted upon the concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates sampled globally between April 1 – July 9, 2009, including relatively large samples from the US states of Wisconsin and New York. Results At least 7 phylogenetically distinct viral clades have disseminated globally and co-circulated in localities that experienced multiple introductions of H1N1pdm. The epidemics in New York and Wisconsin were dominated by two different clades, both phylogenetically distinct from the viruses first identified in California and Mexico, suggesting an important role for founder effects in determining local viral population structures. Conclusions Determining the global diversity of H1N1pdm is central to understanding the evolution and spatial spread of the current pandemic, and to predict its future impact on human populations. Our results indicate that H1N1pdm has already diversified into distinct viral lineages with defined spatial patterns. PMID:20029664

  5. Influenza A(H7N9) Virus Transmission between Finches and Poultry

    PubMed Central

    Jones, Jeremy C.; Sonnberg, Stephanie; Webby, Richard J.

    2015-01-01

    Low pathogenicity avian influenza A(H7N9) virus has been detected in poultry since 2013, and the virus has caused >450 infections in humans. The mode of subtype H7N9 virus transmission between avian species remains largely unknown, but various wild birds have been implicated as a source of transmission. H7N9 virus was recently detected in a wild sparrow in Shanghai, China, and passerine birds, such as finches, which share space and resources with wild migratory birds, poultry, and humans, can be productively infected with the virus. We demonstrate that interspecies transmission of H7N9 virus occurs readily between society finches and bobwhite quail but only sporadically between finches and chickens. Inoculated finches are better able to infect naive poultry than the reverse. Transmission occurs through shared water but not through the airborne route. It is therefore conceivable that passerine birds may serve as vectors for dissemination of H7N9 virus to domestic poultry. PMID:25811839

  6. Antigenic and Molecular Characterization of Avian Influenza A(H9N2) Viruses, Bangladesh

    PubMed Central

    Shanmuganatham, Karthik; Feeroz, Mohammed M.; Jones-Engel, Lisa; Smith, Gavin J.D.; Fourment, Mathieu; Walker, David; McClenaghan, Laura; Alam, S.M. Rabiul; Hasan, M. Kamrul; Seiler, Patrick; Franks, John; Danner, Angie; Barman, Subrata; McKenzie, Pamela; Krauss, Scott; Webby, Richard J.

    2013-01-01

    Human infection with avian influenza A(H9N2) virus was identified in Bangladesh in 2011. Surveillance for influenza viruses in apparently healthy poultry in live-bird markets in Bangladesh during 2008–2011 showed that subtype H9N2 viruses are isolated year-round, whereas highly pathogenic subtype H5N1 viruses are co-isolated with subtype H9N2 primarily during the winter months. Phylogenetic analysis of the subtype H9N2 viruses showed that they are reassortants possessing 3 gene segments related to subtype H7N3; the remaining gene segments were from the subtype H9N2 G1 clade. We detected no reassortment with subtype H5N1 viruses. Serologic analyses of subtype H9N2 viruses from chickens revealed antigenic conservation, whereas analyses of viruses from quail showed antigenic drift. Molecular analysis showed that multiple mammalian-specific mutations have become fixed in the subtype H9N2 viruses, including changes in the hemagglutinin, matrix, and polymerase proteins. Our results indicate that these viruses could mutate to be transmissible from birds to mammals, including humans. PMID:23968540

  7. A thermostable humic acid peroxidase from Streptomyces sp. strain AH4: purification and biochemical characterization.

    PubMed

    Fodil, Djamila; Jaouadi, Bassem; Badis, Abdelmalek; Nadia, Zaraî Jaouadi; Ferradji, Fatma Zohra; Bejar, Samir; Boutoumi, Houcine

    2012-05-01

    An extracellular thermostable humic acid peroxidase (HaP3) was isolated from a Streptomyces sp. strain AH4. MALDI-TOF MS analysis showed that the purified enzyme was a monomer with a molecular mass of 60,215.18Da. The 26N-terminal residues of HaP3 displayed high homology with Streptomyces peroxidases. Optimal peroxidase activity was obtained at pH 5 and 80°C. HaP3 was stable at pH and temperature ranges of 4-8 and 60-90°C for 72 and 4h, respectively. HaP3 catalyzed the oxidation of 2,4-dichlorophenol, commercial humic acid, guiacol, and 2,6-dichlorophenol (50mM); L-3,4-dihydroxyphenylalanine (40 mM); 4-chlorophenol, 2,4,5-trichlorophenol, and 2,4,6-trichlorophenol (30 mM) in the presence of hydrogen peroxide. Sodium azide and potassium cyanide inhibited HaP3, which indicated the presence of heme components. These properties make HaP3 a potential strong candidate for future application in the elimination of natural humic acids in drinking water. PMID:22342039

  8. Influenza A(H1N1)pdm09 during air travel

    PubMed Central

    Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.

    2015-01-01

    Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  9. [Effect of Yinghua Pinggan granule against influenza A/H1N1 virus in vivo].

    PubMed

    Peng, Xue-qian; He, Yu; Zhou, Hui-fen; Zhang, Yu-yan; Yang, Jie-hong; Chen, Jun-kui; Lu, Yi-yu; Wan, Hai-tong

    2015-10-01

    To study the effect of Yinghua Pinggan granule (YHPG) against influenza A/H1N1 virus in vivo and on the immunologic function of infected mice. The intranasal influenza virus infection was adopted in ICR mouse to establish the influenza virus pneumonia model. At the 3rd and 7th day after the infection, the lung index and pathologic changes in lung tissues of mice were detected. Realtime PCR and flow cytometry were employed to observe the virus load in lung tissues and the levels of CD4+, CD8+, and CD4+/CD8+ in peripheral blood. The result showed that at the 3rd and 7th day after the infection, YHPG (15, 30 g x kg(-1)) can significant decrease in the lung index and virus load in lung tissues of mice infected with influenza virus, alleviate the pathologic changes in lung tissues, significantly increase the levels of CD4+ and CD4+/CD8+ ratio and reduce the levels of CD8+ in whole blood. This indicated that YHPG can inhibit the influenza virus replication, alleviate pulmonary damage and adjust the weak immunologic function of infected mice, with a certain therapeutic effect on mice infected by H1N1 virus in vivo.

  10. Influenza A(H7N9) virus transmission between finches and poultry.

    PubMed

    Jones, Jeremy C; Sonnberg, Stephanie; Webby, Richard J; Webster, Robert G

    2015-04-01

    Low pathogenicity avian influenza A(H7N9) virus has been detected in poultry since 2013, and the virus has caused >450 infections in humans. The mode of subtype H7N9 virus transmission between avian species remains largely unknown, but various wild birds have been implicated as a source of transmission. H7N9 virus was recently detected in a wild sparrow in Shanghai, China, and passerine birds, such as finches, which share space and resources with wild migratory birds, poultry, and humans, can be productively infected with the virus. We demonstrate that interspecies transmission of H7N9 virus occurs readily between society finches and bobwhite quail but only sporadically between finches and chickens. Inoculated finches are better able to infect naive poultry than the reverse. Transmission occurs through shared water but not through the airborne route. It is therefore conceivable that passerine birds may serve as vectors for dissemination of H7N9 virus to domestic poultry.

  11. Officimalonic acids A-H, lanostane triterpenes from the fruiting bodies of Fomes officinalis.

    PubMed

    Han, Jianxin; Li, Liya; Zhong, Jialiang; Tohtaton, Zeynep; Ren, Qing; Han, Li; Huang, Xueshi; Yuan, Tao

    2016-10-01

    Phytochemical investigation of the methanolic extract of the fruiting bodies of Fomes officinalis led to the isolation of eight 24-methyl-lanostane triterpenes named officimalonic acids A-H, along with one known lanostane triterpene. Their structures were elucidated based on the analysis of spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism. Officimalonic acid A represents a previously unknown triterpene type with a 24-methyl-7(8 → 9)abeo-lanostane skeleton, and all of the compounds possessed a malonate half-ester moiety at C-3. Anti-inflammatory assay revealed that officimalonic acids D, E, G, H, and fomitopsin A showed potent inhibitory effects (IC50 = 5.1-8.9 μM) on nitric oxide production in lipopolysaccharide-induced RAW264.7 cells. Officimalonic acids E, G, H showed moderate cytotoxicity against H460, HepG2 and BGC-823 human cell lines. PMID:27216472

  12. A thermostable humic acid peroxidase from Streptomyces sp. strain AH4: purification and biochemical characterization.

    PubMed

    Fodil, Djamila; Jaouadi, Bassem; Badis, Abdelmalek; Nadia, Zaraî Jaouadi; Ferradji, Fatma Zohra; Bejar, Samir; Boutoumi, Houcine

    2012-05-01

    An extracellular thermostable humic acid peroxidase (HaP3) was isolated from a Streptomyces sp. strain AH4. MALDI-TOF MS analysis showed that the purified enzyme was a monomer with a molecular mass of 60,215.18Da. The 26N-terminal residues of HaP3 displayed high homology with Streptomyces peroxidases. Optimal peroxidase activity was obtained at pH 5 and 80°C. HaP3 was stable at pH and temperature ranges of 4-8 and 60-90°C for 72 and 4h, respectively. HaP3 catalyzed the oxidation of 2,4-dichlorophenol, commercial humic acid, guiacol, and 2,6-dichlorophenol (50mM); L-3,4-dihydroxyphenylalanine (40 mM); 4-chlorophenol, 2,4,5-trichlorophenol, and 2,4,6-trichlorophenol (30 mM) in the presence of hydrogen peroxide. Sodium azide and potassium cyanide inhibited HaP3, which indicated the presence of heme components. These properties make HaP3 a potential strong candidate for future application in the elimination of natural humic acids in drinking water.

  13. Development of high productivity medium current ion implanter 'EXCEED 3000AH Evo2'

    SciTech Connect

    Ikejiri, T.; Hamamoto, N.; Hisada, S.; Iwasawa, K.; Kawakami, K.; Kokuryu, K.; Miyamoto, N.; Nogami, T.; Sakamoto, T.; Sasada, Y.; Tanaka, K.; Yamamoto, Y.; Yamashita, T.

    2011-01-07

    High productivity medium current ion implanter 'EXCEED 3000AH Evo2' is developed. In semiconductor manufacturing field, improvement of the productivity is continuously required. Especially mass production lines recently tend to use low energy beam and 2 pass implant for higher throughput. The 'Evo2' has been developed in an effort to fulfill these requirements. The 'Evo2' increases low energy beam current by 150 to 250% by applying electrostatic einzel lens called 'V-lens' installed at the exit of the Collimator magnet. This lens is also able to control the beam incident angle by adjusting the upper and lower electrode's voltages independently. Besides, mechanical scanning speed is enhanced to minimize process time of 2 pass implant, while also frequency of the fast beam scanning is enhanced to keep dose uniformity. In addition, a vacuum pumping capability at the target chamber is enhanced to reduce a vacuum waiting time during processing photo-resist wafers. This improvement achieved to reduce process time by 40% for a specific recipe. Furthermore, a modified Indirectly Heated Cathode with electron active Reflection 2 (IHC-R2) ion source which has a long life time filament has been installed. These new elements and/or functions have realized typically 25% improvement of productivity compared to standard EXCEED, and also improve a precise implantation capability.

  14. Influenza A/H1N1_09: Australia and New Zealand's winter of discontent.

    PubMed

    Kotsimbos, Tom; Waterer, Grant; Jenkins, Christine; Kelly, Paul M; Cheng, Allen; Hancox, Robert J; Holmes, Mark; Wood-Baker, Richard; Bowler, Simon; Irving, Louis; Thompson, Philip

    2010-02-15

    Influenza A/H1N1_09 emerged in Mexico at the end of the Northern Hemisphere winter. Within weeks, the focus shifted to the Southern Hemisphere as the introduction of the novel virus coincided with the beginning of the influenza season. Intensive public health and health services planning had occurred in Australia and New Zealand as preparation for an influenza pandemic before 2009. However, this first pandemic wave was quite different to what had been expected. Key elements of the pandemic and response are outlined from the perspective of clinicians working at the frontline of patient care. In particular, they examine why past influenza pandemics and recent history are poor predictors of the current pandemic, the discordance between potential for transmission and disease severity, the broad clinical spectrum of H1N1_09 infection, clinical and health service management issues, and the relationship between health care and government policy. Finally, they address the need for the respiratory community to show leadership in times of crisis. Lessons learned in Australia and New Zealand during 2009 have important messages for similarly resourced countries in the Northern Hemisphere in the coming months as they face their own influenza season.

  15. The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines.

    PubMed

    John, Kaarthik; Lahoti, Tejas S; Wagner, Kelly; Hughes, Jarod M; Perdew, Gary H

    2014-10-01

    Previous studies in head and neck squamous cell carcinoma (HNSCC) cell lines have revealed that the Ah receptor (AHR) plays a significant role in mediating the "aggressive" phenotype of these cells, which includes enhanced inflammatory signaling (e.g., IL6) and migratory potential. Here we sought to identify putative novel targets of the AHR associated with enhanced tumor invasiveness. Global gene expression analysis identified a number of genes that are repressed upon treatment of OSC-19 or HN30 cells with an AHR antagonist. Three growth factors were targets of AHR activity; amphiregulin (AREG), epiregulin (EREG), and platelet-derived growth factor A (PDGFA) were repressed by an AHR antagonist and further examined. Quantitative PCR analysis, ELISA, and siRNA-mediated knock down of AHR revealed an attenuation of basal and/or induced levels of expression of these growth factors in two HNSCC lines, following AHR antagonism. In silico analysis revealed that these growth factors possess dioxin-like response elements. Two other AHR ligands, 6-formylindolo[3,2-b]carbazole and benzo(a)pyrene (BP) also elicited similar responses. In conclusion, this study identified AREG, EREG, and PDGFA as growth factor targets of AHR activity associated with metastatic phenotype of HNSCC cells, suggesting that attenuation of AHR activity may be a therapeutic strategy.

  16. Measured voluntary avoidance behaviour during the 2009 A/H1N1 epidemic

    PubMed Central

    Bayham, Jude; Kuminoff, Nicolai V.; Gunn, Quentin; Fenichel, Eli P.

    2015-01-01

    Managing infectious disease is among the foremost challenges for public health policy. Interpersonal contacts play a critical role in infectious disease transmission, and recent advances in epidemiological theory suggest a central role for adaptive human behaviour with respect to changing contact patterns. However, theoretical studies cannot answer the following question: are individual responses to disease of sufficient magnitude to shape epidemiological dynamics and infectious disease risk? We provide empirical evidence that Americans voluntarily reduced their time spent in public places during the 2009 A/H1N1 swine flu, and that these behavioural shifts were of a magnitude capable of reducing the total number of cases. We simulate 10 years of epidemics (2003–2012) based on mixing patterns derived from individual time-use data to show that the mixing patterns in 2009 yield the lowest number of total infections relative to if the epidemic had occurred in any of the other nine years. The World Health Organization and other public health bodies have emphasized an important role for ‘distancing’ or non-pharmaceutical interventions. Our empirical results suggest that neglect for voluntary avoidance behaviour in epidemic models may overestimate the public health benefits of public social distancing policies. PMID:26511046

  17. The influenza A(H1N1) epidemic in Mexico. Lessons learned

    PubMed Central

    Córdova-Villalobos, José A; Sarti, Elsa; Arzoz-Padrés, Jacqueline; Manuell-Lee, Gabriel; Méndez, Josefina Romero; Kuri-Morales, Pablo

    2009-01-01

    Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health. PMID:19785747

  18. Hippolides A-H, acyclic manoalide derivatives from the marine sponge Hippospongia lachne.

    PubMed

    Piao, Shu-Juan; Zhang, Hong-Jun; Lu, Hai-Yan; Yang, Fan; Jiao, Wei-Hua; Yi, Yang-Hua; Chen, Wan-Sheng; Lin, Hou-Wen

    2011-05-27

    Eight new acyclic manoalide-related sesterterpenes, hippolides A-H (1-8), together with two known manoalide derivatives, (6E)-neomanoalide (9) and (6Z)-neomanoalide (10), were isolated from the South China Sea sponge Hippospongia lachne. The absolute configurations of 1-8 were established by the modified Mosher's method and CD data. Compound 1 exhibited cytotoxicity against A549, HeLa, and HCT-116 cell lines with IC50 values of 5.22×10(-2), 4.80×10(-2), and 9.78 μM, respectively. Compound 1 also showed moderate PTP1B inhibitory activitiy with an IC50 value of 23.81 μM, and compound 2 showed moderate cytotoxicity against the HCT-116 cell line and PTP1B inhibitory activity with IC50 values of 35.13 and 39.67 μM, respectively. In addition, compounds 1 and 5 showed weak anti-inflammatory activity, with IC50 values of 61.97 and 40.35 μM for PKCγ and PKCα, respectively.

  19. Measured voluntary avoidance behaviour during the 2009 A/H1N1 epidemic.

    PubMed

    Bayham, Jude; Kuminoff, Nicolai V; Gunn, Quentin; Fenichel, Eli P

    2015-11-01

    Managing infectious disease is among the foremost challenges for public health policy. Interpersonal contacts play a critical role in infectious disease transmission, and recent advances in epidemiological theory suggest a central role for adaptive human behaviour with respect to changing contact patterns. However, theoretical studies cannot answer the following question: are individual responses to disease of sufficient magnitude to shape epidemiological dynamics and infectious disease risk? We provide empirical evidence that Americans voluntarily reduced their time spent in public places during the 2009 A/H1N1 swine flu, and that these behavioural shifts were of a magnitude capable of reducing the total number of cases. We simulate 10 years of epidemics (2003-2012) based on mixing patterns derived from individual time-use data to show that the mixing patterns in 2009 yield the lowest number of total infections relative to if the epidemic had occurred in any of the other nine years. The World Health Organization and other public health bodies have emphasized an important role for 'distancing' or non-pharmaceutical interventions. Our empirical results suggest that neglect for voluntary avoidance behaviour in epidemic models may overestimate the public health benefits of public social distancing policies. PMID:26511046

  20. Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

    PubMed

    Tsuneki, Akeno; Itagaki, Asao; Tsuchie, Hideaki; Tokuhara, Misato; Okada, Takayoshi; Narai, Sakae; Kasagi, Masaaki; Tanaka, Kiyoshi; Kageyama, Seiji

    2013-11-01

    A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

  1. Behavioral Rhythmicity of Mice Lacking AhR and Attenuation of Light-induced Phase Shift by 2,3,7,8-Tetracholordibenzo-p-dioxin

    PubMed Central

    Mukai, Motoko; Lin, Tien-Min; Peterson, Richard E.; Cooke, Paul S.; Tischkau, Shelley A.

    2008-01-01

    Transcription factors belonging to the Per/Arnt/Sim (PAS) domain family are highly conserved and many are involved in circadian rhythm regulation. One member of this family, aryl hydrocarbon receptor (AhR), is an orphan receptor whose physiological role is unknown. Recent findings have led to the hypothesis that AhR has a role in circadian rhythm, which is the focus of the present investigation. First, time-of-day dependent mRNA expression of AhR and its signaling target, cytochrome p4501A1 (Cyp1a1) was determined in C57BL/6J mice by quantitative RT-PCR. Circadian expression of AhR and Cyp1a1 was observed both in the suprachiasmatic nucleus (SCN) and liver. Next, the circadian phenotype of mice lacking AhR (AhRKO) was investigated using behavioral monitoring. Intact AhRKO mice had robust circadian rhythmicity with a similar tau under constant conditions compared to wild-type mice, but a significant difference in tau was observed between genotypes in ovariectomized female mice. Time to re-entrainment following 6-h advances or delays of the light/dark cycle was not significantly different between genotypes. However, mice exposed to the AhR agonist 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD, 1 μg/kg BW) displayed decreased phase shifts in response to light and had altered expression of Per1 and Bmal1. These results suggest that chronic activation of AhR may affect the ability of the circadian timekeeping system to adjust to alterations in environmental lighting by affecting canonical clock genes. Further studies are necessary to decipher the mechanism of how AhR agonists could disrupt light-induced phase shifts. If AhR does have a role in circadian rhythm, it may share redundant roles with other PAS domain proteins and/or the role of AhR may not be exhibited in the behavioral activity rhythm, but could be important elsewhere in the peripheral circadian system. PMID:18487412

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

    PubMed

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

    2014-02-01

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

  3. The effects of oral AH 5158, a combined α and β-adrenoceptor antagonist, in healthy volunteers

    PubMed Central

    Richards, D. A.; Woodings, E. P.; Stephens, M. D. B.; Maconochie, J. G.

    1974-01-01

    1 In healthy male volunteers after single oral doses, AH 5158 produced inhibition of exercise induced tachycardia, falls in systolic and diastolic pressure at rest and in response to exercise, which are probably related to combined β- and α-adrenoceptor antagonism. 2 At increasing doses from 100 mg to 400 mg there exists a dose related antagonistic effect, though the dominant effect of β-adrenoceptor antagonism is more easily demonstrable than is α antagonism. 3 As indicated by the pattern of pharmacological effects, absorption of the oral drug is good and the duration of action of a 400 mg dose is approximately 8 hours. 4 Despite being administered in β-adrenoceptor blocking doses, AH 5158 had no adverse effects upon peak expiratory flow at rest or in response to exercise. 5 It is concluded that the pharmacological profile of this combined α- and β-adrenoceptor antagonism suggests a potential therapeutic role as an antihypertensive drug. PMID:22454938

  4. Field assessment of Bt cry1Ah corn pollen on the survival, development and behavior of Apis mellifera ligustica.

    PubMed

    Dai, Ping-Li; Zhou, Wei; Zhang, Jie; Cui, Hong-Juan; Wang, Qiang; Jiang, Wei-Yu; Sun, Ji-Hu; Wu, Yan-Yan; Zhou, Ting

    2012-05-01

    Honeybees may be exposed to insecticidal proteins from transgenic plants via pollen. An assessment of the impact of such exposures on the honeybee is an essential part of the risk assessment process for transgenic Bacillus thuringiensis corn. A field trial was conducted to evaluate the effect of transgenic Bt cry1Ah corn on the honeybee Apis mellifera ligustica. Colonies of honeybees were moved to Bt or non-Bt corn fields during anthesis and then sampled to record their survival, development and behavior. No differences in immature stages, worker survival, bee body weight, hypopharyngeal gland weight, colony performance, foraging activity or olfactory learning abilities were detected between colonies that were placed in non-Bt corn fields and those placed in Bt corn fields. We conclude that cry1Ah corn carries no risk for the survival, development, colony performance or behavior of the honeybee A. mellifera ligustica. PMID:22364780

  5. 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

  6. 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

  7. 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

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

    PubMed

    Gao, Zhan; Bu, Yongjun; Liu, Xiaozhuan; Wang, Xugang; Zhang, Guofu; Wang, Erhui; Ding, Shibin; Liu, Yongfeng; Shi, Ruling; Li, Qiaoyun; Fu, Jianhong; Yu, Zengli

    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 cell 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. PMID:26971374

  9. The assessment of the AH-64D, longbow, mast-mounted assembly noise hazard for maintenance personnel

    NASA Astrophysics Data System (ADS)

    Mozo, Ben T.; Gordon, Elmaree

    1994-07-01

    Noise levels around the AH-64 helicopter exceed safe limits. Maintenance personnel are required to wear hearing protection to reduce hazard to hearing while performing maintenance procedures. This evaluation was directed at determining the contribution to noise levels by the auxiliary power unit (APU), auxiliary ground power unit (AGPU), environmental control system (ECS), and mast mounted assembly (MMA) at a variety of maintenance positions and establish protection capabilities of standard protectors for those noise levels.

  10. 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.

  11. Avian Influenza A(H7N9) Virus Infection in 2 Travelers Returning from China to Canada, January 20151

    PubMed Central

    Chambers, Catharine; Gustafson, Reka; Purych, Dale B.; Tang, Patrick; Bastien, Nathalie; Krajden, Mel; Li, Yan

    2016-01-01

    In January 2015, British Columbia, Canada, reported avian influenza A(H7N9) virus infection in 2 travelers returning from China who sought outpatient care for typical influenza-like illness. There was no further spread, but serosurvey findings showed broad population susceptibility to H7N9 virus. Travel history and timely notification are critical to emerging pathogen detection and response. PMID:26689320

  12. 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

    A 12 Ah Nickel-Cadmium (NiCd) Low Earth Orbit (LEO) life cycle test that induced 47 percent more deep Depth Of Discharge cycles by mixing them with shallow DOD cycles is discussed. The test showed how aggressive recharging to a C/D ratio of 1.15 nearly doubled performance over cycling below a C/D of 1.11.

  13. Prospective cohort study of the safety of an influenza A(H1N1) vaccine in pregnant Chinese women.

    PubMed

    Ma, Fubao; Zhang, Longhua; Jiang, Renjie; Zhang, Jinlin; Wang, Huaqing; Gao, Xiaozhi; Li, Xiuhong; Liu, Yuanbao

    2014-09-01

    To monitor and evaluate the safety of the influenza A(H1N1) vaccine in pregnant women and its influence on the fetus and neonate, we performed a prospective study in which 122 pregnant Chinese women who received the influenza A(H1N1) vaccine and 104 pregnant women who did not receive any vaccine (serving as controls) were observed. The results indicated that the seroconversion rate in the vaccinated group was 90.4% (95% confidence interval [CI], 82.6% to 95.5%). The rate of adverse events following immunization in the pregnant women who received the influenza A(H1N1) vaccine was 3.3%. The spontaneous abortion rates in the vaccinated group and the unvaccinated group were 0.8% and 1.9%, respectively (exact probability test, P = 0.470), the prolonged-pregnancy rates were 8.2% and 4.8%, respectively (χ(2) = 1.041, P = 0.308), the low-birth-weight rates were 1.6% and 0.95%, respectively (exact probability test, P = 1.000), and the spontaneous-labor rates were 70.5% and 75%, respectively (χ(2) = 0.573, P = 0.449). All newborns who have an Apgar score of ≥7 are considered healthy; Apgar scores of ≥9 were observed in 38.5% and 57.7% of newborns in the vaccinated group and the unvaccinated group, respectively (χ(2) = 8.274, P = 0.004). From these results, we conclude that the influenza A(H1N1) vaccine is safe for pregnant women and has no observed adverse effects on fetal growth. (This study has been registered at ClinicalTrials.gov under registration no. NCT01842997.).

  14. 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. PMID:27598244

  15. Calorimetric Measurements on a 32 Ah Li/MnO2 Cell for the X-38 Crew Return Vehicle

    NASA Technical Reports Server (NTRS)

    Darcy, Eric; Johnson, Chris

    2000-01-01

    A viewgraph presentation outlines the batteries used for the X-38 crew return vehicle. Three battery systems are described: the 350 Ah Li/MnO2 battery module, the Li/MnO2 cell battery, and the battery string of 12 cells. First thermal vacuum test results are shown, and improvements for the battery thermal design are discussed. Preliminary findings for tests and future work are described.

  16. 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

  17. Root canal filling in primary molars without successors: Mineral trioxide aggregate versus gutta-percha/AH-Plus.

    PubMed

    Bezgin, Tugba; Ozgul, Betul Memiş; Arikan, Volkan; Sari, Saziye

    2016-08-01

    The aim of this study was to compare the clinical and radiographical success of mineral trioxide aggregate (MTA) and gutta-percha/AH-Plus used as a root canal filling material in primary second molars without successors. A total of 16 patients (9 girls, 7 boys) aged 6-13 years (mean: 10.5) were selected and randomly distributed into the treatment groups. Children were recalled for clinical and radiographic examination at 6, 12, 18, 24 and 36 months. Differences in treatment outcomes were analysed using chi-squared and Fisher's exact tests. Clinically, there was no significant difference in the success rates between the groups at the end of a 3-year follow-up period (MTA: 100%; Gutta-percha/AH-Plus: 70%) (P > 0.05). However, radiographically, there was a significant difference between the groups (MTA: 80%; gutta-percha/AH-Plus: 30%) (P < 0.05). The present study showed that MTA can be recommended for use in root canal treatment of primary molars without successors based on better radiographic success.

  18. 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

  19. Molecular Analysis of Three Aeromonas hydrophila AH-3 (Serotype O34) Lipopolysaccharide Core Biosynthesis Gene Clusters▿ †

    PubMed Central

    Jimenez, Natalia; Canals, Rocío; Lacasta, Anna; Kondakova, Anna N.; Lindner, Buko; Knirel, Yuriy A.; Merino, Susana; Regué, Miguel; Tomás, Juan M.

    2008-01-01

    By the isolation of three different Aeromonas hydrophila strain AH-3 (serotype O34) mutants with an altered lipopolysaccharide (LPS) migration in gels, three genomic regions encompassing LPS core biosynthesis genes were identified and characterized. When possible, mutants were constructed using each gene from the three regions, containing seven, four, and two genes (regions 1 to 3, respectively). The mutant LPS core structures were elucidated by using mass spectrometry, methylation analysis, and comparison with the full core structure of an O-antigen-lacking AH-3 mutant previously established by us. Combining the gene sequence and complementation test data with the structural data and phenotypic characterization of the mutant LPSs enabled a presumptive assignment of all LPS core biosynthesis gene functions in A. hydrophila AH-3. The three regions and the genes contained are in complete agreement with the recently sequenced genome of A. hydrophila ATCC 7966. The functions of the A. hydrophila genes waaC in region 3 and waaF in region 2 were completely established, allowing the genome annotations of the two heptosyl transferase products not previously assigned. Having the functions of all genes involved with the LPS core biosynthesis and most corresponding single-gene mutants now allows experimental work on the role of the LPS core in the virulence of A. hydrophila. PMID:18310345

  20. 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

  1. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza. PMID:2066386

  2. Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China

    PubMed Central

    Wang, Liping; Cowling, Benjamin J.; Wu, Peng; Yu, Jianxing; Li, Fu; Zeng, Lingjia; Wu, Joseph T.; Li, Zhongjie; Leung, Gabriel M.

    2014-01-01

    To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses. PMID:25076186

  3. Cardiac Ca(2+) channel-blocking effects of the cyproheptadine derivative AH-1058 in isolated guinea pig cardiomyocytes.

    PubMed

    Dohmoto, Hideki; Takahara, Akira; Uneyama, Hisayuki; Yoshimoto, Ryota

    2003-02-01

    The Ca(2+) channel-blocking efficacy of the cyproheptadine derivative AH-1058 (4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride) was quantitatively assessed using isolated guinea pig cardiomyocytes. AH-1058 (0.001 - 10 microM) and its mother compound cyproheptadine (1 - 100 microM) reduced the Ca(2+) currents elicited from the holding potential of -80 or -40 mV. The IC(50) values for cyproheptadine at holding potentials of -80 and -40 mV were 42.44 and 7.75 microM, respectively, whereas those for AH-1058 were 4.91 and 0.32 microM, respectively, whose potency was equivalent to those of the typical Ca(2+) channel blocker verapamil. These results suggest that the introduction of the cinnamil structure to cyproheptadine can generate a potent L-type Ca(2+) channel-blocking compound as potent as verapamil.

  4. Human exposure to live poultry and psychological and behavioral responses to influenza A(H7N9), China.

    PubMed

    Wang, Liping; Cowling, Benjamin J; Wu, Peng; Yu, Jianxing; Li, Fu; Zeng, Lingjia; Wu, Joseph T; Li, Zhongjie; Leung, Gabriel M; Yu, Hongjie

    2014-08-01

    To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market > or =1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.

  5. Social capital and immunization against the 2009 A(H1N1) pandemic in the American States.

    PubMed

    Rönnerstrand, B

    2014-08-01

    The objective of this paper was to investigate the association between contextual social capital and immunization coverage rates. A cross-sectional, ecologic study design was used. Three different estimations of contextual social capital in American states have been used. Data on immunization coverage rates at state level comes from Centers for Disease Control and Prevention. Correlation coefficients were calculated to investigate the bivariate association between the independent variable social capital and the dependent variable 2009 A(H1N1) immunization coverage rates. A multivariate OLS regression model was used to investigate the association between contextual social capital and immunization, under control for state-level health care spending per capita, state population, population per square mile, and median age in the American States. Results show that Social capital was strongly correlated with 2009 A(H1N1) immunization acceptance among American States. In a multivariate regression analysis, the association remains strong and significant also when controlling state-level confounders. In conclusion, social capital, at least in a U.S. context, is shown to be associated with the state-level uptake of vaccination against the 2009 A(H1N1) pandemic.

  6. 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

  7. Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

    PubMed Central

    Wan, Hongquan; Yang, Hua; Shore, David A.; Garten, Rebecca J.; Couzens, Laura; Gao, Jin; Jiang, Lianlian; Carney, Paul J.; Villanueva, Julie; Stevens, James; Eichelberger, Maryna C.

    2015-01-01

    A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses. PMID:25668439

  8. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza.

  9. The new pandemic influenza A/(H1N1)pdm09 virus: is it really "new"?

    PubMed

    Baldo, V; Bertoncello, C; Cocchio, S; Fonzo, M; Pillon, P; Buja, A; Baldovin, T

    2016-01-01

    In June 2009, the World Health Organization (WHO) issued a pandemic alert concerning the spread of an influenza A (H1N1) virus that showed distinctive genetic characteristics vis-à-vis both seasonal influenza strains and vaccine strains. The main mutation occurred in the gene coding for hemagglutinin (HA). Mathematical models were developed to calculate the transmissibility of the virus; the results indicated a significant overlap with the transmissibility of previous pandemic strains and seasonal strains. The remarkable feature of A/(H1N1)pdm09, compared with seasonal strains, is its high fatality rate and its higher incidence among younger people. Data provided by the WHO on the number of deaths caused by A/(H1N1)pdm09 only include laboratory-confirmed cases. Some authors suggest that these data could underestimate the magnitude of the event, as laboratory confirmation is not obtained in all cases. It is important to bear in mind that the A/(H1N1)pdm09 virus is still circulating in the population. It is therefore essential to maintain its epidemiological and virological surveillance. PMID:27346935

  10. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection.

  11. Willingness of future A/H7N9 influenza vaccine uptake: A cross-sectional study of Hong Kong community.

    PubMed

    Chan, Emily Ying-Yang; Cheng, Calvin Ka-Yeung; Tam, Greta Chun-Huen; Huang, Zhe; Lee, Po Yi

    2015-09-11

    We conducted a population telephone survey in Hong Kong during the second wave of influenza A/H7N9 outbreak in 2014. Among the respondents, 50.5% of the respondents would like to accept A/H7N9 vaccination in future. Respondents had poor knowledge of A/H7N9 influenza and vaccines. More than 60% of respondents mixed up seasonal influenza this year and A/H7N9 influenza. Results show that socio-demographic factors were all independent of the vaccine uptake willingness while anxiety level and vaccine history were the main affecting factors. Vaccine promotion strategies may focus on influenza knowledge, attitude and behavior.

  12. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

    PubMed

    Chambers, Catharine; Skowronski, Danuta M; Sabaiduc, Suzana; Winter, Anne Luise; Dickinson, James A; De Serres, Gaston; Gubbay, Jonathan B; Drews, Steven J; Martineau, Christine; Eshaghi, Alireza; Krajden, Mel; Bastien, Nathalie; Li, Yan

    2016-01-01

    Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

  13. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    PubMed

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection. PMID:25022686

  14. Precursor systems analyses of automated highway systems. Carrier phase GPS for AHS vehicle control. Resource materials. Final report, September 1993-November 1994

    SciTech Connect

    Galijan, R.C.

    1996-01-01

    This report describs the results of a PSA contract awarded to SRI International to analyze applications of advanced Global Positioning System (GPS) measurement techniques to provide data for lateral and longitudinal control of AHS vehicles. The report includes: (1) a review of control sensor requirements suggested by other PSA contractors and AHS researchers; (2) an indepth discussion of GPS principles of operation, advanced techniques for achieving extremely accurate GPS positioning and velocity data, and techniques for augmenting GPS to provide continuous high-accuracy data; (3) current and expected GPS capabilities and performance; (4) a review of other proposed sensor types for providing lateral and longitudinal control data; (5) a description of a notional architecture and operation of an AHS incorporating GPS; and (6) a preliminary evaluation by SRI of GPS operation in a typical AHS roadway environment.

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

    SciTech Connect

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

    2012-09-15

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

  16. Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Uganda

    PubMed Central

    Byarugaba, Denis K.; Ducatez, Mariette F.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Kaira, Blanche B.; Mimbe, Derrick; Schnabel, David C.; Krauss, Scott; Darnell, Daniel; Webby, Richard J.; Webster, Robert G.; Wabwire-Mangen, Fred

    2011-01-01

    The increasing availability of complete influenza virus genomes is deepening our understanding of influenza evolutionary dynamics and facilitating the selection of vaccine strains. However, only one complete African influenza virus sequence is available in the public domain. Here we present a complete genome analysis of 59 influenza A/H3N2 viruses isolated from humans in Uganda during the 2008 and 2009 season. Isolates were recovered from hospital-based sentinel surveillance for influenza-like illnesses and their whole genome sequenced. The viruses circulating during these two seasons clearly differed from each other phylogenetically. They showed a slow evolution away from the 2009/10 recommended vaccine strain (A/Brisbane/10/07), instead clustering with the 2010/11 recommended vaccine strain (A/Perth/16/09) in the A/Victoria/208/09 clade, as observed in other global regions. All of the isolates carried the adamantane resistance marker S31N in the M2 gene and carried several markers of enhanced transmission; as expected, none carried any marker of neuraminidase inhibitor resistance. The hemagglutinin gene of the 2009 isolates differed from that of the 2008 isolates in antigenic sites A, B, D, and to a lesser extent, C and E indicating evidence of an early phylogenetic shift from the 2008 to 2009 viruses. The internal genes of the 2009 isolates were similar to those of one 2008 isolate, A/Uganda/MUWRP-050/2008. Another 2008 isolate had a truncated PB1-F2 protein. Whole genome sequencing can enhance surveillance of future seasonal changes in the viral genome which is crucial to ensure that selected vaccine strains are protective against the strains circulating in Eastern Africa. This data provides an important baseline for this surveillance. Overall the influenza virus activity in Uganda appears to mirror that observed in other regions of the southern hemisphere. PMID:22132146

  17. The challenges of global case reporting during pandemic A(H1N1) 2009.

    PubMed

    Williams, Stephanie; Fitzner, Julia; Merianos, Angela; Mounts, Anthony

    2014-01-01

    During the 2009 A(H1N1) influenza pandemic, the World Health Organization (WHO) asked all Member States to provide case-based data on at least the first 100 laboratory-confirmed influenza cases to generate an early understanding of the pandemic and provide appropriate guidance to affected countries. In reviewing the pandemic surveillance strategy, we evaluated the utility of case-based data collection and the challenges in interpreting these data at the global level. To do this, we assessed compliance with the surveillance recommendation and data completeness of submitted case records and described the epidemiological characteristics of up to the first 110 reported cases from each country, aggregated into regions. From April 2009 to August 2011, WHO received over 18 000 case records from 84 countries. Data reached WHO at different time intervals, in different formats and without information on collection methods. Just over half of the 18 000 records gave the date of symptom onset, which made it difficult to assess whether the cases were among the earliest to be confirmed. Descriptive epidemiological analyses were limited to summarizing age, sex and hospitalization ratios. Centralized analysis of case-based data had little value in describing key features of the pandemic. Results were difficult to interpret and would have been misleading if viewed in isolation. A better approach would be to identify critical questions, standardize data elements and methods of investigation, and create efficient channels for communication between countries and the international public health community. Regular exchange of routine surveillance data will help to consolidate these essential channels of communication.

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

    PubMed Central

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

    2015-01-01

    Background: 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. Objectives: This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Patients and Methods: 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. Results: 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. Conclusions: A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir. PMID:26464773

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

    PubMed

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

    2015-11-01

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

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

    SciTech Connect

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

    2006-04-15

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

  1. Prevalence, genetic drift of haemagglutinin, and antiviral resistance of influenza A/H3N2 viruses circulating in Shanghai in children during 2009-2012.

    PubMed

    Cai, Jiehao; Wang, Xiangshi; Zhao, Baihui; Yao, Weilei; Wang, Xiaohong; Zhu, Qirong; Zeng, Mei

    2014-06-01

    Influenza A/H3N2 viruses are associated with severe epidemics. Antiviral resistance and continued antigenic drift are the major concerns regarding prophylaxis and treatment of influenza. The objectives of this study were to investigate the prevalence and frequency of antiviral drug resistance in influenza A/H3N2 viruses circulating among Shanghainese children from June 2009 to May 2012 and to understand the genetic evolution of the hemagglutinin (HA) epitopes. Nasopharyngeal/throat swabs were collected from outpatients with influenza-like illness. Of the 3,475 children tested, 344 (9.9%) were positive for influenza A/H3N2 viruses. Epidemics of influenza A/H3N2 occurred in July-September 2009, August 2010-January 2011, and November 2011-May 2012. The 71 A/H3N2-positive specimens were sequenced to characterize the genotypic antiviral resistance and genetic drift in the HA epitopes. All of the 71 A/H3N2 viruses sequenced were genotypically resistant to adamantine but sensitive to oseltamivir. The HA1 sequence analysis revealed that the A/H3N2 viruses underwent constant mutations in the HA antigenic sites over the three seasons compared with the corresponding vaccine strains, and amino acid changes in at least three epitopes were observed each season. Phylogenic analyses indicated that the A/H3N2 strains circulating in Shanghai fell into clades different from those of the corresponding seasonal vaccine strains and were grouped into the A/Perth/16/2009 genetic clade and the A/Victoria/208/2009 genetic clades 3B, 3C, and 5. The continuous monitoring of genetic drift and antiviral resistance of influenza viruses is important for the management of influenza and for updating the vaccine composition.

  2. A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June-July 2009.

    PubMed

    de Silva, U C; Warachit, J; Waicharoen, S; Chittaganpitch, M

    2009-08-01

    As the influenza A(H1N1)v pandemic unfolds globally, it is vital to monitor closely for signals of change in the current patterns of transmission. We estimate the basic reproduction ratio for A(H1N1)v virus in Thailand and propose a method to keep track of the actual case count notwithstanding the exponential growth rate. PMID:19660247

  3. Crystal structure and activating effect on RyRs of AhV_TL-I, a glycosylated thrombin-like enzyme from Agkistrodon halys snake venom.

    PubMed

    Zeng, Fuxing; Shen, Bing; Zhu, Zhongliang; Zhang, Ping; Ji, Yonghua; Niu, Liwen; Li, Xu; Teng, Maikun

    2013-03-01

    A snake venom thrombin-like enzyme (SVTLE) from Agkistrodon halys pallas venom was isolated by means of a two-step chromatographic procedure. The purified enzyme, named AhV_TL-I, showed fibrinogenolytic activity against both the Aα and Bβ chains of bovine fibrinogen. Unlike the other SVTLEs, AhV_TL-I has poor esterolytic activity upon BAEE substrate. The N-terminal sequence of AhV_TL-I was determined to be IIGGDEXNINEHRFLVALYT, and the molecular mass was confirmed to 29389.533 Da by MALDI-TOF mass spectrometry. Its complete cDNA and derived amino acid sequence were obtained by RT-PCR. The crystal structure of AhV_TL-I was determined at a resolution of 1.75 Å. A disaccharide was clearly mapped in the structure, which involved in regulating the esterolytic activity of AhV_TL-I. The presence of the N-glycan deformed the 99-loop, and the resulting steric hindrances hindered the substrates to access the active site. Furthermore, with the carbohydrate moiety, AhV_TL-I could induce mouse thoracic aortic ring contraction with the EC(50) of 147 nmol/L. Besides, the vasoconstrictor effects of AhV_TL-I were also independent of the enzymatic activity. The results of [Ca(2+)](i) measurement showed that the vasoconstrictor effects of AhV_TL-I were attributed to Ca(2+) releasing from Ca(2+) store. Further studies showed that it was related to the activation of ryanodine receptors (RyRs). These offer new insights into the snake SVTLEs functions and provide a novel pathogenesis of A. halys pallas venom. PMID:23052203

  4. Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus

    PubMed Central

    Chen, Xu; D'Arcy, Sheena; Radebaugh, Catherine A.; Krzizike, Daniel D.; Giebler, Holli A.; Huang, Liangquan; Nyborg, Jennifer K.; Luger, Karolin

    2016-01-01

    Histone chaperones, like nucleosome assembly protein 1 (Nap1), play a critical role in the maintenance of chromatin architecture. Here, we use the GAL locus in Saccharomyces cerevisiae to investigate the influence of Nap1 on chromatin structure and histone dynamics during distinct transcriptional states. When the GAL locus is not expressed, cells lacking Nap1 show an accumulation of histone H2A-H2B but not histone H3-H4 at this locus. Excess H2A-H2B interacts with the linker DNA between nucleosomes, and the interaction is independent of the inherent DNA-binding affinity of H2A-H2B for these particular sequences as measured in vitro. When the GAL locus is transcribed, excess H2A-H2B is reversed, and levels of all chromatin-bound histones are depleted in cells lacking Nap1. We developed an in vivo system to measure histone exchange at the GAL locus and observed considerable variability in the rate of exchange across the locus in wild-type cells. We recapitulate this variability with in vitro nucleosome reconstitutions, which suggests a contribution of DNA sequence to histone dynamics. We also find that Nap1 is required for transcription-dependent H2A-H2B exchange. Altogether, these results indicate that Nap1 is essential for maintaining proper chromatin composition and modulating the exchange of H2A-H2B in vivo. PMID:26884462

  5. Ultraviolet light converts propranolol, a nonselective β-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand.

    PubMed

    Dorgham, Karim; Amoura, Zahir; Parizot, Christophe; Arnaud, Laurent; Frances, Camille; Pionneau, Cédric; Devilliers, Hervé; Pinto, Sandra; Zoorob, Rima; Miyara, Makoto; Larsen, Martin; Yssel, Hans; Gorochov, Guy; Mathian, Alexis

    2015-11-01

    UV light and some medications are known to trigger lupus erythematosus (LE). A common mechanism underlying the immunopathologic effect, resulting from exposure to these two seemingly unrelated factors, remains unknown. The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of IL-22 production in humans and can be activated by both xenobiotics and naturally occurring photoproducts. A significant expansion of Th17 and Th22 cells was observed in the peripheral blood of active systemic LE (SLE) patients, compared to inactive patients and controls. We also show that propranolol, a potential lupus-inducing drug, induced stronger AhR activation in PBMCs of SLE patients than in those of controls. AhR agonist activity of propranolol was enhanced by UV light exposure. MS analysis of irradiated propranolol revealed the generation of a proinflammatory photoproduct. This compound behaves like the prototypic AhR ligand 6-formylindolo[3,2-b]carbazole, a cutaneous UV light-induced tryptophan metabolite, both promoting IL-22, IL-8, and CCL2 secretion by T-cells and macrophages. Finally, LE patients exhibit signs of cutaneous AhR activation that correlate with lesional expression of the same proinflammatory cytokines, suggesting a role for photometabolites in the induction of skin inflammation. The AhR might therefore represent a target for therapeutic intervention in LE. PMID:26354876

  6. Chaperone Nap1 shields histone surfaces used in a nucleosome and can put H2A-H2B in an unconventional tetrameric form.

    PubMed

    D'Arcy, Sheena; Martin, Kyle W; Panchenko, Tanya; Chen, Xu; Bergeron, Serge; Stargell, Laurie A; Black, Ben E; Luger, Karolin

    2013-09-12

    The histone H2A-H2B heterodimer is an integral component of the nucleosome. The cellular localization and deposition of H2A-H2B into chromatin is regulated by numerous factors, including histone chaperones such as nucleosome assembly protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic strength, the α helices in H2A-H2B are frequently sampling partially disordered conformations and that binding to Nap1 reduces this conformational sampling. We identify the interaction surface between H2A-H2B and Nap1 and confirm its relevance both in vitro and in vivo. We show that two copies of H2A-H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains similar to those in the four-helix bundle structural motif. The organization of the complex reveals that Nap1 competes with histone-DNA and interhistone interactions observed in the nucleosome, thereby regulating the availability of histones for chromatin assembly. PMID:23973327

  7. Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus.

    PubMed

    Chen, Xu; D'Arcy, Sheena; Radebaugh, Catherine A; Krzizike, Daniel D; Giebler, Holli A; Huang, Liangquan; Nyborg, Jennifer K; Luger, Karolin; Stargell, Laurie A

    2016-04-01

    Histone chaperones, like nucleosome assembly protein 1 (Nap1), play a critical role in the maintenance of chromatin architecture. Here, we use the GAL locus in Saccharomyces cerevisiae to investigate the influence of Nap1 on chromatin structure and histone dynamics during distinct transcriptional states. When the GAL locus is not expressed, cells lacking Nap1 show an accumulation of histone H2A-H2B but not histone H3-H4 at this locus. Excess H2A-H2B interacts with the linker DNA between nucleosomes, and the interaction is independent of the inherent DNA-binding affinity of H2A-H2B for these particular sequences as measured in vitro When the GAL locus is transcribed, excess H2A-H2B is reversed, and levels of all chromatin-bound histones are depleted in cells lacking Nap1. We developed an in vivo system to measure histone exchange at the GAL locus and observed considerable variability in the rate of exchange across the locus in wild-type cells. We recapitulate this variability with in vitro nucleosome reconstitutions, which suggests a contribution of DNA sequence to histone dynamics. We also find that Nap1 is required for transcription-dependent H2A-H2B exchange. Altogether, these results indicate that Nap1 is essential for maintaining proper chromatin composition and modulating the exchange of H2A-H2B in vivo. PMID:26884462

  8. Chaperone Nap1 shields histone surfaces used in a nucleosome and can put H2A-H2B in an unconventional tetrameric form

    PubMed Central

    D’Arcy, Sheena; Martin, Kyle W.; Panchenko, Tanya; Chen, Xu; Bergeron, Serge; Stargell, Laurie A.; Black, Ben E.; Luger, Karolin

    2013-01-01

    Summary The histone H2A-H2B heterodimer is an integral component of the nucleosome. The cellular localization and deposition of H2A-H2B into chromatin is regulated by numerous factors including histone chaperones such as Nucleosome Assembly Protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic strength the α-helices in H2A-H2B are frequently sampling partially disordered conformations, and that binding to Nap1 reduces this conformational sampling. We identify the interaction surface between H2A-H2B and Nap1, and confirm its relevance both in vitro and in vivo. We show that two copies of H2A-H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains similar to those in the four-helix bundle structural motif. The organization of the complex reveals that Nap1 competes with histone-DNA and inter-histone interactions observed in the nucleosome, thereby regulating the availability of histones for chromatin assembly. PMID:23973327

  9. Precursor systems analyses of automated highway systems. Knowledge based systems and learning methods for AHS. Volume 10. Final report, September 1993-February 1995

    SciTech Connect

    Schmoltz, J.; Blumer, A.; Noonan, J.; Shedd, D.; Twarog, J.

    1995-06-01

    Managing each AHS vehicle and the AHS system as a whole is an extremely complex yndertaking. The authors have investigated and now report on Artificial Intelligence (AI) approaches that can help. In particular, we focus on AI technologies known as Knowledge Based Systems (KBSs) and Learning Methods (LMs). Our primary purpose is to identify opportunities: we identify several problems in AHS and AI technologies that can solve them. Our secondary purpose is to examine in some detail a subset of these opportunities: we examine how KBSs and LMs can help in controlling the high level movements--e.g., keep in lane, change lanes, speed up, slow down--of an automated vehicle. This detailed examination includes the implementation of a prototype system having three primary components. The Tufts Automated Highway System Kit(TAHSK) discrete time micro-level traffic simulator is a generic AHS simulator. TAHSK interfaces with the Knowledge Based Controller (KBCon) knowledge based high level controller, which controls the high level actions of individual AHS vehicles. Finally, TAHSK also interfaces with a Reinforcement learning (RL) module that was used to explore the possibilities of RL techniques in an AHS environment.

  10. Developing a qPCR method to quantify AhR-PCP-DNA complex for detection of environmental trace-level PCP.

    PubMed

    Zhao, Xiaoxiang; Pang, Xiaoqian; Chaisuwan, Nuanapa

    2011-07-01

    Pentachlorophenol (PCP), a widely-used aseptic or biocide, is known as an environmental toxicant involved in endocrine disruption even at a trace level. In order to reliably and efficiently quantify environmental trace-quantity PCP, this study developed a novel PCP detection method using the aryl hydrocarbon receptor (AhR) and fluorescence quantitative PCR (qPCR). DNA probe with AhR binding sites was synthesized by PCR before added into AhR-PCP complex. After AhR-PCP-DNA complex was digested with exonuclease, copy number of DNA probe was determined using fluorescence qPCR. To calculate PCP concentration in samples, a standard curve (PCP concentration versus Ct value) was constructed and the detection range was 10(-13) to 10(-9) M. PCP detection limit was 0.0089 ppt for the AhR-PCP-DNA complex assay and 8.8780 ppm for high performance liquid chromatography, demonstrating that the method developed in this study is more sensitive. These results suggest that AhR-PCP-DNA complex method may be successfully applicable in detection and quantification of environmental trace-level PCP. PMID:21503612

  11. Ultraviolet light converts propranolol, a nonselective β-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand.

    PubMed

    Dorgham, Karim; Amoura, Zahir; Parizot, Christophe; Arnaud, Laurent; Frances, Camille; Pionneau, Cédric; Devilliers, Hervé; Pinto, Sandra; Zoorob, Rima; Miyara, Makoto; Larsen, Martin; Yssel, Hans; Gorochov, Guy; Mathian, Alexis

    2015-11-01

    UV light and some medications are known to trigger lupus erythematosus (LE). A common mechanism underlying the immunopathologic effect, resulting from exposure to these two seemingly unrelated factors, remains unknown. The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of IL-22 production in humans and can be activated by both xenobiotics and naturally occurring photoproducts. A significant expansion of Th17 and Th22 cells was observed in the peripheral blood of active systemic LE (SLE) patients, compared to inactive patients and controls. We also show that propranolol, a potential lupus-inducing drug, induced stronger AhR activation in PBMCs of SLE patients than in those of controls. AhR agonist activity of propranolol was enhanced by UV light exposure. MS analysis of irradiated propranolol revealed the generation of a proinflammatory photoproduct. This compound behaves like the prototypic AhR ligand 6-formylindolo[3,2-b]carbazole, a cutaneous UV light-induced tryptophan metabolite, both promoting IL-22, IL-8, and CCL2 secretion by T-cells and macrophages. Finally, LE patients exhibit signs of cutaneous AhR activation that correlate with lesional expression of the same proinflammatory cytokines, suggesting a role for photometabolites in the induction of skin inflammation. The AhR might therefore represent a target for therapeutic intervention in LE.

  12. Effects of enzyme induction on the distribution of the food carcinogen 2-amino-3,8-dimethyl-imidazo[4,5-ss]-quinoxaline (MeIQx) in Ah-receptor- responsive- and Ah-receptor-non-responsive mice.

    PubMed

    Vikse, R; Ingebrigtsen, K; Klungsøyr, L; Alexander, J

    1995-07-01

    The distribution of the food carcinogen 2-amino-3,8-dimethyl-imidazo[4,5-ss]quinoxaline (MeIQx) was studied in Ah-responsive-(C57BL/6J) and Ah-non-responsive mice (DBA/2N). The time dependent organ distribution of radioactivity after 14C-MeIQx (10 mg/kg) administration in C57BL/6J showed that at day 4 most of the radioactivity had been excreted and that the remaining radioactivity was found in liver, kidneys, lungs and spleen. C57BL/6J bound more radioactivity in the kidneys than the DBA/2N strain whereas approximately the same amount was left in the liver and lungs in both strains 4 days after MeIQx exposure. Liver microsomes of the two strains had approximately the same ability to activate MeIQx in the Ames Salmonella assay. beta-Naphthoflavone treatment of the animals greatly increased microsomal activating capacity, but only in the C57BL/6J strain. Isosafrole treatment of the animals only slightly increased the activating capacity, but particularly with microsomes from the DBA/2N strain, displacement of the putative inhibitory isosafrole metabolite greatly increased their activating capacity. In the whole animals pretreatment with beta-naphthoflavone, which induces P450IA only in the C57BL/6J strain, did not significantly change the amount of retained radioactivity in any of the strains. Isosafrole induces only P450IA2, the major N2-hydroxylating enzyme of heterocyclic amines, in both strains. Such pretreatment reduced the amount retained in the kidney of both strains whereas it reduced the retained amount of radioactivity in the liver with about 60% only in the Ah-non-responsive strain (DBA/2N). The effect of isosafrole did not persist when MeIQx was given three days after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. 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

  14. Ir A.H. de Voogt: life and career of a radio pioneer

    NASA Astrophysics Data System (ADS)

    Strom, R. G.

    2007-06-01

    There are probably few radio astronomers who would be able to recall A.H. de Voogt, which is unfortunate, but at the same time unsurprising: for he published no original astronomical research, never carried out pioneering observations, nor is his name linked to either theoretical or instrumental breakthroughs. Yet he was described by the man who first observed the 21 cm hydrogen line from the Netherlands as a radio astronomy pioneer, at the very birth of the Dutch effort. He was, moreover, a trail blazer at the cutting edge of radio, not once but twice in his career. Without him it is unlikely that the 21 cm line would have been observed in the Netherlands in 1951, and arguably the H I mapping of the Milky Way under Jan Oort's leadership would have taken place much later, if at all. Radio astronomy observing itself might well have been compromised by interference had it not been for De Voogt's foresight. \\ Anthonet Hugo de Voogt (1892-1969) built, while still a teenager, one of the very first amateur radio stations (call letters VO: *** -/- - -) in Holland, earned the radio-telegrapher's diploma during his student days, and was intimately involved in the foundation of the Dutch Society for Radio-Telegraphy in 1916. Until the 1920s, he was very active in amateur radio and astronomy circles. Trained in electrical engineering at Delft, he joined the PTT (Post Office) as a telegraph engineer in 1919, worked his way through the ranks to become head of the telephone district of Breda in 1939, and was promoted to head the PTT Radio Service just days after the end of the war. As his department was responsible for overseas radio communication, he initiated a research effort to study radio propagation in the ionosphere and the effects of solar activity. To this end, he rescued a number of Würzburg-Riese 7.5-m radar antennas abandoned at the end of the war, made one available for Jan Oort's H I work, and launched a series of radio astronomical initiatives. His group also

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

    PubMed Central

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

    2012-01-01

    Background 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. Methods 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. Results 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

  16. 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

  17. Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

    PubMed Central

    Desdouits, Marion; Munier, Sandie; Prevost, Marie-Christine; Jeannin, Patricia; Butler-Browne, Gillian; Ozden, Simona; Gessain, Antoine; Van Der Werf, Sylvie; Naffakh, Nadia; Ceccaldi, Pierre-Emmanuel

    2013-01-01

    Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients. PMID:24223983

  18. Penetrability of AH plus and MTA fillapex after endodontic treatment and retreatment: a confocal laser scanning microscopy study.

    PubMed

    Kok, Daniela; Rosa, Ricardo Abreu da; Barreto, Mirela Sangoi; Busanello, Fernanda Hoffmann; Santini, Manuela Favarin; Pereira, Jefferson Ricardo; Só, Marcus Vinícius Reis

    2014-06-01

    The aim of the study was to assess the penetrability of two endodontic sealers (AH Plus and MTA Fillapex) into dentinal tubules, submitted to endodontic treatment and subsequently to endodontic retreatment. Thirty ex vivo incisors were prepared using ProTaper rotary system up to F3 instrument and divided in three groups according to the endodontic sealer used for root canal filling: AH Plus (AHP), MTA Fillapex (MTAF), and control group (CG) without using EDTA previously to the root canal filling. Rhodamine B dye (red) was incorporated to the sealers in order to provide the fluorescence which will enable confocal laser scanning microscopy (CLSM) assessment. All specimens were filled with gutta-percha cones using the lateral compaction technique. The specimens were submitted to endodontic retreatment using ProTaper Retreatment system, re-prepared up to F5 instruments and filled with gutta-percha cones and the same sealer used during endodontic retreatment. Fluorescein dye (green) was incorporated to the sealer in order to distinguish from the first filling. The roots were sectioned 2 mm from the apex and assessed by CLSM. No difference was found between the two experimental groups (P > 0.05). On the other hand, in the control group the sealers were not capable to penetrate into dentinal tubules after endodontic treatment (P > 0.05). In retreatment cases, none of the sealers were able to penetrate into dentin tubules. It can be concluded that sealer penetrability is high during endodontic treatment. However, MTA Fillapex and AH Plus do not penetrate into dentinal tubules after endodontic retreatment.

  19. 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.

  20. Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013.

    PubMed

    Sleeman, K; Mishin, V P; Guo, Z; Garten, R J; Balish, A; Fry, A M; Villanueva, J; Stevens, J; Gubareva, L V

    2014-01-01

    Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n=168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs.

  1. AhDMT1, a Fe(2+) transporter, is involved in improving iron nutrition and N2 fixation in nodules of peanut intercropped with maize in calcareous soils.

    PubMed

    Shen, Hongyun; Xiong, Hongchun; Guo, Xiaotong; Wang, Pengfei; Duan, Penggen; Zhang, Lixia; Zhang, Fusuo; Zuo, Yuanmei

    2014-05-01

    Peanut (Arachis hypogaea L.) is an important legume providing edible proteins and N2 fixation. However, iron deficiency severely reduces peanut growth in calcareous soils. The maize/peanut intercropping effectively improves iron nutrition and N2 fixation of peanut under pot and field conditions on calcareous soils. However, little was known of how intercropping regulates iron transporters in peanut. We identified AhDMT1 as a Fe(2+) transporter which was highly expressed in mature nodules with stronger N2 fixation capacity. Promoter expression analysis indicated that AhDMT1 was localized in the vascular tissues of both roots and nodules in peanut. Short-term Fe-deficiency temporarily induced an AhDmt1 expression in mature nodules in contrast to roots. However, analysis of the correlation between the complex regulation pattern of AhDmt1 expression and iron nutrition status indicated that sufficient iron supply for long term was a prerequisite for keeping AhDmt1 at a high expression level in both, peanut roots and mature nodules. The AhDmt1 expression in peanut intercropped with maize under 3 years greenhouse experiments was similar to that of peanut supplied with sufficient iron in laboratory experiments. Thus, the positive interspecific effect of intercropping may supply sufficient iron to enhance the expression of AhDmt1 in peanut roots and mature nodules to improve the iron nutrition and N2 fixation in nodules. This study may also serve as a paradigm in which functionally important genes and their ecological significance in intercropping were characterized using a candidate gene approach.

  2. 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. PMID:24548649

  3. Simultaneous discrimination and detection of influenza A(H1N1)pdm09 and seasonal influenza A viruses using a rapid immunogold biosensor.

    PubMed

    Apiwat, Chayachon; Wiriyachaiporn, Natpapas; Maneeprakorn, Weerakanya; Dharakul, Tararaj; Thepthai, Charin; Puthavathana, Pilaipan; Siritantikorn, Sontana; Horthongkham, Navin

    2014-07-01

    A rapid immunogold biosensor for the simultaneous discrimination of influenza A(H1N1)pdm09 and seasonal influenza A viruses was developed successfully. Monoclonal antibodies (mAbs) that were specific for the hemagglutinin protein of the A(H1N1)pdm09 virus were produced, and the best mAb pairs were selected. Using an mAb that was specific for the influenza A nucleoprotein, a rapid immunogold biosensor for the discrimination and detection of A(H1N1)pdm09/seasonal influenza viruses was developed. When tested with 72 virus isolates, the system achieved 100 % detection of the A(H1N1)pdm09 virus without cross-reactivity against seasonal influenza A (H1, H3 subtypes) and B viruses, parainfluenza viruses, respiratory syncytial viruses, and adenoviruses. The detection limits for A(H1N1)pdm09 and seasonal strains were 5 × 10(2)-7.5 × 10(3) and 1 × 10(3)-7.5 × 10(5) TCID50/mL, respectively. When tested with 49 clinical specimens, the specificity was high (100 %). The sensitivity for the detection of A(H1N1)pdm09 and seasonal strains was 90 % and 100 %, respectively, which correlated with the results of real-time reverse transcription polymerase chain reaction as a reference method. The ability of the system to detect and discriminate the A(H1N1)pdm09 strain from the seasonal strains suggests that this method may be beneficial for investigation of outbreaks and diagnostic applications. Furthermore, this method might be a useful platform for developing a rapid diagnostic system for the simultaneous discrimination of other influenza virus subtypes during future outbreaks. PMID:24402634

  4. 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

  5. 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.

  6. 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. PMID:27180721

  7. Effect of LEO cycling on 125 Ah advanced design IPV nickel-hydrogen flight cells. An update

    NASA Technical Reports Server (NTRS)

    Smithrick, John J.; Hall, Stephen W.

    1991-01-01

    Validation testing of the NASA Lewis 125 Ah advanced design individual pressure vessel (IPV) nickel-hydrogen flight cells was conducted. Work consisted of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, an open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells were cycled for over 11,000 cycles with no cell failures in the continuing test. One of the noncatalyzed wall wick cells failed.

  8. Multiyear Persistence of 2 Pandemic A/H1N1 Influenza Virus Lineages in West Africa

    PubMed Central

    Nelson, Martha I.; Njouom, Richard; Viboud, Cecile; Niang, Mbayame N. D.; Kadjo, Hervé; Ampofo, William; Adebayo, Adedeji; Tarnagda, Zekiba; Miller, Mark A.; Holmes, Edward C.; Diop, Ousmane M.

    2014-01-01

    Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009–2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas. PMID:24446525

  9. In vitro inactivation of two Egyptian A/H5N1 viruses by four commercial chemical disinfectants.

    PubMed

    Marzouk, Eman; Abd El-Hamid, Hatem S; Awad, Ashraf M; Zessin, Karl-Hans; Abdelwhab, E M; Hafez, Hafez M

    2014-09-01

    The highly pathogenic H5N1 avian influenza virus (A/H5N1) devastated the poultry industry and posed a serious health threat. Cleaning and disinfection are essential parts of preventative and postoutbreak management of A/H5N1 infections in poultry. In this preliminary study, we used suspension and carrier tests to evaluate the impact of concentration, time of exposure, surface porosity, and organic matter on the ability of four commercial chemical disinfectants to inactivate two A/H5N1 viruses of clade 2.2.1 isolated in 2006 and 2010 from broiler flocks in Egypt. Viruses were incubated with 0.5%, 1%, and 2% of formalin, glutaraldehyde, TH4, and Virkon S for 15, 30, 60, and 120 min at room temperature (22 +/- 2 C). In suspension tests, in the absence of organic matter, all disinfectants, at each concentration, except Virkon S 0.5%, effectively inactivated virus suspensions after a 15-min exposure time. In the presence of organic matter, the use of low concentrations of formalin (0.5%), glutaraldehyde (0.5%), or Virkon S (0.5%) was not sufficient to inactivate the viruses after 15 min. In gauze carrier tests, only formalin at any concentration for 15 min was sufficient to inactivate the viruses, whereas different concentrations or exposure times were required for glutaraldehyde (0.5% for 60 min), TH4 (0.5% for 30 min), and Virkon S (0.5% for 60 min or 1% for 30 min). In wood carrier tests, total inactivation of the virus was obtained at concentrations of 0.5% for 30 min (formalin and TH4) or 60 min (glutaraldehyde and Virkon S). This study emphasizes the need to use high concentrations of and/or extended time of exposure to disinfectants for efficient inactivation of A/H5N1, particularly in the presence of organic matter or different surfaces, which are common in poultry operations. In addition, it seemed that the virus isolated in 2010 was more resistant to disinfectants than the isolate from 2006 when wood was used as a carrier.

  10. 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

  11. The value of radiographic findings for the progression of pandemic 2009 influenza A/H1N1 virus infection

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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). Conclusions Consolidation on initial chest radiographs was the most significant factor to predict clinical course of hospitalized children with the 2009 A/H1N1 infection. PMID

  12. 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

  13. 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

  14. Molecular breeding for introgression of fatty acid desaturase mutant alleles (ahFAD2A and ahFAD2B) enhances oil quality in high and low oil containing peanut genotypes.

    PubMed

    Janila, Pasupuleti; Pandey, Manish K; Shasidhar, Yaduru; Variath, Murali T; Sriswathi, Manda; Khera, Pawan; Manohar, Surendra S; Nagesh, Patne; Vishwakarma, Manish K; Mishra, Gyan P; Radhakrishnan, T; Manivannan, N; Dobariya, K L; Vasanthi, R P; Varshney, Rajeev K

    2016-01-01

    High oleate peanuts have two marketable benefits, health benefits to consumers and extended shelf life of peanut products. Two mutant alleles present on linkage group a09 (ahFAD2A) and b09 (ahFAD2B) control composition of three major fatty acids, oleic, linoleic and palmitic acids which together determine peanut oil quality. In conventional breeding, selection for fatty acid composition is delayed to advanced generations. However by using DNA markers, breeders can reject large number of plants in early generations and therefore can optimize time and resources. Here, two approaches of molecular breeding namely marker-assisted backcrossing (MABC) and marker-assisted selection (MAS) were employed to transfer two FAD2 mutant alleles from SunOleic 95R into the genetic background of ICGV 06110, ICGV 06142 and ICGV 06420. In summary, 82 MABC and 387 MAS derived introgression lines (ILs) were developed using DNA markers with elevated oleic acid varying from 62 to 83%. Oleic acid increased by 0.5-1.1 folds, with concomitant reduction of linoleic acid by 0.4-1.0 folds and palmitic acid by 0.1-0.6 folds among ILs compared to recurrent parents. Finally, high oleate ILs, 27 with high oil (53-58%), and 28 ILs with low oil content (42-50%) were selected that may be released for cultivation upon further evaluation. PMID:26566838

  15. Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [99mTc] (AH-113018) or Cy 5** (AH-112543) Labeled Peptide.

    PubMed

    Jagoda, Elaine M; Bhattacharyya, Sibaprasad; Kalen, Joseph; Riffle, Lisa; Leeder, Avrum; Histed, Stephanie; Williams, Mark; Wong, Karen J; Xu, Biying; Szajek, Lawrence P; Elbuluk, Osama; Cecchi, Fabiola; Raffensperger, Kristen; Golla, Meghana; Bottaro, Donald P; Choyke, Peter

    2015-01-01

    Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIs). A peptide targeting Met labeled with [(99m)Tc] had high affinity in vitro (Kd = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [(99m)Tc]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using single-photon emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [(99m)Tc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [(99m)Tc]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [(99m)Tc] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [(99m)Tc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications. PMID:26461980

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

    PubMed Central

    2010-01-01

    A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population. PMID:20738882

  17. Limited human-to-human transmission of avian influenza A(H7N9) virus, Shanghai, China, March to April 2013.

    PubMed

    Hu, J; Zhu, Y; Zhao, B; Li, J; Liu, L; Gu, K; Zhang, W; Su, H; Teng, Z; Tang, S; Yuan, Z; Feng, Z; Wu, F

    2014-01-01

    In April 2013, two members of one family were successively confirmed as cases of avian influenza A(H7N9) virus infection in Shanghai, China. Respiratory specimens from the two cases and their close contacts were tested using real-time reverse-transcription (RT)-PCR. Paired serum specimens from contacts were tested by haemagglutination inhibition assay and microneutralisation test. The index patient developed severe pneumonia. Her husband presented with pneumonia shortly thereafter. Both cases had highly similar clinical features and infection with A(H7N9) virus was confirmed in both cases by genetic analysis. Phylogenetic analysis revealed a high level of similarity between the sequences from the two patients and environmental samples collected from wet markets in Minhang and Changning districts. Six samples from the Changning wet market were confirmed as A(H7N9) positive. Of 27 close contacts, one developed mild respiratory symptoms and another tested positive for A(H7N9) antibodies, but both were negative by real-time RT-PCR. The other 25 close contacts of both cases were A(H7N9) negative. Limited human-to-human transmission of the virus most likely occurred in the family cluster. However, other close contacts did not test positive for the virus, suggesting limited potential for extensive human-to-human transmission of the virus.

  18. Effect-directed analysis and mixture effects of AhR-active PAHs in crude oil and coastal sediments contaminated by the Hebei Spirit oil spill.

    PubMed

    Hong, Seongjin; Lee, Sangwoo; Choi, Kyungho; Kim, Gi Beum; Ha, Sung Yong; Kwon, Bong-Oh; Ryu, Jongseong; Yim, Un Hyuk; Shim, Won Joon; Jung, Jinho; Giesy, John P; Khim, Jong Seong

    2015-04-01

    The major AhR-active PAHs were identified in crude oil and oil-contaminated sediments by use of effect-directed analysis. As part of the study, an enhanced potency balance analysis was conducted by establishing the novel relative potency values of (alkyl)-PAHs from the H4IIE-luc bioassay. Silica gel column fractionation of crude oil resulted in greater AhR-mediated potencies in fractions of aromatics (F2) and resins (F3), and such trend was also observed for field collected sediment samples. AhR-mediated potencies of six F2 sub-fractions from HPLC indicated that the majority of F2 responses were attributable to 3-4 ring aromatics. Target PAHs including C4-phenanthrene, C1-chrysene, and C3-chrysene in sediments explained ∼ 18% of the bioassay-derived TCDD-EQs, however, the unknown AhR agonists and potential mixture effects remain in question. Overall, the AhR-potency and antagonistic potential of residual oil in sediment tended to decrease over time, thus monitoring of weathering process would be key for the post management of oil-contaminated sites. PMID:25645060

  19. Aromatic hydrocarbons upregulate glyceraldehyde-3-phosphate dehydrogenase and induce changes in actin cytoskeleton. Role of the aryl hydrocarbon receptor (AhR).

    PubMed

    Reyes-Hernández, O D; Mejía-García, A; Sánchez-Ocampo, E M; Castro-Muñozledo, F; Hernández-Muñoz, R; Elizondo, G

    2009-12-21

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme involved in several cellular functions including glycolysis, membrane transport, microtubule assembly, DNA replication and repair, nuclear RNA export, apoptosis, and the detection of nitric oxide stress. Therefore, modifications in the regulatory ability and function of GAPDH may alter cellular homeostasis. We report here that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-naphthoflavone, which are well-known ligands for the aryl hydrocarbon receptor (AhR), increase GAPDH mRNA levels in vivo and in vitro, respectively. These compounds fail to induce GAPDH transcription in an AhR-null mouse model, suggesting that the increase in GAPDH level is dependent upon AhR activation. To analyse the consequences of AhR ligands on GAPDH function, mice were treated with TCDD and the level of liver activity of GAPDH was determined. The results showed that TCDD treatment increased GAPDH activity. On the other hand, treatment of Hepa-1 cells with beta-naphthoflavone leads to an increase in microfilament density when compared to untreated cultures. Collectively, these results suggest that AhR ligands, such as polycyclic hydrocarbons, can modify GAPDH expression and, therefore, have the potential to alter the multiple functions of this enzyme.

  20. KCa1.1 is potential marker for distinguishing Ah-type baroreceptor neurons in NTS and contributes to sex-specific presynaptic neurotransmission in baroreflex afferent pathway.

    PubMed

    Zhang, Yu-Yao; Yan, Zhen-Yu; Qu, Mei-Yu; Guo, Xin-Jing; Li, Guo; Lu, Xiao-Long; Liu, Yang; Ban, Tao; Sun, Hong-Li; Qiao, Guo-Fen; Li, Bai-Yan

    2015-09-14

    Sexual-dimorphic neurocontrol of circulation has been described in baroreflex due largely to the function of myelinated Ah-type baroreceptor neurons (BRNs, 1st-order) in nodose. However, it remains unclear if sex- and afferent-specific neurotransmission could also be observed in the central synapses within nucleus of solitary track (NTS, 2nd-order). According to the principle of no mixed neurotransmission among afferents and differentiation of Ah- and A-types to iberiotoxin (IbTX) observed in nodose, the 2nd-order Ah-type BRNs are highly expected. To test this hypothesis, the excitatory post-synaptic currents (EPSCs) were recorded in identified 2nd-order BRNs before and after IbTX using brain slice and whole-cell patch. These results showed that, in male rats, the dynamics of EPSCs in capsaicin-sensitive C-types were dramatically altered by IbTX, but not in capsaicin-insensitive A-types. Interestingly, near 50% capsaicin-insensitive neurons in females showed similar effects to C-types, suggesting the existence of Ah-types in NTS, which may be the likely reason why the females had lower blood pressure and higher sensitivity to aortic depressor nerve stimulation via KCa1.1-mediated presynaptic glutamate release from Ah-type afferent terminals.

  1. Effect-directed analysis and mixture effects of AhR-active PAHs in crude oil and coastal sediments contaminated by the Hebei Spirit oil spill.

    PubMed

    Hong, Seongjin; Lee, Sangwoo; Choi, Kyungho; Kim, Gi Beum; Ha, Sung Yong; Kwon, Bong-Oh; Ryu, Jongseong; Yim, Un Hyuk; Shim, Won Joon; Jung, Jinho; Giesy, John P; Khim, Jong Seong

    2015-04-01

    The major AhR-active PAHs were identified in crude oil and oil-contaminated sediments by use of effect-directed analysis. As part of the study, an enhanced potency balance analysis was conducted by establishing the novel relative potency values of (alkyl)-PAHs from the H4IIE-luc bioassay. Silica gel column fractionation of crude oil resulted in greater AhR-mediated potencies in fractions of aromatics (F2) and resins (F3), and such trend was also observed for field collected sediment samples. AhR-mediated potencies of six F2 sub-fractions from HPLC indicated that the majority of F2 responses were attributable to 3-4 ring aromatics. Target PAHs including C4-phenanthrene, C1-chrysene, and C3-chrysene in sediments explained ∼ 18% of the bioassay-derived TCDD-EQs, however, the unknown AhR agonists and potential mixture effects remain in question. Overall, the AhR-potency and antagonistic potential of residual oil in sediment tended to decrease over time, thus monitoring of weathering process would be key for the post management of oil-contaminated sites.

  2. Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

    PubMed

    Tanaka, Seiji; Saikusa, Tomoko; Katafuchi, Yuno; Ushijima, Kosuke; Ohtsu, Yasushi; Tsumura, Naoki; Ito, Yuhei

    2015-09-11

    A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.

  3. RNA interference targeting CYP76AH1 in hairy roots of Salvia miltiorrhiza reveals its key role in the biosynthetic pathway of tanshinones.

    PubMed

    Ma, Ying; Ma, Xiao-Hui; Meng, Fan-Yun; Zhan, Zhi-Lai; Guo, Juan; Huang, Lu-Qi

    2016-08-19

    Plant cytochrome P450s (CYPs) are well known as the largest family of enzymes that contribute to both primary metabolism and the chemical diversity of plant secondary metabolites. It is important to elucidate the in vivo role of CYPs in secondary metabolism, in order to apply them in the production of valuable metabolites in medicinal plants via metabolic engineering. CYP76AH1 has been suggested to catalyze the conversion of the carbon skeleton miltiradiene into the intermediate ferruginol, which is involved in the biosynthesis of tanshinones, the chief bioactive ingredients of Salvia miltiorrhiza. However, its role in planta remains to be elucidated. In this work, we constructed a CYP76AH1 RNAi system for hairy roots. Metabolic analysis of RNAi-AH1 hairy root lines showed a significantly increased accumulation of miltiradiene compared to the control lines. At the same time, the concentration of ferruginol decreased revealing the in vivo catalytic activity of CYP76AH1. The content of tanshinones decreased significantly after silencing of CYP76AH1, which verified its key role in the biosynthesis of tanshinones, and indicated that it could be used as a target for metabolic engineering. PMID:27291148

  4. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1) Virus Impairs the Human T Cell Response

    PubMed Central

    Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus. PMID:24187568

  5. PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response.

    PubMed

    Valero-Pacheco, Nuriban; Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8⁺ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8⁺ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus.

  6. Polar Glycosylated and Lateral Non-Glycosylated Flagella from Aeromonas hydrophila Strain AH-1 (Serotype O11)

    PubMed Central

    Fulton, Kelly M.; Mendoza-Barberá, Elena; Twine, Susan M.; Tomás, Juan M.; Merino, Susana

    2015-01-01

    Polar and but not lateral flagellin proteins from Aeromonas hydrophila strain AH-1 (serotype O11) were found to be glycosylated. Top-down mass spectrometry studies of purified polar flagellins suggested the presence of a 403 Da glycan of mass. Bottom-up mass spectrometry studies showed the polar flagellin peptides to be modified with 403 Da glycans in O-linkage. The MS fragmentation pattern of this putative glycan was similar to that of pseudaminic acid derivative. Mutants lacking the biosynthesis of pseudaminic acid (pseB and pseI homologues) were unable to produce polar flagella but no changes were observed in lateral flagella by post-transcriptional regulation of the flagellin. Complementation was achieved by reintroduction of the wild-type pseB and pseI. We compared two pathogenic features (adhesion to eukaryotic cells and biofilm production) between the wild-type strain and two kinds of mutants: mutants lacking polar flagella glycosylation and lacking the O11-antigen lipopolysaccharide (LPS) but with unaltered polar flagella glycosylation. Results suggest that polar flagella glycosylation is extremely important for A. hydrophila AH-1 adhesion to Hep-2 cells and biofilm formation. In addition, we show the importance of the polar flagella glycosylation for immune stimulation of IL-8 production via toll-“like” receptor 5 (TLR5). PMID:26633358

  7. The bond strength of adhesive resins to AH plus contaminated dentin cleaned by various gutta-percha solvents.

    PubMed

    Topçuoğlu, Hüseyin Sinan; Demirbuga, Sezer; Pala, Kansad; Cayabatmaz, Muhammed; Topçuoğlu, Gamze

    2015-01-01

    The optimal bonding of adhesives to dentin requires the sealer to be completely removed from dentinal walls. The aim of this study was to investigate the effect of different cleaning procedures using gutta-percha solvents on bond strength of adhesive resins to AH Plus contaminated dentin (APCD). The pulp chamber dentin surfaces were contaminated with AH Plus and cleaned with five different techniques (dry cotton, chloroform, orange oil, eucalyptol, and ethanol). Then, Clearfil SE Bond (CSE) (Kuraray), and Tetric N Bond (TNB) (Ivoclar Vivadent) were applied and filled with a composite resin. The serial sticks (1 × 1 mm) were obtained and tested for microtensile bond strength. Scanning electron microscopy (SEM) was used for analysis of debonded surfaces. Ethanol exhibited the highest bond strength to APCD followed by dry cotton. There was no statistically significant difference between ethanol and dry cotton (p > 0.05). Eucalyptol showed the lowest bond strength to APCD and statistically significant differences (p < 0.05) in comparison with other groups. APCD reduced the bond strength of all adhesive resins. Dry cotton, ethanol, and chloroform were the most suitable techniques when used with CSE together, whereas ethanol was best with TNB.

  8. Polar Glycosylated and Lateral Non-Glycosylated Flagella from Aeromonas hydrophila Strain AH-1 (Serotype O11).

    PubMed

    Fulton, Kelly M; Mendoza-Barberá, Elena; Twine, Susan M; Tomás, Juan M; Merino, Susana

    2015-01-01

    Polar and but not lateral flagellin proteins from Aeromonas hydrophila strain AH-1 (serotype O11) were found to be glycosylated. Top-down mass spectrometry studies of purified polar flagellins suggested the presence of a 403 Da glycan of mass. Bottom-up mass spectrometry studies showed the polar flagellin peptides to be modified with 403 Da glycans in O-linkage. The MS fragmentation pattern of this putative glycan was similar to that of pseudaminic acid derivative. Mutants lacking the biosynthesis of pseudaminic acid (pseB and pseI homologues) were unable to produce polar flagella but no changes were observed in lateral flagella by post-transcriptional regulation of the flagellin. Complementation was achieved by reintroduction of the wild-type pseB and pseI. We compared two pathogenic features (adhesion to eukaryotic cells and biofilm production) between the wild-type strain and two kinds of mutants: mutants lacking polar flagella glycosylation and lacking the O11-antigen lipopolysaccharide (LPS) but with unaltered polar flagella glycosylation. Results suggest that polar flagella glycosylation is extremely important for A. hydrophila AH-1 adhesion to Hep-2 cells and biofilm formation. In addition, we show the importance of the polar flagella glycosylation for immune stimulation of IL-8 production via toll-"like" receptor 5 (TLR5). PMID:26633358

  9. Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers.

    PubMed

    Shaytan, Alexey K; Landsman, David; Panchenko, Anna R

    2015-06-01

    Nucleosome variability is essential for their functions in compacting the chromatin structure and regulation of transcription, replication and cell reprogramming. The DNA molecule in nucleosomes is wrapped around an octamer composed of four types of core histones (H3, H4, H2A, H2B). Nucleosomes represent dynamic entities and may change their conformation, stability and binding properties by employing different sets of histone variants or by becoming post-translationally modified. There are many variants of histones H2A and H2B. Specific H2A and H2B variants may preferentially associate with each other resulting in different combinations of variants and leading to the increased combinatorial complexity of nucleosomes. In addition, the H2A-H2B dimer can be recognized and substituted by chaperones/remodelers as a distinct unit, can assemble independently and is stable during nucleosome unwinding. In this review we discuss how sequence and structural variations in H2A-H2B dimers may provide necessary complexity and confer the nucleosome functional variability.

  10. Antigenic Maps of Influenza A(H3N2) Produced With Human Antisera Obtained After Primary Infection

    PubMed Central

    Fonville, Judith M.; Fraaij, Pieter L. A.; de Mutsert, Gerrie; Wilks, Samuel H.; van Beek, Ruud; Fouchier, Ron A. M.; Rimmelzwaan, Guus F.

    2016-01-01

    Background Antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (HI) assay data for viral isolates tested against strain-specific postinfection ferret antisera. Here, similar virus characterizations were performed using serological data from humans with primary influenza A(H3N2) infection. Methods We screened sera collected between 1995 and 2011 from children between 9 and 24 months of age for influenza virus antibodies, performed HI tests for the positive sera against 23 influenza viruses isolated between 1989 and 2011, and measured HI titers of antisera against influenza A(H3N2) from 24 ferrets against the same panel of viruses. Results Of the 17 positive human sera, 6 had a high response, showing HI patterns that would be expected from primary infection antisera, while 11 sera had lower, more dispersed patterns of reactivity that are not easily explained. The antigenic map based on the high-response human HI data was similar to the map created using ferret data. Conclusions Although the overall structure of the ferret and human antigenic maps is similar, local differences in virus positions indicate that the human and ferret immune system might see antigenic properties of viruses differently. Further studies are needed to establish the degree of similarity between serological patterns in ferret and human data. PMID:26142433

  11. Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers

    PubMed Central

    Shaytan, Alexey K.; Landsman, David

    2015-01-01

    Nucleosome variability is essential for their functions in compacting the chromatin structure and regulation of transcription, replication and cell reprogramming. The DNA molecule in nucleosomes is wrapped around an octamer composed of four types of core histones (H3, H4, H2A, H2B). Nucleosomes represent dynamic entities and may change their conformation, stability and binding properties by employing different sets of histone variants or by becoming post-translationally modified. There are many variants of histones H2A and H2B. Specific H2A and H2B variants may preferentially associate with each other resulting in different combinations of variants and leading to the increased combinatorial complexity of nucleosomes. In addition, the H2A-H2B dimer can be recognized and substituted by chaperones/remodelers as a distinct unit, can assemble independently and is stable during nucleosome unwinding. In this review we discuss how sequence and structural variations in H2A-H2B dimers may provide necessary complexity and confer the nucleosome functional variability. PMID:25731851

  12. Human Infection with Influenza A(H7N9) Virus during 3 Major Epidemic Waves, China, 2013–2015

    PubMed Central

    Wu, Peng; Peng, Zhibin; Fang, Vicky J.; Feng, Luzhao; Tsang, Tim K.; Jiang, Hui; Lau, Eric H.Y.; Yang, Juan; Zheng, Jiandong; Qin, Ying; Li, Zhongjie; Leung, Gabriel M.; Cowling, Benjamin J.

    2016-01-01

    Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory-confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions. Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity. PMID:27191934

  13. Calculation of flight vibration levels of the AH-1G helicopter and correlation with existing flight vibration measurements

    NASA Technical Reports Server (NTRS)

    Sopher, R.; Twomey, W. J.

    1990-01-01

    NASA-Langley is sponsoring a rotorcraft structural dynamics program with the objective to establish in the U.S. a superior capability to utilize finite element analysis models for calculations to support industrial design of helicopter airframe structures. In the initial phase of the program, teams from the major U.S. manufacturers of helicopter airframes will apply extant finite element analysis methods to calculate loads and vibrations of helicopter airframes, and perform correlations between analysis and measurements. The aforementioned rotorcraft structural dynamics program was given the acronym DAMVIBS (Design Analysis Method for Vibrations). Sikorsky's RDYNE Rotorcraft Dynamics Analysis used for the correlation study, the specifics of the application of RDYNE to the AH-1G, and comparisons of the predictions of the method with flight data for loads and vibrations on the AH-1G are described. RDYNE was able to predict trends of variations of loads and vibrations with airspeed, but in some instances magnitudes differed from measured results by factors of two or three to one. Sensitivities were studied of predictions to rotor inflow modeling, effects of torsional modes, number of blade bending modes, fuselage structural damping, and hub modal content.

  14. Polar Glycosylated and Lateral Non-Glycosylated Flagella from Aeromonas hydrophila Strain AH-1 (Serotype O11).

    PubMed

    Fulton, Kelly M; Mendoza-Barberá, Elena; Twine, Susan M; Tomás, Juan M; Merino, Susana

    2015-01-01

    Polar and but not lateral flagellin proteins from Aeromonas hydrophila strain AH-1 (serotype O11) were found to be glycosylated. Top-down mass spectrometry studies of purified polar flagellins suggested the presence of a 403 Da glycan of mass. Bottom-up mass spectrometry studies showed the polar flagellin peptides to be modified with 403 Da glycans in O-linkage. The MS fragmentation pattern of this putative glycan was similar to that of pseudaminic acid derivative. Mutants lacking the biosynthesis of pseudaminic acid (pseB and pseI homologues) were unable to produce polar flagella but no changes were observed in lateral flagella by post-transcriptional regulation of the flagellin. Complementation was achieved by reintroduction of the wild-type pseB and pseI. We compared two pathogenic features (adhesion to eukaryotic cells and biofilm production) between the wild-type strain and two kinds of mutants: mutants lacking polar flagella glycosylation and lacking the O11-antigen lipopolysaccharide (LPS) but with unaltered polar flagella glycosylation. Results suggest that polar flagella glycosylation is extremely important for A. hydrophila AH-1 adhesion to Hep-2 cells and biofilm formation. In addition, we show the importance of the polar flagella glycosylation for immune stimulation of IL-8 production via toll-"like" receptor 5 (TLR5).

  15. A case of central diabetes insipidus following probable type A/H1N1 influenza infection.

    PubMed

    Kobayashi, Takaaki; Miwa, Takashi; Odawara, Masato

    2011-01-01

    The major causes of central diabetes insipidus (CDI) are neoplastic or infiltrative lesions of the hypothalamus or pituitary gland, severe head injuries, or pituitary or hypothalamic surgery. Lymphocytic infundibuloneurophysitis (LINH) is associated with autoimmune inflammatory disease of the pituitary gland, but the exact etiology is unknown. CDI caused by viral infections has been rarely reported. Here, we describe the case of a 22-year-old man who was in good health until 2 months prior to admission, presented with acute development of polyuria and polydipsia, and showed increased urinary volume up to 9000 mL/day. The patient showed elevated serum osmolality and low urine osmolality, with a low level of antidiuretic hormone. Endocrinological findings revealed CDI, but his arterial pituitary function appeared normal. Magnetic resonance imaging revealed significant enlargement of the pituitary stalk. We suspected CDI due to LINH based on non-transsphenoidal biopsy findings. He was diagnosed as type A influenza,and given oral therapeutic agents. However, acute onset of polyuria and polydipsia occurred 10 days after the influenza diagnosis. The available epidemiological information regarding the outbreak of influenza around that time strongly suggested that the patient was infected with the A/H1N1 influenza virus, although this virus had not been detected on polymerase chain reaction testing. In the present case, the autoimmune mechanism of LINH may have been associated with novel influenza A/H1N1 virus infection.

  16. Human Infection with Influenza A(H7N9) Virus during 3 Major Epidemic Waves, China, 2013-2015.

    PubMed

    Wu, Peng; Peng, Zhibin; Fang, Vicky J; Feng, Luzhao; Tsang, Tim K; Jiang, Hui; Lau, Eric H Y; Yang, Juan; Zheng, Jiandong; Qin, Ying; Li, Zhongjie; Leung, Gabriel M; Yu, Hongjie; Cowling, Benjamin J

    2016-06-01

    Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory-confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions. Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity. PMID:27191934

  17. Surveillance of human influenza A(H3N2) virus from 1999 to 2009 in southern Italy.

    PubMed

    DE Donno, A; Idolo, A; Quattrocchi, M; Zizza, A; Gabutti, G; Romano, A; Grima, P; Donatelli, I; Guido, M

    2014-05-01

    The aim of this study was to evaluate the presence of influenza virus co-infections in humans and changes in the genetic variability of A(H3N2) virus strains in southern Italy from 1999 to 2009. A partial sequence of the haemagglutinin (HA) gene by human influenza H3N2 strains identified in oropharyngeal swabs from patients with influenza-like illness was analysed by DNA sequencing and a phylogenetic analysis was performed. During the seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009, the influenza viruses circulating belonged to subtype H3N2. However, A(H1N1) subtype virus and B type were respectively prevalent during the 2000-2001, 2006-2007, 2007-2008 and 2001-2002, 2003-2004, 2005-2006 seasons. The HA sequences appeared to be closely related to the sequence of the influenza A vaccine strain. Only the 2002-2003 season was characterized by co-circulation of two viral lineages: A/New York/55/01(H3N2)-like virus of the previous season and A/Fujian/411/02(H3N2)-like virus, a new H3 variant. In this study, over the decade analysed, no significant change was seen in the sequences of the HA gene of H3 viruses isolated.

  18. The bond strength of adhesive resins to AH plus contaminated dentin cleaned by various gutta-percha solvents.

    PubMed

    Topçuoğlu, Hüseyin Sinan; Demirbuga, Sezer; Pala, Kansad; Cayabatmaz, Muhammed; Topçuoğlu, Gamze

    2015-01-01

    The optimal bonding of adhesives to dentin requires the sealer to be completely removed from dentinal walls. The aim of this study was to investigate the effect of different cleaning procedures using gutta-percha solvents on bond strength of adhesive resins to AH Plus contaminated dentin (APCD). The pulp chamber dentin surfaces were contaminated with AH Plus and cleaned with five different techniques (dry cotton, chloroform, orange oil, eucalyptol, and ethanol). Then, Clearfil SE Bond (CSE) (Kuraray), and Tetric N Bond (TNB) (Ivoclar Vivadent) were applied and filled with a composite resin. The serial sticks (1 × 1 mm) were obtained and tested for microtensile bond strength. Scanning electron microscopy (SEM) was used for analysis of debonded surfaces. Ethanol exhibited the highest bond strength to APCD followed by dry cotton. There was no statistically significant difference between ethanol and dry cotton (p > 0.05). Eucalyptol showed the lowest bond strength to APCD and statistically significant differences (p < 0.05) in comparison with other groups. APCD reduced the bond strength of all adhesive resins. Dry cotton, ethanol, and chloroform were the most suitable techniques when used with CSE together, whereas ethanol was best with TNB. PMID:25678408

  19. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    PubMed

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time.

  20. Formulation of stable Bacillus subtilis AH18 against temperature fluctuation with highly heat-resistant endospores and micropore inorganic carriers.

    PubMed

    Chung, Soohee; Lim, Hyung Mi; Kim, Sang-Dal

    2007-08-01

    To survive the commercial market and to achieve the desired effect of beneficial organisms, the strains in microbial products must be cost-effectively formulated to remain dormant and hence survive through high and low temperatures of the environment during transportation and storage. Dormancy and stability of Bacillus subtilis AH18 was achieved by producing endospores with enhanced heat resistance and using inorganic carriers. Heat stability assays, at 90 degrees C for 1 h, showed that spores produced under a sublethal temperature of 57 degrees C was 100 times more heat-resistant than the ones produced by food depletion at the growing temperature of 37 degrees C. When these highly heat-resistant endospores were formulated with inorganic carriers of natural and synthetic zeolite or kaolin clay minerals having substantial amount of micropores, the dormancy of the endospores was maintained for 6 months at 15-25 degrees C. Meanwhile, macroporous perlite carriers with average pore diameter larger than 3.7 microm stimulated the germination of the spores and rapid proliferation of the bacteria. These results indicated that a B. subtilis AH18 product that can remain dormant and survive through environmental temperature fluctuation can be formulated by producing heat-stressed endospores and incorporating inorganic carriers with micropores in the formulation step.

  1. Knowledge, attitudes and perceptions of health professionals in relation to A/H1N1 influenza and its vaccine

    PubMed Central

    López-Picado, Amanda; Apiñaniz, Antxon; Ramos, Amaia Latorre; Miranda-Serrano, Erika; Cobos, Raquel; Parraza-Díez, Naiara; Amezua, Patricia; Martinez-Cengotitabengoa, Mónica; Aizpuru, Felipe

    2012-01-01

    Objective To determine the intention of health professionals, doctors and nurses, concerning whether or not to be vaccinated against A/H1N1 influenza virus, and their perception of the severity of this pandemic compared with seasonal flu. Material and Methods A cross-sectional study was carried out based on an questionnaire e-mailed to health professionals in public healthcare centres in Vitoria between 6 and 16 November 2009; the percentage of respondents who wanted to be vaccinated and who perceived the pandemic flu to carry a high risk of death were calculated. Results A total of 115 people completed the questionnaire of whom 61.7% (n=71) were doctors and 38.3% (n=44) were nurses. Of these, 33.3% (n=23) of doctors and 13.6% (n=6) of nurses intended to be vaccinated (p=0.019). Even among those who considered themselves to be at a high risk, 70.6% (n=48) of doctors and 31.7% (n=13) of nurses participating in the study (p=0.001) planned to have the vaccination. Conclusions Most health professionals, and in particular nurses, had no intention to be vaccinated against A/H1N1 influenza virus at the beginning of the vaccination campaign. PMID:22461846

  2. Bacterial leakage of GuttaFlow-filled root canals compared with Resilon/Epiphany and Gutta-percha/AH26-filled root canals.

    PubMed

    Kangarlou, Ali; Dianat, Omid; Esfahrood, Zeinab Rezaei; Asharaf, Hengameh; Zandi, Babak; Eslami, Gita

    2012-04-01

    The purpose of this study was to assess bacterial apical leakage in root canals obturated with GuttaFlow and compare this with the leakage of root canals obturated with Resilon/Epiphany or Gutta-percha/AH26. A total of 55 single-rooted human teeth were divided randomly into three experimental (n = 15) and two control groups (n = 5). Following a standardised preparation, the teeth were obturated with either GuttaFlow, Resilon/Epiphany or Gutta-percha/AH26. A two-chamber bacterial model using Enterococcus faecalis was employed to assess bacterial apical leakage for a period of 60 days. A Kruskal-Wallis test showed no significant differences between the seal of root canals obturated with GuttaFlow, Resilon/Ephiphany or Gutta-percha/AH26. PMID:22432820

  3. Precursor systems analyses of automated highway systems. Activity area A. Urban and rural AHS comparison. Final report, September 1993-November 1994

    SciTech Connect

    Cochran, A.; Culver, B.; Halseth, M.; Hayes, S.; Mangarelli, F.

    1995-05-01

    This activity analyzes the technical and operational requirements of an AHS in urban and rural environments. The characteristics of urban freeways and rural highways are compared to define common issues and risks and indicate areas of divergence in compatible system implementations. The comparison addresses three major areas: the trade among the goals of automated control in urban versus rural environments; the distinct operating characteristics of AHS subsystems in rural highways; and the design considerations for several AHS-specific elements. The issues and risks concerning the most cost effective approach to instrumentation content in terms of the control loop dynamics and potential market penetration in both environments are identified. This document type is resource materials.

  4. The Discourse of Medicine in the Čahār Maqāla (Four Discourses) of Nezami Aruzi of Samarghand.

    PubMed

    Afshar, Ahmadreza

    2015-09-01

    Nezami Aruzi prepared Čahār Maqāla (Four Discourses) as a guide and admonishment for the rulers and kings. The fourth discourse of Čahār Maqāla with 12 anecdotes is devoted to the science of medicine and the characteristics of the physicians. The discourse presents the name of the eminent scientists, physicians, as well as Farsi and Arabic medical books that had professional acceptance in the medieval in Persia. The author has described how medicine was studied in the medieval in Persia and has presented notes on the physiology of the nervous system, pulse, uroscopy, fever, spiritual affairs and medical ethics. The current essay is a brief review of the medical subjects in Čahār Maqāla. PMID:26317607

  5. Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high-dose oseltamivir exposure.

    PubMed

    Watcharananan, S P; Suwatanapongched, T; Wacharawanichkul, P; Chantratitaya, W; Mavichak, V; Mossad, S B

    2010-04-01

    We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients. PMID:20102550

  6. 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.

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

    PubMed Central

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

    2015-01-01

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

  8. Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver

    SciTech Connect

    Qu Xiaoyu; Metz, Richard P.; Porter, Weston W.; Cassone, Vincent M.; Earnest, David J.

    2009-02-01

    The aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) are transcription factors that express Per-Arnt-Sim (PAS) DNA-binding motifs and mediate the metabolism of drugs and environmental toxins in the liver. Because these transcription factors interact with other PAS genes in molecular feedback loops forming the mammalian circadian clockworks, we determined whether targeted disruption or siRNA inhibition of Per1 and Per2 expression alters toxin-mediated regulation of the AhR signaling pathway in the mouse liver and Hepa1c1c7 hepatoma cells in vitro. Treatment with the prototypical Ahr ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), had inductive effects on the primary targets of AhR signaling, Cyp1A1 and Cyp1B1, in the liver of all animals, but genotype-based differences were evident such that the toxin-mediated induction of Cyp1A1 expression was significantly greater (2-fold) in mice with targeted disruption of Per1 (Per1{sup ldc} and Per1{sup ldc}/Per2{sup ldc}). In vitro experiments yielded similar results demonstrating that siRNA inhibition of Per1 significantly increases the TCDD-induced expression of Cyp1A1 and Cyp1B1 in Hepa1c1c7 cells. Per2 inhibition in siRNA-infected Hepa1c1c7 cells had the opposite effect and significantly decreased both the induction of these p450 genes as well as AhR and Arnt expression in response to TCDD treatment. These findings suggest that Per1 may play a distinctive role in modulating AhR-regulated responses to TCDD in the liver.

  9. 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

  10. DNA Mismatch Repair Interacts with CAF-1- and ASF1A-H3-H4-dependent Histone (H3-H4)2 Tetramer Deposition.

    PubMed

    Rodriges Blanko, Elena; Kadyrova, Lyudmila Y; Kadyrov, Farid A

    2016-04-22

    DNA mismatch repair (MMR) is required for the maintenance of genome stability and protection of humans from several types of cancer. Human MMR occurs in the chromatin environment, but little is known about the interactions between MMR and the chromatin environment. Previous research has suggested that MMR coincides with replication-coupled assembly of the newly synthesized DNA into nucleosomes. The first step in replication-coupled nucleosome assembly is CAF-1-dependent histone (H3-H4)2 tetramer deposition, a process that involves ASF1A-H3-H4 complex. In this work we used reconstituted human systems to investigate interactions between MMR and CAF-1- and ASF1A-H3-H4-dependent histone (H3-H4)2 tetramer deposition. We have found that MutSα inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mismatch into a tetrasome. This finding supports the idea that MMR occurs before the DNA mismatch is packaged into the tetrasome. Our experiments have also revealed that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers does not interfere with MMR reactions. In addition, we have established that unnecessary degradation of the discontinuous strand that takes place in both DNA polymerase δ (Pol δ)- and DNA polymerase ϵ (Pol ϵ)-dependent MMR reactions is suppressed by CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers. These data suggest that CAF-1- and ASF1A-H3-H4-dependent deposition of the histone (H3-H4)2 tetramers is compatible with MMR and protects the discontinuous daughter strand from unnecessary degradation by MMR machinery.

  11. Characterization of T cells and cytokines in the aqueous humour (AH) in patients with Fuchs' heterochromic cyclitis (FHC) and idiopathic anterior uveitis (IAU)

    PubMed Central

    Muhaya, M; Calder, V; Towler, H M A; Shaer, B; McLauchlan, M; Lightman, S

    1998-01-01

    FHC and IAU are two forms of anterior uveitis which are localized to the eyes with no evidence of systemic involvement. However, FHC has distinct clinical features and differs from IAU in that the inflammation is low grade, steroid non-responsive, and has a less aggressive clinical course. To try to dissect the mechanism for this difference the phenotypes of the cells in the AH and blood (PB) and the cytokines present in the AH in patients with FHC and IAU were compared. Three-colour flow cytometry was performed on the cells isolated from the AH and PB. Percentage of cells bearing the following markers were determined: CD3, CD4, CD8, CD4/CD25, CD8/CD25, CD19 and CD14. The cytokines IL-4, IL-10, IL-12 and interferon-gamma (IFN-γ) were assayed by ELISA. In both groups T cell numbers were higher in the AH than PB, although the distribution of T cell subsets in PB was similar. In the AH, CD8+ T cell numbers were higher in FHC than in IAU (P = 0·003), whilst CD4+ numbers were higher in IAU than FHC (P = 0·01). AH cytokine profiles were different in the two groups: IFN-γ levels were higher and IL-12 levels lower in the FHC group than IAU (P = 0·02), whilst IL-10 levels tended to be higher in the FHC group (P = 0·5). We suggest that different local mechanisms governing the balance of T cell/cytokine-mediated inflammation in the anterior segment may underlie clinical differences such as chronicity and response to steroids in these disorders. PMID:9472671

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

    PubMed

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

    2015-01-01

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

  13. 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.

  14. 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.

  15. Epidemiological Characterization of Influenza A(H1N1)pdm09 Cases from 2009 to 2010 in Baguio City, the Philippines

    PubMed Central

    Pamaran, Rochelle R.; Kamigaki, Taro; Hewe, Teresita T.; Flores, Korrine Madeleine C.; Mercado, Edelwisa S.; Alday, Portia P.; Tan, Alvin G.; Oshitani, Hitoshi; Olveda, Remigio M.; Tallo, Veronica L.

    2013-01-01

    Background Baguio City, Philippines experienced its first influenza A(H1N1)pdm09 [A(H1)pdm09] case in May 2009. In spite of numerous reports describing the epidemiological and clinical features of A(H1)pdm09 cases, there are no studies about A(H1)pdm09 epidemiology in the Philippines, where year-round influenza activity was observed. Objectives We aimed to investigate the epidemiological and clinical features of A(H1)pdm09 in pandemic and post-pandemic periods. Methods Data were collected under enhanced surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) from January 2009 to December 2010. RT-PCR was used to detect A(H1)pdm09, following the protocol of the United States Centers for Disease Control and Prevention. The reproduction number was computed as a simple exponential growth rate. Differences in proportional and categorical data were examined using chi-square test or Fishers’ exact test. Results and Conclusions The outbreak was observed from week 25 to 35 in 2009 and from week 24 to 37 in 2010. The highest proportion of cases was among children aged 5–14 years. The number of ILI outpatients was 2.3-fold higher in 2009 than in 2010, while the number of inpatients was 1.8-fold higher in 2009. No significant difference in gender was observed during the two periods. The clinical condition of all patients was generally mild and self-limiting, with only 2 mortalities among inpatients in 2009. The basic reproduction number was estimated as 1.16 in 2009 and 1.05 in 2010 in the assumption of mean generation time as 2.6 days. School children played a significant role in facilitating influenza transmission. PMID:24244578

  16. Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats

    PubMed Central

    Wu, Di; Yin, Lei; Fan, Yao; Wang, Ye; Chen, Wei-Ran; Chen, Pei; Liu, Yang; Lu, Xiao-Long; Sun, Hong-Li; Shou, Weinian; Qiao, Guo-Fen; Li, Bai-Yan

    2015-01-01

    Background Ketamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated. Methods Action potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated. Results Ketamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ∼50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types). Conclusions These data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway. PMID:26675761

  17. Epidemiological Characterization of a Fourth Wave of Pandemic A/H1N1 Influenza in Mexico, Winter 2011–2012: Age Shift and Severity

    PubMed Central

    Borja-Aburto, Víctor H.; Chowell, Gerardo; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Grajales-Muñiz, Concepción; González-Bonilla, Cesar R.; Diaz-Quiñonez, Jose A; Echevarría-Zuno, Santiago

    2012-01-01

    Background and Aims A substantial recrudescent wave of pandemic influenza A/H1N1 affected the Mexican population from December 1, 2011–March 20, 2012 following a 2-year period of sporadic transmission. Methods We analyzed demographic and geographic data on all hospitalizations with severe acute respiratory infection (SARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by a Mexican social security medical system during April 1, 2009– March 20, 2012. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset. Results A total of 7569 SARI hospitalizations and 443 in-patient deaths (5.9%) were reported between December 1, 2011, and March 20, 2012 (1115 A/H1N1-positive inpatients and 154 A/H1N1-positive deaths). The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among subjects ≥60 years of age (χ2 test, p <0.0001) and lower among younger age groups (χ2 test, p <0.04) for the 2011–2012 pandemic wave compared to the earlier waves in 2009. The reproduction number of the winter 2011–2012 wave in central Mexico was estimated at 1.2–1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009. Conclusions We documented a substantial increase in the number of SARI hospitalizations during the period December 2011–March 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is consistent with a build-up of immunity among younger populations. PMID:23079035

  18. Precursor systems analyses of automated highway systems. Activity area H: AHS roadway deployment analysis. Resource materials. Final report, September 1993-November 1994

    SciTech Connect

    Bruggeman, D.; Markovetz, S.

    1996-01-01

    The objective of this analysis is to identify the issues and risks related to the deployment of the automated highway system (AHS) in urban and rural operating environments, from the perspective of impacts on the roadway for each of the representative system configurations (RSC). The purpose of this effort is to identify and evaluate the various issues and risks and to determine if a mitigation strategy can be identified that addreses the negative implications to a level that makes AHS deployment successful in a variety of operating environments when applied to the RSCs.

  19. 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

  20. [Fatal pneumonitis due to oseltamivir-resistant new influenza A(H1N1) in the case of an intensive care patient].

    PubMed

    Aardema, Heleen; Tulleken, Jaap E; van den Biggelaar, Ries J M; Wolters, Bert A; de Jager, Corine M; Boucher, Charles A B; Riezebos-Brilman, Annelies

    2010-01-01

    A 58-year-old man was submitted to our intensive care ward with respiratory failure due to pneumonitis. He had previously been treated for non-Hodgkin lymphoma by autologous stem cell transplantation, as a result of which bone marrow function was reduced. Further analysis showed infection with new influenza A(H1N1); typing revealed an oseltamivir-resistant subpopulation (H275Y). The patient was treated with oseltamivir and intravenously with zanamivir, but died of respiratory disease progression. This is the first published case of oseltamivir-resistant new influenza A(H1N1) infection in the Netherlands. PMID:20482913

  1. An Invitro Evaluation of Antimicrobial Efficacy and Flow Characteristics for AH Plus, MTA Fillapex, CRCS and Gutta Flow 2 Root Canal Sealer

    PubMed Central

    Gupta, Prashant; Tikku, Aseem P; Pathak, Anjani Kumar; Chandra, Anil; Yadav, Rakesh Kumar; Bharti, Ramesh; Singh, Rajeev Kumar

    2016-01-01

    Introduction Cleaning and shaping of root canal does not guarantee complete disinfection of the canal, regardless of the systems and techniques used for this purpose. Therefore, it becomes mandatory for the endodontic filling materials to have a good antimicrobial potential especially against E. faecalis. This research was aimed therefore to evaluate the antibacterial efficacy and flow properties of different root canal sealers. Aim To study invitro antimicrobial activity and flow characteristics for Resin based (AH Plus), Mineral Trioxide Aggregate based (MTA Fillapex), Calcium hydroxide based (CRCS) and Flowable Gutta-Percha (Gutta Flow 2) endodontic sealers on Enterococcus faecalis. Materials and Methods Enterococcus faecalis ATCC 29212 was used to test antibacterial potential of sealers by Agar diffusion test (ADT) and Direct Contact Test (DCT). ADT was performed by punching the sealers on a well of 4×6mm diameter on Muller Hinton agar plates. These plates were inoculated with standard suspension of E. faecalis and the zone of inhibition was measured at 24 hours and after 7 days. All the sealers were prepared in accordance with the manufacturer’s recommendations. Flow of sealers was measured according to ADA specification no. 57. Results All sealers showed antibacterial activity against E. faecalis except Gutta Flow 2. At 24 hours, zone of inhibition was highest in Calcibiotic Root Canal Sealer (CRCS) and lowest in AH Plus. After 7 days the zone of inhibition decreased in AH plus, CRCS and MTA Fillapex. DCT showed a significant lower number of organisms in AH Plus, CRCS and MTA than controls at both the time intervals. Gutta Flow 2 did not show any significant antimicrobial action. Maximum and minimum flow was shown by AH Plus and CRCS respectively. Conclusion Highest microbial inhibition was shown by (CRCS), followed by MTA Fillapex and AH Plus. Gutta Flow 2 did not show any inhibition of E. faecalis by ADT. Maximum reduction in antibacterial property with

  2. Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

    PubMed Central

    Casado, Itziar; Martínez-Baz, Iván; Burgui, Rosana; Irisarri, Fátima; Arriazu, Maite; Elía, Fernando; Navascués, Ana; Ezpeleta, Carmen; Aldaz, Pablo; Castilla, Jesús

    2014-01-01

    Background The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. Methods During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. Results In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03). Conclusion The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons. PMID:25254376

  3. Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

    PubMed Central

    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.

    2015-01-01

    Summary 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

  4. Socioeconomic Factors Influencing Hospitalized Patients with Pneumonia Due to Influenza A(H1N1)pdm09 in Mexico

    PubMed Central

    Manabe, Toshie; Higuera Iglesias, Anjarath Lorena; Vazquez Manriquez, Maria Eugenia; Martinez Valadez, Eduarda Leticia; Ramos, Leticia Alfaro; Izumi, Shinyu; Takasaki, Jin; Kudo, Koichiro

    2012-01-01

    Background In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. Methodology and Principal Findings A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. Conclusions Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These

  5. Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

    PubMed

    Feldstein, Leora R; Matrajt, Laura; Elizabeth Halloran, M; Keitel, Wendy A; Longini, Ira M

    2016-07-19

    Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals

  6. Qualification Testing of General Electric 50 Ah Nickel-Cadmium Cells with New Separator and New Positive Plate Processing

    NASA Technical Reports Server (NTRS)

    Morrow, G. W.

    1986-01-01

    Forty-two 50 Ah aerospace nickel-cadmium cells were delivered to Goddard Space Flight Center (GSFC) by General Electric (GE) in February, 1985, for the purpose of evaluating and qualifying a new nylon separator material Pellon 2536, and the new GE Positive Plate Nickel Attack Control Passivation process. Testing began in May, 1985, at the Naval Weapons Support Center (NWSC) in Crane, Indiana with standard initial evaluation tests. Life cycling in both Low Earth Orbit (LEO) and Geosynchronous Orbit (GEO) began in July, 1985, with approximately 1200 LEO cycles complete at this writting. Early test results show that cells with positive plate passivation exhibit higher than normal charge voltage characteristics. Other aspects of performance were nominal.

  7. Qualification testing of General Electric 50 Ah nickel-cadmium cells with Pellon 2536 separator and passivated positive plates

    NASA Technical Reports Server (NTRS)

    Morrow, George W.

    1987-01-01

    Forty-two 50 Ah nickel-cadmium cells were delivered to the Goddard Space Flight Center (GSFC) by General Electric (GE) in February, 1985 for the purpose of evaluating and qualifying a nonwoven nylon separator material, Pellon 2536, and the GE positive plate nickel attack control gas passivation process. Testing began May, 1985 at the Naval Weapons Support Center (NWSC) in Crane, Indiana with GSFC standard initial evaluation tests. Life cycling in both Low Earth Orbit (LEO) and Geosynchronous Orbit (GEO) began in July, 1985 with approximately 6500 LEO cycles and three GEO eclipse seasons completed. After early problems in maintaining test pack temperature control, all packs are performing well but are exhibiting higher than normal charge voltage characteristics.

  8. Comparison of root canal filling quality by mineral trioxide aggregate and gutta percha cones/AH plus sealer.

    PubMed

    Jho, Wonkyung; Park, Jeong-Won; Kim, Euiseong; Song, Minju; Seo, Deok-Gyu; Yang, Dong-Kyu; Shin, Su-Jung

    2016-01-01

    The aims of this study were to evaluate the quality of canal filling using mineral trioxide aggregate (MTA) and gutta-percha (GP) in root canals, and to investigate the differences in the percentage of voids between mesial and distal canals by using microcomputed tomography. Twenty-two extracted human mandibular molars were instrumented using rotary files. Two teeth without canal fillings served as negative controls, and the other teeth were obturated with either ProRoot(®) MTA or gutta-percha and AH Plus(®) sealer. Obturated teeth were scanned with microcomputed tomography, and the percentage of voids (V%) was calculated. These specimens were also examined under a scanning electron microscope. The MTA group showed a significantly higher V% than the GP groups (p<0.05). The mesial canal groups showed significantly higher V% than did the distal canal groups (p<0.05). In orthograde filling, MTA exhibited significantly lower filling quality than did GP.

  9. [Influenza A/H1N1 pandemic: central European experience and perspective of prevention and control of this disease].

    PubMed

    Snacken, R

    2009-01-01

    When the influenza pandemic A/H1N1 emerged in 2009, European countries activated their national pandemic plan that were initiated in 2005 when ECDC was established in Stockholm. This agency from the European Commission played its role to strengthen capacities of Member States. ECDC essentially focused attention on surveillance and its reinforcement, epidemic intelligence and guidance. Nevertheless, main challenges remain to be met: continuous adjustment of assumptions, weaknesses in national plans (e.g. no stockpile of antibiotics), paucity of investment in scientific research, no control of transmission from human to animal, persistence of the impact of the pandemic in the subsequent years and eventually the worrying unpreparedness of developing countries that paid a huge toll during previous pandemics.

  10. Comparison of biological and physical properties of human and animal A(H1N1) influenza viruses.

    PubMed

    Fiszon, B; Hannoun, C; Garcia-Sastre, A; Villar, E; Cabezas, J A

    1989-01-01

    The study of biological properties of influenza virus strains belonging to the same subtype A(H1N1) and closely antigenically related, but isolated from different animal species (man, pig and duck), demonstrated that avian strains were more resistant than those isolated from mammals to high temperature and low pH, as shown by titration of residual infectivity in cell cultures (MDCK) and by sialidase assay. The difference in behaviour could be correlated to biological adaptation of the virus to its host. Avian body temperature is 40 degrees C and influenza virus, in ducks, is enterotropic and therefore capable of passing through the low pH values in the upper digestive tract of the animal. These results do not contradict the hypothesis of a possible filiation between avian and mammalian orthomyxoviruses.

  11. Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

    PubMed Central

    2011-01-01

    Background Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement. PMID:22206235

  12. New Influenza A/H1N1 (“Swine Flu”): information needs of airport passengers and staff

    PubMed Central

    Dickmann, P.; Rubin, G. J.; Gaber, W.; Wessely, S.; Wicker, S.; Serve, H.; Gottschalk, R.

    2010-01-01

    Please cite this paper as: Dickmann et al. (2010) New Influenza A/H1N1 (“Swine Flu”): information needs of airport passengers and staff. . Influenza and Other Respiratory Viruses 5(1), 39–46. Background  Airports are the entrances of infectious diseases. Particularly at the beginning of an outbreak, information and communication play an important role to enable the early detection of signs or symptoms and to encourage passengers to adopt appropriate preventive behaviour to limit the spread of the disease. Objectives  To determine the adequacy of the information provided to airport passengers and staff in meeting their information needs in relation to their concerns. Methods  At the start of the influenza A/H1N1 epidemic (29–30 April 2009), qualitative semi‐structured interviews (N = 101) were conducted at Frankfurt International Airport with passengers who were either returning from or going to Mexico and with airport staff who had close contact with these passengers. Interviews focused on knowledge about swine flu, information needs and fear or concern about the outbreak. Results  The results showed that a desire for more information was associated with higher concern – the least concerned participants did not want any additional information, while the most concerned participants reported a range of information needs. Airport staff in contact with passengers travelling from the epicentre of the outbreak showed the highest levels of fear or concern, coupled with a desire to be adequately briefed by their employer. Conclusions  Our results suggest that information strategies should address not only the exposed or potentially exposed but also groups that feel at risk. Identifying what information these different passenger and staff groups wish to receive will be an important task in any future infectious disease outbreak. PMID:21138539

  13. Determinants of Refusal of A/H1N1 Pandemic Vaccination in a High Risk Population: A Qualitative Approach

    PubMed Central

    d'Alessandro, Eugenie; Hubert, Dominique; Launay, Odile; Bassinet, Laurence; Lortholary, Olivier; Jaffre, Yannick; Sermet-Gaudelus, Isabelle

    2012-01-01

    Background Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine. Methodology/Principal Findings We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu's potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider. Conclusions/Significance These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization. PMID:22506011

  14. Overview of the winter wave of 2009 pandemic influenza A(H1N1)v in Vojvodina, Serbia

    PubMed Central

    Petrović, Vladimir; Šeguljev, Zorica; Ćosić, Gorana; Ristić, Mioljub; Nedeljković, Jasminka; Dragnić, Nataša; Ukropina, Snežana

    2011-01-01

    Aim To analyze the epidemiological data for pandemic influenza A(H1N1)v in the Autonomous Province of Vojvodina, Serbia, during the season of 2009/2010 and to assess whether including severe acute respiratory illness (SARI) hospitalization data to the surveillance system gives a more complete picture of the impact of influenza during the pandemic. Methods From September 2009 to September 2010, the Institute of Public Health of Vojvodina conducted sentinel surveillance of influenza-like illnesses and acute respiratory infections in all hospitalized patients with SARI and virological surveillance of population of Vojvodina according to the European Centers for Disease Control technical document. Results The pandemic influenza outbreak in the province started in October 2009 (week 44) in students who had returned from a school-organized trip to Prague, Bratislava, and Vienna. The highest incidence rate was 1090 per 100 000 inhabitants, found in the week 50. The most affected age group were children 5-14 years old. A total of 1591 patients with severe illness were admitted to regional hospitals, with a case fatality rate of 2%, representing a hospitalization rate of 78.3 per 100 000 inhabitants and a mortality rate of 1.6 per 100 000. Most frequently hospitalized were 15-19 years old patients, male patients, and patients with pneumonia (P < 0.001). The highest case fatality rate was found among patients with acute respiratory distress syndrome (P < 0.001). Nasal/throat swabs were obtained for polymerase chain reaction test from 315 hospitalized patients and 20 non-hospitalized patients, and 145 (46%) and 15 (75%) specimens, respectively, tested positive on A(H1N1)v. Conclusion Sentinel influenza-like illness and SARI surveillance, both followed with virological surveillance, seem to be the optimal method to monitor the full scope of the influenza pandemic (from mild to severe influenza) in Vojvodina. PMID:21495196

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

    PubMed

    Epperson, Scott; Jhung, Michael; Richards, Shawn; Quinlisk, Patricia; Ball, Lauren; Moll, Mària; Boulton, Rachelle; Haddy, Loretta; Biggerstaff, Matthew; Brammer, Lynnette; Trock, Susan; Burns, Erin; Gomez, Thomas; Wong, Karen K; Katz, Jackie; Lindstrom, Stephen; Klimov, Alexander; Bresee, Joseph S; Jernigan, Daniel B; Cox, Nancy; Finelli, Lyn

    2013-07-01

    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(H1N1)pdm09 pandemic influenza virus. METHODS. A case was defined as a person with laboratory-confirmed H3N2v virus infection. Cases and contacts were interviewed to determine exposure to swine and other animals and to assess potential person-to-person transmission. RESULTS. Median age of cases was 4 years, and 12 of 13 (92%) were children. Pig exposure was identified in 7 (54%) cases. Six of 7 cases with swine exposure (86%) touched pigs, and 1 (14%) was close to pigs without known direct contact. Six cases had no swine exposure, including 2 clusters of suspected person-to-person transmission. All cases had fever; 12 (92%) had respiratory symptoms, and 3 (23%) were hospitalized for influenza. All 13 cases recovered. CONCLUSIONS. H3N2v virus infections were identified at a high rate from August 2011 to April 2012, and cases without swine exposure were identified in influenza-like illness outbreaks, indicating that limited person-to-person transmission likely occurred. Variant influenza viruses rarely result in sustained person-to-person transmission; however, the potential for this H3N2v virus to transmit efficiently is of concern. With minimal preexisting immunity in children and the limited cross-protective effect from seasonal influenza vaccine, the majority of children are susceptible to infection with this novel influenza virus.

  16. Highly pathogenic avian influenza A(H5N8) viruses reintroduced into South Korea by migratory waterfowl, 2014–2015

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza A(H5N8) viruses were isolated from migratory waterfowl in South Korea during all 2014–winter 2015, a recurrence after initial introduction in winter 2014. These reappeared viruses were phylogenetically distinct from isolates circulating in poultry farms in South Kor...

  17. Application of a Comprehensive Analytical Model of Rotor Aerodynamics and Dynamics (CAMRAD) to the McDonnell Douglas AH-64A helicopter

    NASA Technical Reports Server (NTRS)

    Callahan, Cynthia B.; Bassett, Duane E.

    1988-01-01

    A model of the AH-64A helicopter was generated in a Comprehensive Analytical Model of Rotorcraft Aerodynamics and Dynamics (CAMRAD) in an effort to validate its analytical capabilities for modeling a current advanced Army helicopter. The initial phase of the effort involved the generation of CAMRAD input files necessary for the complete aerodynamic, structural, and dynamic definition of the production AH-64A helicopter. The input files were checked by making comparisons of CAMRAD full helicopter trim and main rotor blade natural frequency predictions with those of full helicopter trim program, Blade Element Trim (BETRIM), and dynamic analysis code, Dynamic Analysis Research Tool (DART), respectively. The main thrust concerned the application of the AH-64A CAMRAD model thus developed and verified for main rotor blade structural loads predictions and comparison with DART analytical results. The investigation provided insight not only into the usefulness of CAMRAD for the AH-64A performance and dynamics prediction, but also into the limitations of the program for modeling advanced rotor and fuselage systems. The model development effort is discussed, the results of the CAMRAD correlation studies presented, and some general conclusions are offered on the applicability of CAMRAD for rotor aeroelastic loads prediction for current and future rotorcraft configurations.

  18. Highly Pathogenic Avian Influenza A(H5N8) Viruses Reintroduced into South Korea by Migratory Waterfowl, 2014–2015

    PubMed Central

    Kwon, Jung-Hoon; Lee, Dong-Hun; Swayne, David E.; Noh, Jin-Yong; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Hong, Woo-Tack; Jeong, Jei-Hyun; Jeong, Sol; Gwon, Gyeong-Bin

    2016-01-01

    Highly pathogenic avian influenza A(H5N8) viruses were isolated from migratory waterfowl in South Korea during fall 2014–winter 2015, a recurrence after initial introduction in winter 2014. These reappeared viruses were phylogenetically distinct from isolates circulating in poultry farms in South Korea. PMID:26890406

  19. 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.

  20. Full-Genome Sequence of Influenza A(H5N8) Virus in Poultry Linked to Sequences of Strains from Asia, the Netherlands, 2014.

    PubMed

    Bouwstra, Ruth; Heutink, Rene; Bossers, Alex; Harders, Frank; Koch, Guus; Elbers, Armin

    2015-05-01

    Genetic analyses of highly pathogenic avian influenza A(H5N8) virus from the Netherlands, and comparison with strains from Europe, South Korea, and Japan, showed a close relation. Data suggest the strains were probably carried to the Netherlands by migratory wild birds from Asia, possibly through overlapping flyways and common breeding sites in Siberia.

  1. Precursor systems analyses of automated highway systems. Activity area A. Urban and rural AHS comparisons. Final report, September 1993-November 1994

    SciTech Connect

    Chatziioanou, A.

    1995-06-01

    Several potential AHS operating mode alternatives were developed through `representative system configurations` and operating concept variable combinations. Alternatives are mapped in the `Operating Mode Input Matrix` and grouped in four basic stages of development. System overall performance was assessed. Discussion on the impacts of differences in the evaluation of urban and rural settings follow. Representative System Configuration variables include guideway separation, heavy vehicle handling and intelligence/authority distribution while operating variables include vehicle spacing, speed and demand levels. Theoretical capacity, safety and environmental impact as it applies to air quality are addressed for the operating modes analyzed. Assessments were made by partitioning of the initial questions in subsets of issues. Every group eventually tries to focus its investigation to the differences and similarities between urban and rural AHS deployments as viewed through the prism of the group-specific issues. Overall it seems that urban and rural AHS deployments could work in parallel. Special attention needs to be given during the stage of separate AHS infrastructure development for compatibility with previous stages.

  2. Transmission by super-spreading event of pandemic A/H1N1 2009 influenza during road and train travel.

    PubMed

    Pestre, Vincent; Morel, Bruno; Encrenaz, Nathalie; Brunon, Amandine; Lucht, Frédéric; Pozzetto, Bruno; Berthelot, Philippe

    2012-03-01

    The investigation of clustered cases of pandemic A/H1N1 2009 influenza virus infection (21 children, 3 adults) during a summer camp, led to the identification of transportation as the circumstance of transmission. Results suggest that super-spreading of flu can occur in a confined space without sufficient air renewal.

  3. 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. PMID:26658347

  4. Dietary supplementation of Bifidobacterium longum strain AH1206 increases its cecal abundance and elevates intestinal interleukin-10 expression in the neonatal piglet.

    PubMed

    Herfel, Tina M; Jacobi, Sheila K; Lin, Xi; Jouni, Zeina E; Chichlowski, Maciej; Stahl, Chad H; Odle, Jack

    2013-10-01

    Intestinal microbiota of infants differ in response to gestational age, delivery mode and feeding regimen. Dietary supplementation of probiotic bacteria is one method of promoting healthy populations. We examined the impact of a novel probiotic strain of Bifidobacterium longum (AH1206) on the health, growth and development of neonatal pigs as a model for infants. Day-old pigs were fed milk-based formula containing AH1206 at 0, 10⁹, or 10¹¹ CFU/d for 18 d (n=10/treatment). Differences were not detected in growth, organ weights or body temperatures (P>0.1); however pigs fed the high dose showed a small (2%) reduction in feed intake. Bacterial translocation was not affected as indicated by total anaerobic and aerobic counts (CFU) in samples of spleen, liver and mesenteric lymph nodes (P>0.1). Feeding AH1206 had no effects on fecal consistency, but increased the density of B. longum in the cecum. Ileal TNF expression tended to increase (P=0.08) while IL-10 expression increased linearly (P=0.01) with supplementation. Based upon findings in the suckling piglet model, we suggest that dietary supplementation with B. longum (AH1206) may be safe for human infants based on a lack of growth, development or deleterious immune-related effects observed in piglets. PMID:23872134

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25897841

  6. Seroprevalence of Antibodies against Seal Influenza A(H10N7) Virus in Harbor Seals and Gray Seals from the Netherlands

    PubMed Central

    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. PMID:26658347

  7. Performance of the Directigen EZ Flu A+B rapid influenza diagnostic test to detect pandemic influenza A/H1N1 2009.

    PubMed

    Boyanton, Bobby L; Almradi, Amro; Mehta, Tejal; Robinson-Dunn, Barbara

    2014-04-01

    The Directigen EZ Flu A+B rapid influenza diagnostic test, as compared to real-time reverse transcriptase polymerase chain reaction, demonstrated suboptimal performance to detect pandemic influenza A/H1N1 2009. Age- and viral load-stratified test sensitivity ranged from 33.3 to 84.6% and 0 to 100%, respectively.

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

    PubMed

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

    2013-05-01

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

  9. 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.

  10. 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.

  11. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

    PubMed

    Chambers, Catharine; Skowronski, Danuta M; Sabaiduc, Suzana; Winter, Anne Luise; Dickinson, James A; De Serres, Gaston; Gubbay, Jonathan B; Drews, Steven J; Martineau, Christine; Eshaghi, Alireza; Krajden, Mel; Bastien, Nathalie; Li, Yan

    2016-01-01

    Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses. PMID:27020673

  12. 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.

  13. High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity

    PubMed Central

    Matsuoka, Toshihiko; Sato, Tomoki; Akita, Tomoyuki; Yanagida, Jiturou; Ohge, Hiroki; Kuwabara, Masao; Tanaka, Junko

    2016-01-01

    The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13–2.23) and the VE was 43.9% (CI: 42.8–44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak. PMID:27763532

  14. 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. PMID:26917362

  15. A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic

    PubMed Central

    Veguilla, Vic; López-Gatell, Hugo; López-Martínez, Irma; Aparicio-Antonio, Rodrigo; Barrera-Badillo, Gisela; Rojo-Medina, Julieta; Gross, Felicia Liaini; Jefferson, Stacie N.; Katz, Jacqueline M.; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.

    2016-01-01

    Background The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors. Methods We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005–2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population. Results Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI. Conclusions Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011–2012 and

  16. 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).

  17. Mortality, Severe Acute Respiratory Infection, and Influenza-Like Illness Associated with Influenza A(H1N1)pdm09 in Argentina, 2009

    PubMed Central

    Azziz-Baumgartner, Eduardo; Cabrera, Ana María; Chang, Loretta; Calli, Rogelio; Kusznierz, Gabriela; Baez, Clarisa; Yedlin, Pablo; Zamora, Ana María; Cuezzo, Romina; Sarrouf, Elena Beatriz; Uboldi, Andrea; Herrmann, Juan; Zerbini, Elsa; Uez, Osvaldo; Rico Cordeiro, Pedro Osvaldo; Chavez, Pollyanna; Han, George; Antman, Julián; Coronado, Fatima; Bresee, Joseph; Kosacoff, Marina; Widdowson, Marc-Alain; Echenique, Horacio

    2012-01-01

    Introduction While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America. Methods During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI) in three sentinel cities. A proportion of case-patients provided swabs for influenza testing. We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive. We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event. Results We estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥65 years. Influenza A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45–64 years. While 9 (53%) of 17 influenza A(H1N1)pdm09 decedents with available data had obesity and 7 (17%) of 40 had diabetes, less than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing conditions (p≤0.001). Conclusion Influenza A(H1N1)pdm09 caused a similar burden of disease in Argentina as in other countries. Such disease burden suggests the potential value of timely influenza vaccinations. PMID:23118877

  18. Mechanosensory S-neurons rather than AH-neurons appear to generate a rhythmic motor pattern in guinea-pig distal colon

    PubMed Central

    Spencer, Nick J; Smith, Terence K

    2004-01-01

    Simultaneous intracellular recordings were made from myenteric neurons and circular muscle (CM) cells in isolated, stretched segments of guinea-pig distal colon. We have shown previously that maintained stretch generates a repetitive and coordinated discharge of ascending excitatory and descending inhibitory neuronal reflex pathways in the distal colon. In the presence of nifedipine (1–2 μm) to paralyse the muscle, simultaneous recordings were made from 25 pairs of AH (after-hyperpolarization)-neurons and CM cells separated by 100–500 μm. In all 25 AH-neurons, proximal process potentials (PPPs) were never recorded, even though at the same time, all recordings from neighbouring CM cells showed an ongoing discharge of inhibitory junction potentials (IJPs) anally, or excitatory junction potentials (EJPs) orally. In fact, 24 of 25 AH-neurons were totally silent, while in one AH-cell, some spontaneous fast excitatory postsynaptic potentials (FEPSPs) were recorded. All 10 electrically silent AH-cells that were injected with neurobiotin were found to be multipolar Dogiel type II neurons. In contrast, when recordings were made from myenteric S-neurons, two distinct electrical patterns of electrical activity were recorded. Recordings from 25 of 48 S-neurons showed spontaneous FEPSPs, the majority of which (22 of 25) showed periods when discrete clusters of FEPSPs (mean duration 88 ms) could be temporally correlated with the onset of EJPs or anal IJPs in the CM. Nine S-neurons were electrically quiescent. The second distinct electrical pattern in 14 S-neurons consisted of bursts, or prolonged trains of action potentials, which could be reduced to proximal process potentials (PPPs) in six of these 14 neurons during membrane hyperpolarization. Unlike FEPSPs, PPPs were resistant to a low Ca2+ –high Mg2+ solution and did not change in amplitude during hyperpolarizing pulses. Mechanosensory S-neurons were found to be uniaxonal or pseudounipolar filamentous neurons, with

  19. Aryl hydrocarbon receptor (AhR) inducers and estrogen receptor (ER) activities in surface sediments of Three Gorges Reservoir, China evaluated with in vitro cell bioassays.

    PubMed

    Wang, Jingxian; Bovee, Toine F H; Bi, Yonghong; Bernhöft, Silke; Schramm, Karl-Werner

    2014-02-01

    Two types of biological tests were employed for monitoring the toxicological profile of sediment cores in the Three Gorges Reservoir (TGR), China. In the present study, sediments collected in June 2010 from TGR were analyzed for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated activities. The estrogenic activity was assessed using a rapid yeast estrogen bioassay, based on the expression of a green fluorescent reporter protein. Weak anti-estrogenic activity was detected in sediments from an area close to the dam of the reservoir, and weak estrogenic activities ranging from 0.3 to 1 ng 17β-estradiol (E2) equivalents (EQ) g(-1) dry weight sediment (dw) were detected in sediments from the Wanzhou to Guojiaba areas. In the upstream areas Wanzhou and Wushan, sediments demonstrated additive effects in co-administration of 1 nM E2 in the yeast test system, while sediments from the downstream Badong and Guojiaba areas showed estrogenic activities which seemed to be more than additive (synergistic activity). There was an increasing tendency in estrogenic activity from upstream of TGR to downstream, while this tendency terminated and converted into anti-estrogenic activity in the area close to the dam. The AhR activity was detected employing rat hepatoma cell line (H4IIE). EROD activities were found homogenously distributed in sediments in TGR ranging from 200 to 311 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) EQ g(-1) dw for total AhR agonists and from 45 to 76 pg TCDD EQ g(-1) dw for more persistent AhR agonists. The known AhR agonists polycyclic aromatic hydrocarbon, polychlorinated biphenyl, and PCDD/F only explained up to 8 % of the more persistent AhR agonist activity in the samples, which suggests that unidentified AhR-active compounds represented a great proportion of the TCDD EQ in sediments from TGR. These findings of estrogenic potential and dioxin-like activity in TGR sediments provide possible weight-of-evidence of potential

  20. Aryl hydrocarbon receptor (AhR) inducers and estrogen receptor (ER) activities in surface sediments of Three Gorges Reservoir, China evaluated with in vitro cell bioassays.

    PubMed

    Wang, Jingxian; Bovee, Toine F H; Bi, Yonghong; Bernhöft, Silke; Schramm, Karl-Werner

    2014-02-01

    Two types of biological tests were employed for monitoring the toxicological profile of sediment cores in the Three Gorges Reservoir (TGR), China. In the present study, sediments collected in June 2010 from TGR were analyzed for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated activities. The estrogenic activity was assessed using a rapid yeast estrogen bioassay, based on the expression of a green fluorescent reporter protein. Weak anti-estrogenic activity was detected in sediments from an area close to the dam of the reservoir, and weak estrogenic activities ranging from 0.3 to 1 ng 17β-estradiol (E2) equivalents (EQ) g(-1) dry weight sediment (dw) were detected in sediments from the Wanzhou to Guojiaba areas. In the upstream areas Wanzhou and Wushan, sediments demonstrated additive effects in co-administration of 1 nM E2 in the yeast test system, while sediments from the downstream Badong and Guojiaba areas showed estrogenic activities which seemed to be more than additive (synergistic activity). There was an increasing tendency in estrogenic activity from upstream of TGR to downstream, while this tendency terminated and converted into anti-estrogenic activity in the area close to the dam. The AhR activity was detected employing rat hepatoma cell line (H4IIE). EROD activities were found homogenously distributed in sediments in TGR ranging from 200 to 311 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) EQ g(-1) dw for total AhR agonists and from 45 to 76 pg TCDD EQ g(-1) dw for more persistent AhR agonists. The known AhR agonists polycyclic aromatic hydrocarbon, polychlorinated biphenyl, and PCDD/F only explained up to 8 % of the more persistent AhR agonist activity in the samples, which suggests that unidentified AhR-active compounds represented a great proportion of the TCDD EQ in sediments from TGR. These findings of estrogenic potential and dioxin-like activity in TGR sediments provide possible weight-of-evidence of potential

  1. Sudden death of a patient with pandemic influenza (A/H1N1pdm) virus infection by acute respiratory distress syndrome.

    PubMed

    Takiyama, Akihiro; Wang, Lei; Tanino, Mishie; Kimura, Taichi; Kawagishi, Naoki; Kunieda, Yasuyuki; Katano, Harutaka; Nakajima, Noriko; Hasegawa, Hideki; Takagi, Tomoyuki; Nishihara, Hiroshi; Sata, Tetsutaro; Tanaka, Shinya

    2010-01-01

    We describe an autopsy case of a patient with pandemic influenza (A/H1N1pdm) virus infection in Japan, who developed rapidly progressive viral pneumonia exhibiting diffuse alveolar damage. A 41-year-old female visited our hospital with a fever of 38.7C. She was a public health nurse with no underlying disease and had had contact with a group of elementary school students who had been infected with the influenza (A/H1N1pdm) virus 1 week earlier. She was prescribed oseltamivir and returned to the hotel where she was staying alone. The next day, she was found dead in her hotel room. At autopsy, both lungs were voluminous and microscopic examination revealed acute-stage, severe diffuse alveolar damage with remarkable mononuclear cell infiltration and hyaline membrane formation in the lungs. CD8-positive T lymphocytes were dominantly observed. Immunohistochemically, influenza A viral protein was confirmed in the damaged type II pneumocytes and also in the infiltrated macrophages. Real-time RT-PCR analysis of both pre- and post-mortem pharyngeal swabs confirmed a novel influenza (A/H1N1pdm) virus infection. This is the second autopsy case of influenza (A/H1N1pdm) virus infection in Japan, and the findings indicated that the patient died due to an exceptionally rapid progression of viral pneumonia. This case indicates that patients with influenza (A/H1N1pdm) virus infection should be carefully monitor for acute respiratory distress syndrome. PMID:20093769

  2. Immunogenicity and Efficacy of A/H1N1pdm Vaccine Among Subjects With Severe Motor and Intellectual Disability in the 2010/11 Influenza Season

    PubMed Central

    Hara, Megumi; Hanaoka, Tomoyuki; Maeda, Kazuhiro; Kase, Tetsuo; Ohfuji, Satoko; Fukushima, Wakaba; Hirota, Yoshio

    2016-01-01

    Background While the immunogenicity and effectiveness of seasonal influenza vaccines among subjects with severe motor and intellectual disability (SMID) are known to be diminished, the efficacy of the A/H1N1pdm vaccine has not been evaluated. Methods We prospectively evaluated 103 subjects with SMID (mean age, 41.7 years) who received trivalent inactivated influenza vaccine during the 2010/11 influenza season. The hemagglutination inhibition (HI) antibody titer was measured in serum samples collected pre-vaccination (S0), post-vaccination (S1), and end-of-season (S2) to evaluate subjects’ immunogenicity capacity. Vaccine efficacy was assessed based on antibody efficacy and achievement proportion. Results The proportions of seroprotection and seroconversion, and the geometric mean titer (GMT) ratio (GMT at S1/GMT at S0) for A/H1N1pdm were 46.0%, 16.0%, and 1.8, respectively—values which did not meet the European Medicines Evaluation Agency criteria. The achievement proportion was 26%. During follow-up, 11 of 43 subjects with acute respiratory illness were diagnosed with type A influenza according to a rapid influenza diagnostic test (RIDT), and A/H1N1pdm strains were isolated from the throat swabs of 5 of those 11 subjects. When either or both RIDT-diagnosed influenza or serologically diagnosed influenza (HI titer at S2/HI titer at S1 ≥2) were defined as probable influenza, subjects with A/H1N1pdm seroprotection were found to have a lower incidence of probable influenza (odds ratio, 0.31; antibody efficacy, 69%; vaccine efficacy, 18%). Conclusions In the present seasonal assessment, antibody efficacy was moderate against A/H1N1pdm among SMID subjects, but vaccine efficacy was low due to the reduced immunogenicity of SMID subjects. PMID:26780860

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

    SciTech Connect

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

    2010-11-15

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

  4. Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland.

    PubMed

    Bednarska, K; Hallmann-Szelińska, E; Kondratiuk, K; Brydak, L B

    2016-01-01

    Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1-3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes. PMID:26956457

  5. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure of normal human dermal fibroblasts results in AhR-dependent and -independent changes in gene expression

    SciTech Connect

    Akintobi, A.M.; Villano, C.M.; White, L.A. . E-mail: lawhite@aesop.rutgers.edu

    2007-04-01

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a variety of lesions in mammals including severe skin lesions. The majority of TCDD's biological effects are mediated through activation of the aryl hydrocarbon receptor (AhR). We have chosen to examine the effect of TCDD and the AhR pathway on dermal fibroblasts because this cell type plays an integral role in skin homeostasis through the production of cytokines and other factors that regulate epidermal proliferation and differentiation. Our data show that normal human dermal fibroblasts (NHDFs) are responsive to TCDD, as demonstrated by induction of cytochrome p450 1B1 (CYP1B1) expression. Further, our data demonstrate that TCDD treatment of NHDFs results in significant (75-90%) decrease in expression of Id-1 and Id-3, proteins that are involved in regulation of cell proliferation and differentiation. The Id (Inhibitor of DNA binding) proteins are transcriptional inhibitors that function by forming inactive heterodimers with other HLH proteins. TCDD-repression of Id-1 and -3 is independent of de novo protein synthesis; co-treatment with cycloheximide has no effect on TCDD inhibition of Id-1 and Id-3. Co-treatment with the AhR antagonist {alpha}-naphthoflavone also does not block inhibition of Id-1 and Id-3 by TCDD, suggesting that TCDD inhibition of Id-1 and Id-3 is, at least in part, mediated independently of the AhR pathway. Our data also show that TCDD inhibits expression of the cell cycle regulatory gene p16{sup ink4a}, which is often linked to Id expression. TCDD-induced reduction of p16{sup ink4a} expression is also independent of protein synthesis and the AhR pathway.

  6. 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.

  7. Guillain-Barre syndrome, influenzalike illnesses, and influenza vaccination during seasons with and without circulating A/H1N1 viruses.

    PubMed

    Grimaldi-Bensouda, Lamiae; Alpérovitch, Annick; Besson, Gérard; Vial, Christophe; Cuisset, Jean-Marie; Papeix, Caroline; Lyon-Caen, Olivier; Benichou, Jacques; Rossignol, Michel

    2011-08-01

    The role of influenzalike illnesses and influenza vaccination in the development of Guillain-Barré syndrome (GBS), particularly the role of A/H1N1 epidemics and A/H1N1 vaccination, is debated. Data on all incident GBS cases meeting the Brighton Collaboration criteria that were diagnosed at 25 neurology centers in France were prospectively collected between March 2007 and June 2010, covering 3 influenzavirus seasons, including the 2009-2010 A/H1N1 outbreak. A total of 457 general practitioners provided a registry of patients from which 1,080 controls were matched by age, gender, index date (calendar month), and region to 145 cases. Causal relations were assessed by multivariate case-control analysis with adjustment for risk factors (personal and family history of autoimmune disorders, among others), while matching on age, gender, and calendar time. Influenza (seasonal or A/H1N1) or influenzalike symptoms in the 2 months preceding the index date was associated with GBS, with a matched odds ratio of 2.3 (95% confidence interval (CI): 0.7, 8.2). The difference in the rates of GBS occurring between influenza virus circulation periods and noncirculation periods was highly statistically significant (P = 0.004). Adjusted odds ratios for GBS occurrence within 6 weeks after seasonal and A/H1N1 vaccination were 1.3 (95% CI: 0.4, 4.1) and 0.9 (95% CI: 0.1, 7.6), respectively. Study results confirm that influenza virus is a likely risk factor for GBS. Conversely, no new concerns have arisen regarding influenza vaccination.

  8. Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation.

    PubMed

    Liu, Yang; Zhou, Jia-Ying; Zhou, Yu-Hong; Wu, Di; He, Jian-Li; Han, Li-Min; Liang, Xiao-Bo; Wang, Lu-Qi; Lu, Xiao-Long; Chen, Hanying; Qiao, Guo-Fen; Shou, Weinian; Li, Bai-Yan

    2016-04-01

    This study aims to understand the special expression patterns of angiotensin-II receptor (AT1R and AT2R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT1R and AT2R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT2R expression were also tested. The data showed that AT2R, rather than AT1R, expression was higher in female than age-matched male rats. Moreover, AT2R was downregulated in ovariectomized rats, which was restored by the administration of 17β-estradiol. Single-cell real time-polymerase chain reaction data indicated that AT2R was uniquely expressed in Ah-type BRNs. Functional study showed that long-term administration of 17β-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah- than C-type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed by iberiotoxin. The density of angiotensin-II-sensitive K(+) currents recorded in Ah-types was equivalent with iberiotoxin-sensitive component. In summary, the unique, sex- and afferent-specific expression of AT2R was identified in Ah-type BRNs, and AT2R-mediated KCa1.1 inhibition in Ah-type BRNs may exert great impacts on baroreflex afferent function and blood pressure regulation in females. PMID:26883269

  9. 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.

  10. 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

  11. Point of Care Strategy for Rapid Diagnosis of Novel A/H1N1 Influenza Virus

    PubMed Central

    Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Gazin, Celine; Drancourt, Michel; La Scola, Bernard; Raoult, Didier; Charrel, Remi N.

    2010-01-01

    Background Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v), systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC) strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic. Methodology/Principal Findings Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT) and real-time RT-PCR assay (rtRT-PCR). This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours. Conclusions/Significance The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay), because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the

  12. Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

    PubMed Central

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E.; Losso, Marcelo H.; Wentworth, Deborah; Cozzi-Lepri, Alessandro; Herman-Lamin, Kathy; Cholewinska, Grazyna; David, Daniel; Kuetter, Stefan; Ternesgen, Zelalem; Uyeki, Timothy M.; Lane, H. Clifford; Lundgren, Jens; Neaton, James D.

    2014-01-01

    Background Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic

  13. Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

    2016-01-01

    ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of

  14. The Life of Jorjani: One of the Persian Pioneers of Medical Encyclopedia Compiling: On the Occasion of His 1000th Birthday Anniversary (434, A.H. - 1434, A.H.)

    PubMed Central

    Moattar, Fariborz; Shams Ardekani, Mohammad Reza; Ghannadi, Alireza

    2013-01-01

    Background Seyyed Esmaeil Jorjani is one of the most prominent pioneers and scientists of Islamic and Iranian traditional medicine in the 11th and 12th centuries (4th and 5th centuries A.H.). The number of his books is not certainly clear, but it is signified that he has written a couple of great books concerning medicine for Persians and too many treatises in such fields as philosophy, theology, medical ethics, human anatomy, chemistry, pharmacy and other sciences. His most famous and important book is “Zakhireh Khwarazmshahi” or “The Treasure of King Khwarazm”, which is really a complete and valuable medical encyclopedia in Persian language. Materials and Methods In the present study, authors have attempted to state the life and time of Jorjani and his views by studying the history, old medical sources, and other provided recent medical literature in these fields. Results The biography of Hakim Jorjani has been well reviewed and described precisely. Conclusions Based on our findings, it is clear that Jorjani described and explained the symptoms, signs and treatments of several diseases, introduced the activities of various medicinal plants, and compound formulations. He achieved all of this during his continuous visits to prestigious medical centers and famous people of his time. PMID:24616781

  15. Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15.

    PubMed

    Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Rizzo, Caterina; Gherasim, Alin; Horváth, Judit Krisztina; Domegan, Lisa; Pitigoi, Daniela; Machado, Ausenda; Paradowska-Stankiewicz, Iwona Anna; Bella, Antonino; Larrauri, Amparo; Ferenczi, Annamária; Lazar, Mihaela; Pechirra, Pedro; Korczyńska, Monika Roberta; Pozo, Francisco; Moren, Alain

    2016-01-01

    Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and  ≥60  years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and  ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.

  16. General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic

    PubMed Central

    2010-01-01

    Background Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress. Method Between September 1st and 30th, 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28. Results More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008). Conclusions A significant proportion of

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

    PubMed

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

    2015-12-01

    Following the March 2013 outbreak of novel avian influenza A(H7N9) virus in humans and the subsequent isolation of the virus from chickens, ducks and pigeons in the People's Republic of China, concerns were raised that the H7N9 virus would spread beyond China through the poultry value chain linking to a number of bordering countries. For this reason, a rapid emergency surveillance exercise took place in Bhutan between May and July 2013 with the objective of determining whether influenza A(H7N9) virus was silently circulating in domestic poultryandwild birds in Bhutan.Atotal of 1716 oropharyngeal,tracheal and cloacal swabs together with faecal droppings were collected from poultry, wild birds and feral pigeons throughout the country; these samples included 150 that had been previously collected for surveillance of influenza A(H5N1) virus. Overall, 733 of the samples were tested. A QIAamp Viral RNA Mini K it was used to extract viral RNA from a mix of oropharyngeal, tracheal and cloacal swabs and faecal droppings. The matrix gene of avian influenza type A virus was detected using a specific real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay, and positive samples were further tested in RT-PCR for simultaneous detection of the H7 and N9 genes. Among the 733 samples tested, 46 (26 prospective, 20 retrospective) were confirmed positive for influenza A, a prevalence of 6.3% (95% CI: 4.6 to 8.3). The influenza A-positive samples were from areas in the south of Bhutan that had experienced previous outbreaks of highly pathogenic influenza A(H5N1). None of the samples tested positive for H7N9 strains, providing evidence that influenza A(H7N9) virus was not present in the sampled population. A risk-based approach for surveillance of influenza A(H7N9) and H5N1 is recommended in Bhutan, based on the epidemiology of the disease in China and other countries in South and Southeast Asia. PMID:27044154

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

    PubMed

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

    2015-12-01

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

  19. Elucidation of the Vibrio anguillarum Genetic Response to the Potential Fish Probiont Pseudomonas fluorescens AH2, Using RNA-Arbitrarily Primed PCR

    PubMed Central

    Holmstrøm, Kim; Gram, Lone

    2003-01-01

    The antagonistic interaction between a potential fish probiont, Pseudomonas fluorescens strain AH2, and its target organism, Vibrio anguillarum, was investigated by studying the genetic response of the target organism when it was exposed to the antagonist. We compared the differential display of arbitrarily PCR-amplified gene transcripts in V. anguillarum serotype O1 when it was exposed to AH2 supernatant with the display of transcripts in nonexposed control cultures. Growth of V. anguillarum was immediately arrested when the organism was exposed to 50% (vol/vol) AH2 supernatant. A total of 10 potentially differentially expressed transcripts were identified. Among these we identified a gene homologous to rpoS that was induced in a dose-dependent manner when V. anguillarum was cultured in media supplemented with sterile filtered supernatant from AH2. rpoS was also induced when growth was arrested with the iron chelator 2,2-dipyridyl. A chromosomal transcript homologous to vibE that participates in vibriobactin synthesis in Vibrio cholerae was also upregulated during AH2 exposure. This transcript could represent a functionally active gene in V. anguillarum involved in biosynthesis of anguibactin or another V. anguillarum siderophore. On the pJM1 plasmid of V. anguillarum serotype O1, a pseudogene designated open reading frame E (ORF E) that contains a frameshift mutation was previously identified. The gene homologous to vibE identified in this study, interestingly, also has significant homology to ORF E on the amino acid level and does not possess the frameshift mutation. Thus, the chromosomally encoded vibE homologue could fulfil the role of the inactive plasmid-encoded ORF E pseudogene. Addition of Fe3+ to the system eliminated the growth arrest, and the genes homologous to rpoS and vibE were not induced. To our knowledge, this is the first study linking rpoS induction to iron starvation. Taken together, the results of this study suggest that a major part of the

  20. Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk

    PubMed Central

    Skowronski, Danuta M.; Hamelin, Marie-Eve; De Serres, Gaston; Janjua, Naveed Z.; Li, Guiyun; Sabaiduc, Suzana; Bouhy, Xavier; Couture, Christian; Leung, Anders; Kobasa, Darwyn; Embury-Hyatt, Carissa; de Bruin, Erwin; Balshaw, Robert; Lavigne, Sophie; Petric, Martin; Koopmans, Marion; Boivin, Guy

    2014-01-01

    During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in

  1. The very energetic, broad-lined Type Ic supernova 2010ah (PTF10bzf) in the context of GRB/SNe

    NASA Astrophysics Data System (ADS)

    Mazzali, Paolo A.; Walker, Emma S.; Pian, Elena; Tanaka, Masaomi; Corsi, Alessandra; Hattori, Takashi; Gal-Yam, Avishay

    2013-07-01

    SN 2010ah, a very broad-lined Type Ic supernova (SN) discovered by the Palomar Transient Factory, was interesting because of its relatively high luminosity and the high velocity of the absorption lines, which was comparable to that of gamma-ray burst (GRB)/SNe, suggesting a high explosion kinetic energy. However, no GRB was detected in association with the SN. Here, the properties of SN 2010ah are determined with higher accuracy than previous studies through modelling. New Subaru telescope photometry is presented. A bolometric light curve is constructed taking advantage of the spectral similarity with SN 1998bw. Radiation transport tools are used to reproduce the spectra and the light curve. The results thus obtained regarding ejecta mass, composition and kinetic energy are then used to compute a synthetic light curve. This is in reasonable agreement with the early bolometric light curve of SN 2010ah, but a high abundance of 56Ni at high velocity is required to reproduce the early rise, while a dense inner core must be used to reproduce the slow decline at late phases. The high-velocity 56Ni cannot have been located on our line of sight, which may be indirect evidence for an off-axis, aspherical explosion. The main properties of SN 2010ah are: ejected mass Mej ≈ 3 M⊙; kinetic energy Ekin ≈ 1052 erg, M(56Ni) ≈ 0.25 M⊙. The mass located at v ≳ 0.1 c is ˜0.2 M⊙. Although these values, in particular the Ekin, are quite large for a Type Ic SN, they are all smaller (especially Mej) than those typical of GRB/SNe. This confirms the tendency for these quantities to correlate, and suggests that there are minimum requirements for a GRB/SN, which SN 2010ah may not meet although it comes quite close. Depending on whether a neutron star or a black hole was formed following core collapse, SN 2010ah was the explosion of a CO core of ˜5 to 6 M⊙, pointing to a progenitor mass of ˜24-28 M⊙.

  2. Effects of Developmental Activation of the AhR on CD4+ T-Cell Responses to Influenza Virus Infection in Adult Mice

    PubMed Central

    Boule, Lisbeth A.; Winans, Bethany

    2014-01-01

    Background: Epidemiological and animal studies indicate that maternal exposure to pollutants that bind the aryl hydrocarbon receptor (AhR) correlates with poorer ability to combat respiratory infection and lower antibody levels in the offspring. These observations point to an impact on CD4+ T cells. Yet, the consequence of developmental exposure to AhR ligands on the activation and differentiation of CD4+ T cells has not been directly examined. Objectives: Our goal was to determine whether maternal exposure to an AhR ligand directly alters CD4+ T cell differentiation and function later in life. Methods: C57BL/6 mice were exposed to a prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in utero and via suckling. We then measured CD4+ T-cell activation and differentiation into distinct effector populations in adult offspring that were infected with influenza A virus (IAV). Reciprocal adoptive transfers were used to define whether modifications in CD4+ T-cell responses resulted from direct effects of developmental TCDD exposure on CD4+ T cells. Results: Developmental exposure skewed CD4+ T-cell responses to IAV infection. We observed fewer virus-specific, activated CD4+ T cells and a reduced frequency of conventional CD4+ effector-cell subsets. However, there was an increase in regulatory CD4+ T cells. Direct effects of AhR activation on CD4+ T cells resulted in impaired differentiation into conventional effector subsets; this defect was transferred to mice that had not been developmentally exposed to TCDD. Conclusions: Maternal exposure to TCDD resulted in durable changes in the responsive capacity and differentiation of CD4+ T cells in adult C57BL/6 mice. Citation: Boule LA, Winans B, Lawrence BP. 2014. Effects of developmental activation of the AhR on CD4+ T-cell responses to influenza virus infection in adult mice. Environ Health Perspect 122:1201–1208; http://dx.doi.org/10.1289/ehp.1408110 PMID:25051576

  3. Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis

    PubMed Central

    Wong, Jessica Y.; Kelly, Heath; Cheung, Chung-Mei M.; Shiu, Eunice Y.; Wu, Peng; Ni, Michael Y.; Ip, Dennis K. M.; Cowling, Benjamin J.

    2015-01-01

    During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%–3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting. PMID:26188191

  4. Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase.

    PubMed

    Ramírez-Salinas, Gema L; García-Machorro, J; Quiliano, Miguel; Zimic, Mirko; Briz, Verónica; Rojas-Hernández, Saul; Correa-Basurto, J

    2015-11-01

    The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50 ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir.

  5. Modelling the spatial-temporal progression of the 2009 A/H1N1 influenza pandemic in Chile.

    PubMed

    Bürger, Raimund; Chowell, Gerardo; Mulet, Pep; Villada, Luis M

    2016-02-01

    A spatial-temporal transmission model of 2009 A/H1N1 pandemic influenza across Chile, a country that spans a large latitudinal range, is developed to characterize the spatial variation in peak timing of that pandemic as a function of local transmission rates, spatial connectivity assumptions for Chilean regions, and the putative location of introduction of the novel virus into the country. Specifically, a metapopulation SEIR (susceptible-exposed-infected-removed) compartmental model that tracks the transmission dynamics of influenza in 15 Chilean regions is calibrated. The model incorporates population mobility among neighboring regions and indirect mobility to and from other regions via the metropolitan central region ('hub region'). The stability of the disease-free equilibrium of this model is analyzed and compared with the corresponding stability in each region, concluding that stability may occur even with some regions having basic reproduction numbers above 1. The transmission model is used along with epidemiological data to explore potential factors that could have driven the spatial-temporal progression of the pandemic. Simulations and sensitivity analyses indicate that this relatively simple model is sufficient to characterize the south-north gradient in peak timing observed during the pandemic, and suggest that south Chile observed the initial spread of the pandemic virus, which is in line with a retrospective epidemiological study. The 'hub region' in our model significantly enhanced population mixing in a short time scale.

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

    PubMed

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

    2015-01-01

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

  7. Gene signatures related to HAI response following influenza A/H1N1 vaccine in older individuals.

    PubMed

    Ovsyannikova, Inna G; Oberg, Ann L; Kennedy, Richard B; Zimmermann, Michael T; Haralambieva, Iana H; Goergen, Krista M; Grill, Diane E; Poland, Gregory A

    2016-05-01

    To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination. We identified a number of uncharacterized genes (ZNF300, NUP1333, KLK1 and others) and confirmed previous studies demonstrating specific genes/genesets that are important mediators of host immune responses and that displayed associations with antibody response to influenza A/H1N1 vaccine. These included interferon-regulatory transcription factors (IRF1/IRF2/IRF6/IRF7/IRF9), chemokine/chemokine receptors (CCR5/CCR9/CCL5), cytokine/cytokine receptors (IFNG/IL10RA/TNFRSF1A), protein kinases (MAP2K4/MAPK3), growth factor receptor (TGFBR1). The identification of gene signatures associated with antibody response represents an early stage in the science for which further research is needed. Such research may assist in the design of better vaccines to facilitate improved defenses against new influenza virus strains, as well as better understanding the genetic drivers of immune responses. PMID:27441275

  8. In vitro antiviral activity of hypothiocyanite against A/H1N1/2009 pandemic influenza virus.

    PubMed

    Cegolon, L; Salata, C; Piccoli, E; Juarez, V; Palu', G; Mastrangelo, G; Calistri, A

    2014-01-01

    Influenza virus spreads via small particle aerosols, droplets and fomites, and since it can survive for a short time on surfaces, can be introduced into the nasal mucosa before it loses infectivity. The hypothiocyanite ion (OSCN-), product of the lactoperoxidase/H2O2/SCN- system of central airways, is emerging as an important molecule for innate defense mechanism against bacteria, fungi and viruses. Here we demonstrated that OSCN(-) displays virucidal activity in vitro against the A/H1N1 2009 pandemic influenza virus. The concentration required to inhibit viral replication by 50% was 2 μM when virus were challenged directly with OSCN- before cell inoculation. These values were even lower when inoculated cells were maintained in contact with enzyme free-OSCN- in the culture medium. The last experimental conditions better reflect those of tracheobronchial mucosa, where HOSCN/OSCN- is retained in the air-liquid interface and inactivates both the viruses approaching the epithelium from outside and those released from the inoculated cells after the replication cycle. Importantly no OSCN- cytotoxicity was observed in the cellular system employed. The lack of toxicity in humans and the absence of damage on surfaces of fomites suggest a potential use of OSCN- to avoid mucosal and environmental transmission of influenza virus. Since hypothiocyanite is normally present in human airways a low risk of viral resistance is envisaged. In vivo confirmatory studies are needed to evaluate the appropriate dose, regimen and formulation.

  9. Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Freidl, Gudrun S.; van den Ham, Henk-Jan; Boni, Maciej F.; de Bruin, Erwin; Koopmans, Marion P.G.

    2016-01-01

    Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses. PMID:26853924

  10. Molecular modeling studies demonstrate key mutations that could affect the ligand recognition by influenza AH1N1 neuraminidase.

    PubMed

    Ramírez-Salinas, Gema L; García-Machorro, J; Quiliano, Miguel; Zimic, Mirko; Briz, Verónica; Rojas-Hernández, Saul; Correa-Basurto, J

    2015-11-01

    The goal of this study was to identify neuraminidase (NA) residue mutants from human influenza AH1N1 using sequences from 1918 to 2012. Multiple alignment studies of complete NA sequences (5732) were performed. Subsequently, the crystallographic structure of the 1918 influenza (PDB ID: 3BEQ-A) was used as a wild-type structure and three-dimensional (3-D) template for homology modeling of the mutated selected NA sequences. The 3-D mutated NAs were refined using molecular dynamics (MD) simulations (50 ns). The refined 3-D models were used to perform docking studies using oseltamivir. Multiple sequence alignment studies showed seven representative mutations (A232V, K262R, V263I, T264V, S367L, S369N, and S369K). MD simulations applied to 3-D NAs showed that each NA had different active-site shapes according to structural surface visualization and docking results. Moreover, Cartesian principal component analyses (cPCA) show structural differences among these NA structures caused by mutations. These theoretical results suggest that the selected mutations that are located outside of the active site of NA could affect oseltamivir recognition and could be associated with resistance to oseltamivir. PMID:26499499

  11. Beliefs and knowledge about vaccination against AH1N1pdm09 infection and uptake factors among Chinese parents.

    PubMed

    Wu, Cynthia Sau Ting; Kwong, Enid Wai Yung; Wong, Ho Ting; Lo, Suet Hang; Wong, Anthony Siu Wo

    2014-02-01

    Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R2 of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.

  12. Efficient production of laccases by Trametes sp. AH28-2 in cocultivation with a Trichoderma strain.

    PubMed

    Zhang, H; Hong, Y Z; Xiao, Y Z; Yuan, J; Tu, X M; Zhang, X Q

    2006-11-01

    A biocontrol fungus isolated from rotting wood was identified as a Trichoderma strain (named as Trichoderma sp. ZH1) by internal transcribed spacer (ITS) sequences of rRNA genes. The laccase yield of Trametes sp. AH28-2 in cocultivation with Trichoderma sp. ZH1 reached 6,210 U l(-1), approximately identical to those induced by toxic aromatic inducers. Cocultures maintained 60-70 % of their highest laccase activity obtained at 5 days after inoculation of the biocontrol fungus, at least for 20 days. Furthermore, a novel laccase isozyme (LacC) was obtained through the fungal interactions. The molecular weight of LacC is about 64 kDa, and its isoelectric point is 6.6. The temperature and pH optimum for LacC to oxidize guaiacol are 55 degrees C and 5.0, respectively. LacC is stable both at 60 degrees C and pH 4.0-8.0. Furthermore, the K (m) values of LacC for various substrates were also determined. Our work demonstrates a safe strategy for the production of industrial laccases, instead of the traditional method of chemical induction.

  13. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus

    PubMed Central

    Linster, Martin; van Boheemen, Sander; de Graaf, Miranda; Schrauwen, Eefje J. A.; Lexmond, Pascal; Mänz, Benjamin; Bestebroer, Theo M.; Baumann, Jan; van Riel, Debby; Rimmelzwaan, Guus F.; Osterhaus, Albert D.M.E.; Matrosovich, Mikhail; Fouchier, Ron A. M.; Herfst, Sander

    2014-01-01

    SUMMARY Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments. PMID:24725402

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

    PubMed Central

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

    2015-01-01

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

  15. Hot gas ingestion effects on fuel control surge recovery and AH-1 rotor drive train torque spikes

    NASA Technical Reports Server (NTRS)

    Tokarski, Frank; Desai, Mihir; Books, Martin; Zagranski, Raymond

    1994-01-01

    This report summarizes the work accomplished through computer simulation to understand the impact of the hydromechanical turbine assembly (TA) fuel control on rocket gas ingestion induced engine surges on the AH-1 (Cobra) helicopter. These surges excite the lightly damped torsional modes of the Cobra rotor drive train and can cause overtorqueing of the tail rotor shaft. The simulation studies show that the hydromechanical TA control has a negligible effect on drive train resonances because its response is sufficiently attenuated at the resonant frequencies. However, a digital electronic control working through the TA control's separate, emergency fuel metering system has been identified as a solution to the overtorqueing problem. State-of-the-art software within the electronic control can provide active damping of the rotor drive train to eliminate excessive torque spikes due to any disturbances including engine surges and aggressive helicopter maneuvers. Modifications to the existing TA hydromechanical control are relatively minor, and existing engine sensors can be utilized by the electronic control. Therefore, it is concluded that the combination of full authority digital electronic control (FADEC) with hydromechanical backup using the existing TA control enhances flight safety, improves helicopter performance, reduces pilot workload, and provides a substantial payback for very little investment.

  16. The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability

    PubMed Central

    Castelán-Vega, Juan A; Magaña-Hernández, Anastasia; Jiménez-Alberto, Alicia; Ribas-Aparicio, Rosa María

    2014-01-01

    The last influenza A pandemic provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates since the beginning of the pandemic until date, we could monitor amino acid changes that occurred in the hemagglutinin (HA) as the virus spread worldwide and became the dominant H1N1 strain. HA is crucial to viral infection because it binds to sialidated cell-receptors and mediates fusion of cell and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. Multiple alignment analysis of sequences of the HA from isolates taken since 2009 to date allowed us to find amino acid changes that were positively selected as the pandemic progressed. We found nine changes that became prevalent: HA1 subunits D104N, K166Q, S188T, S206T, A259T, and K285E; and HA2 subunits E47K, S124N, and E172K. Most of these changes were located in areas involved in inter- and intrachain interactions, while only two (K166Q and S188T) were located in known antigenic sites. We conclude that selective pressure on HA was aimed to improve its functionality and hence virus fitness, rather than at avoidance of immune recognition. PMID:25328411

  17. Modelling the spatial-temporal progression of the 2009 A/H1N1 influenza pandemic in Chile.

    PubMed

    Bürger, Raimund; Chowell, Gerardo; Mulet, Pep; Villada, Luis M

    2016-02-01

    A spatial-temporal transmission model of 2009 A/H1N1 pandemic influenza across Chile, a country that spans a large latitudinal range, is developed to characterize the spatial variation in peak timing of that pandemic as a function of local transmission rates, spatial connectivity assumptions for Chilean regions, and the putative location of introduction of the novel virus into the country. Specifically, a metapopulation SEIR (susceptible-exposed-infected-removed) compartmental model that tracks the transmission dynamics of influenza in 15 Chilean regions is calibrated. The model incorporates population mobility among neighboring regions and indirect mobility to and from other regions via the metropolitan central region ('hub region'). The stability of the disease-free equilibrium of this model is analyzed and compared with the corresponding stability in each region, concluding that stability may occur even with some regions having basic reproduction numbers above 1. The transmission model is used along with epidemiological data to explore potential factors that could have driven the spatial-temporal progression of the pandemic. Simulations and sensitivity analyses indicate that this relatively simple model is sufficient to characterize the south-north gradient in peak timing observed during the pandemic, and suggest that south Chile observed the initial spread of the pandemic virus, which is in line with a retrospective epidemiological study. The 'hub region' in our model significantly enhanced population mixing in a short time scale. PMID:26776260

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

    PubMed

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

    2015-01-01

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

  19. Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks

    PubMed Central

    2013-01-01

    Background As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. Methods Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. Results The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. Conclusions These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities. PMID:24359669

  20. Precursors to potential severe core damage accidents: 1994, a status report. Volume 21: Main report and appendices A--H

    SciTech Connect

    Belles, R.J.; Cletcher, J.W.; Copinger, D.A.; Vanden Heuvel, L.N.; Dolan, B.W.; Minarick, J.W. |

    1995-12-01

    Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1.

  1. Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

    PubMed Central

    2012-01-01

    Background Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics. In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico. Methods We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system

  2. Neutron scattering studies of the H2a-H2b and (H3-H4)/sub 2/ histone complexes

    SciTech Connect

    Carlson, R.D.

    1982-01-01

    Neutron scattering experiments have shown that both the (H3-H4)/sub 2/ and H2a-H2b histone complexes are quite asymmetric in solution. The (H3-H4)/sub 2/ tetramer is an oblate or flattened structure, with a radius of gyration almost as large as that of the core octamer. If the tetramer is primarily globular, it must have an axial ratio of about 1:5. It is more likely, however, that this asymmetry results in part from N-terminal arms that extend outward approximately within the major plane of the particle. If this is the case, less asymmetric models for the globular part of the tetramer, including a dislocated disk, can be made consistent with the scattering data. The H2a-H2b dimer, on the other hand, is an elongated structure. 48 references, 12 figures, 1 table.

  3. Aerodynamic Performance of a 0.27-Scale Model of an AH-64 Helicopter with Baseline and Alternate Rotor Blade Sets

    NASA Technical Reports Server (NTRS)

    Kelley, Henry L.

    1990-01-01

    Performance of a 27 percent scale model rotor designed for the AH-64 helicopter (alternate rotor) was measured in hover and forward flight and compared against and AH-64 baseline rotor model. Thrust, rotor tip Mach number, advance ratio, and ground proximity were varied. In hover, at a nominal thrust coefficient of 0.0064, the power savings was about 6.4 percent for the alternate rotor compared to the baseline. The corresponding thrust increase at this condition was approx. 4.5 percent which represents an equivalent full scale increase in lift capability of about 660 lbs. Comparable results were noted in forward flight except for the high thrust, high speed cases investigated where the baseline rotor was slightly superior. Reduced performance at the higher thrusts and speeds was likely due to Reynolds number effects and blade elasticity differences.

  4. Structure Change from β-Strand and Turn to α-Helix in Histone H2A-H2B Induced by DNA Damage Response.

    PubMed

    Izumi, Yudai; Fujii, Kentaro; Wien, Frank; Houée-Lévin, Chantal; Lacombe, Sandrine; Salado-Leza, Daniela; Porcel, Erika; Masoud, Rawand; Yamamoto, Satoshi; Réfrégiers, Matthieu; Hervé du Penhoat, Marie-Anne; Yokoya, Akinari

    2016-07-12

    Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of α-helix structure and a decrease of β-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new α-helix structures at 310 K. We propose the structural transition from β-strand and turn structures to an α-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response.

  5. Using multiple linear regression and physicochemical changes of amino acid mutations to predict antigenic variants of influenza A/H3N2 viruses.

    PubMed

    Cui, Haibo; Wei, Xiaomei; Huang, Yu; Hu, Bin; Fang, Yaping; Wang, Jia

    2014-01-01

    Among human influenza viruses, strain A/H3N2 accounts for over a quarter of a million deaths annually. Antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. In this study, a computational model was developed to predict antigenic variants of the A/H3N2 strain. First, 18 critical antigenic amino acids in the hemagglutinin (HA) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. Next, a prediction model was developed by integrating multiple linear regression method with eight types of physicochemical changes in critical amino acid positions. When compared to other three known models, our prediction model achieved the best performance not only on the training dataset but also on the commonly-used testing dataset composed of 31878 antigenic relationships of the H3N2 influenza virus.

  6. Biological characteristics of influenza A(H1N1)pdm09 virus circulating in West Siberia during pandemic and post-pandemic periods.

    PubMed

    Prokop'eva, E A; Kurskaya, O G; Saifutdinova, S G; Glushchenko, A V; Shestopalova, L V; Shestopalov, A M; Shkurupii, V A

    2014-03-01

    We studied biological characteristics of influenza A(H1N1)pdm09 virus circulating in Siberia during the 2009 pandemic and the post-pandemic period of 2011. BALB/c mice were chosen as the experimental model. Virus titers in the lungs were evaluated on days 1, 3, 6 and blood serum titers on day 15 after infection with different strains. Blood sera of convalescents after influenza of 2010-2011 epidemic season were analyzed. Influenza A(H1N1)pdm09 virus strains isolated during the post-pandemic period of 2011 were characterized by low epidemic activity and virulence in comparison with the strains isolated during 2009 pandemic period, which indicates completion of the pandemic cycle.

  7. 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.

  8. Relation among cytochrome P450, Ah-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

    SciTech Connect

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W. . Patuxent Environmental Science Center); Tillitt, D.E. . Midwest Science Center)

    1994-11-01

    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 P450-associated mono-oxygenates and cytochrome P450 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[sup 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.

  9. 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 P450-associated monooxygenases and cytochrome P450 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 super(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.

  10. 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.

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

    PubMed Central

    Jaguin, Marie; Fardel, Olivier; Lecureur, Valérie

    2015-01-01

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

  12. Selective Aryl Hydrocarbon Receptor Modulator 3,3'-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia.

    PubMed

    Rzemieniec, J; Litwa, E; Wnuk, A; Lason, W; Krzeptowski, W; Kajta, M

    2016-10-01

    The neuroprotective potential of 3,3'-diindolylmethane (DIM), which is a selective aryl hydrocarbon receptor modulator, has recently been shown in cellular and animal models of Parkinson's disease and lipopolysaccharide-induced inflammation. However, there are no data concerning the protective capacity and mechanisms of DIM action in neuronal cells exposed to hypoxia. The aim of the present study was to investigate the neuroprotective potential of DIM against the hypoxia-induced damage in mouse hippocampal cells in primary cultures, with a particular focus on DIM interactions with the aryl hydrocarbon receptor (AhR), its nuclear translocator ARNT, and estrogen receptor β (ERβ). In the present study, 18 h of hypoxia induced apoptotic processes, in terms of the mitochondrial membrane potential, activation of caspase-3, and fragmentation of cell nuclei. These effects were accompanied by substantial lactate dehydrogenase release and neuronal cell death. The results of the present study demonstrated strong neuroprotective and anti-apoptotic actions of DIM in hippocampal cells exposed to hypoxia. In addition, DIM decreased the Ahr and Arnt mRNA expression and stimulated Erβ mRNA expression level. DIM-induced mRNA alterations were mirrored by changes in protein levels, except for ERβ, as detected by ELISA, Western blotting, and immunofluorescence labeling. We also demonstrated that DIM decreased the expression of AhR-regulated CYP1A1. Using specific siRNAs, we provided evidence that impairment of AhR and ARNT, but not ERβ plays a key role in the neuroprotective action of DIM against hypoxia-induced cell damage. This study may have implication for identifying new agents that could protect neurons against hypoxia by targeting AhR/ARNT signaling. PMID:26476840

  13. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran

    PubMed Central

    Sharifirad, Gholamreza; Yarmohammadi, Parastoo; Sharifabad, Mohammad Ali Morowati; Rahaei, Zohreh

    2014-01-01

    Introduction: Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students’ preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT). Materials and Methods: In a cross-sectional study, multiple-stage randomized sampling was used to select 300 female students in Isfahan who completed a questionnaire in December 2009. Data were collected using a self-report questionnaire based on PMT. The statistical analysis of the data included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear regression. Results: The mean age of participants was 15.62 (SE = 1.1) years old. Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%, 262 out of 300). Results showed that, protection motivation was highly significant relationship with preventive behavior and predicted 34% of its variance. We found all of the variables with the exception of perceived susceptibility, perceived severity, and response cost were related with protection motivation and explained 22% of its variance. Conclusion: Promotion of students’ self-efficacy, and intention to protect themselves from a health threat should be priorities of any programs aimed at promoting preventive behaviors among students. It is also concluded that the protection motivation theory may be used in developing countries, like Iran, as a framework for prevention interventions in an attempt to improve the preventive behaviors of students. PMID:24741647

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

    PubMed

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

    2016-06-01

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

  15. Mortality Burden of the A/H1N1 Pandemic in Mexico: A Comparison of Deaths and Years of Life Lost to Seasonal Influenza

    PubMed Central

    Charu, Vivek; Chowell, Gerardo; Palacio Mejia, Lina Sofia; Echevarría-Zuno, Santiago; Borja-Aburto, Víctor H.; Simonsen, Lone; Miller, Mark A.

    2011-01-01

    Background. The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. Methods. Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory-confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. Results. The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100 000 population and 445 000 YLL during the 3 waves of virus activity in Mexico, April–December 2009. The pandemic mortality burden was 0.6–2.6 times that of a typical influenza season and lower than that of the severe 2003–2004 influenza epidemic. Individuals aged 5–19 and 20–59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. Conclusions. Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic. PMID:21976464

  16. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  17. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  18. Two years after the Hebei Spirit oil spill: residual crude-derived hydrocarbons and potential AhR-mediated activities in coastal sediments.

    PubMed

    Hong, Seongjin; Khim, Jong Seong; Ryu, Jongseong; Park, Jinsoon; Song, Sung Joon; Kwon, Bong-Oh; Choi, Kyungho; Ji, Kyunghee; Seo, Jihyun; Lee, Sangwoo; Park, Jeongim; Lee, Woojin; Choi, Yeyong; Lee, Kyu Tae; Kim, Chan-Kook; Shim, Won Joon; Naile, Jonathan E; Giesy, John P

    2012-02-01

    The Hebei Spirit oil spill occurred in December 2007 approximately 10 km off the coast of Taean, South Korea, on the Yellow Sea. However, the exposure and potential effects remain largely unknown. A total of 50 surface and subsurface sediment samples were collected from 22 sampling locations at the spill site in order to determine the concentration, distribution, composition of residual crudes, and to evaluate the potential ecological risk after two years of oil exposure. Samples were extracted and analyzed for 16 polycyclic aromatic hydrocarbons (PAHs), 20 alkyl-PAHs, 15 aliphatic hydrocarbons, and total petroleum hydrocarbons using GC-MSD. AhR-mediated activity associated with organic sediment extracts was screened using the H4IIE-luc cell bioassay. The response of the benthic invertebrate community was assessed by mapping the macrobenthic fauna. Elevated concentrations of residual crudes from the oil spill were primarily found in muddy bottoms, particularly in subsurface layers. In general, the bioassay results were consistent with the chemistry data in a dose-dependent manner, although the mass-balance was incomplete. More weathered samples containing greater fractions of alkylated PAHs exhibited greater AhR activity, due to the occurrence of recalcitrant AhR agonists present in residual oils. The macrobenthic population distribution exhibits signs of species-specific tolerances and/or recolonization of certain species such as Batillaria during weathering periods. Although the Hebei Spirit oil spill was a severe oil exposure, it appears the site is recovering two years later.

  19. Serum antibody response to matrix protein 2 following natural infection with 2009 pandemic influenza A(H1N1) virus in humans.

    PubMed

    Zhong, Weimin; Reed, Carrie; Blair, Patrick J; Katz, Jacqueline M; Hancock, Kathy

    2014-04-01

    Natural infection-induced humoral immunity to matrix protein 2 (M2) of influenza A viruses in humans is not fully understood. Evidence suggests that anti-M2 antibody responses following influenza A virus infection are weak and/or transient. We show that the seroprevalence of anti-M2 antibodies increased with age in 317 serum samples from healthy individuals in the United States in 2007-2008. Infection with 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) elicited a recall serum antibody response to M2 protein of A(H1N1)pdm09 in 47% of the affected 118 individuals tested. Anti-M2 antibody responses were more robust among individuals with preexisting antibodies to M2 protein. Moreover, the antibodies induced as a result of infection with A(H1N1)pdm09 were cross-reactive with M2 protein of seasonal influenza A viruses. These results emphasize the need to further investigate the possible roles of anti-M2 antibodies in human influenza A virus infection. PMID:24325965

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

    PubMed

    Remiche, Gauthier; Abramowicz, Marc; Mavroudakis, Nicolas

    2013-12-01

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

  1. Effects of a nutrient mixture on infectious properties of the highly pathogenic strain of avian influenza virus A/H5N1.

    PubMed

    Deryabin, Petr G; Lvov, Dmitry K; Botikov, Andrey G; Ivanov, Vadim; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2008-01-01

    Numerous outbreaks of avian influenza virus infection (A/H5N1) have occurred recently, infecting domestic birds, chicken and ducks. The possibility of the emergence of a new strain of influenza virus capable of causing a pandemic in humans is high and no vaccine effective against such a strain currently exists. A unique nutrient mixture (NM), containing lysine, proline, ascorbic acid, green tea extract, N-acetyl cysteine, selenium among other micro nutrients, has been shown to exert a wide range of biochemical and pharmacological effects, including an inhibitory effect on replication of influenza virus and HIV. This prompted us to investigate the potential anti-viral activity of a nutrient mixture (NM) and its components on avian influenza virus A/H5N1at viral dosages of 1.0, 0.1 and 0.01 TCID(50). Antiviral activity was studied in cultured cell lines PK, BHK-21, and Vero-E6. Virus lysing activity was determined by co-incubation of virus A/H5N1 with NM for 0-60 min, followed residual virulence titration in cultured SPEV or BHK-21 cells. NM demonstrated high antiviral activity evident even at prolonged periods after infection. NM antiviral properties were comparable to those of conventional drugs (amantadine and oseltamivir); however, NM had the advantage of affecting viral replication at the late stages of the infection process.

  2. 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

  3. Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age.

    PubMed

    Fielding, James E; Kelly, Heath A; Mercer, Geoffry N; Glass, Kathryn

    2014-03-01

    Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

  4. Why were Turks unwilling to accept the A/H1N1 influenza-pandemic vaccination? People's beliefs and perceptions about the swine flu outbreak and vaccine in the later stage of the epidemic.

    PubMed

    Gaygısız, Ümmügülsüm; Gaygısız, Esma; Özkan, Türker; Lajunen, Timo

    2010-12-16

    This study investigated the acceptability of the A/H1N1 influenza vaccination and related factors among 1137 adults in the later stage of the A/H1N1 outbreak in Turkey. Having already been vaccinated or intending to get vaccinated were related to trust in the vaccine effectiveness, perceived risk of the side effects, and benefits of getting vaccinated. Perceived long term consequences of the A/H1N1 infection, perceptions of the A/H1N1 information in media, and barriers for getting vaccinated were related to intention whereas anticipated epidemic situation in Turkey, being chronically ill, and being not married were related to having already been vaccinated.

  5. Impact of prior seasonal H3N2 influenza vaccination or infection on protection and transmission of emerging variants of influenza A(H3N2)v virus in ferrets.

    PubMed

    Houser, Katherine V; Pearce, Melissa B; Katz, Jacqueline M; Tumpey, Terrence M

    2013-12-01

    Influenza H3N2 A viruses continue to circulate in swine and occasionally infect humans, resulting in outbreaks of variant influenza H3N2 [A(H3N2)v] virus. It has been previously demonstrated in ferrets that A(H3N2)v viruses transmit as efficiently as seasonal influenza viruses, raising concern over the pandemic potential of these viruses. However, A(H3N2)v viruses have not acquired the ability to transmit efficiently among humans, which may be due in part to existing cross-reactive immunity to A(H3N2)v viruses. Although current seasonal H3N2 and A(H3N2)v viruses are antigenically distinct from one another, historical H3N2 viruses have some antigenic similarity to A(H3N2)v viruses and previous exposure to these viruses may provide a measure of immune protection sufficient to dampen A(H3N2)v virus transmission. Here, we evaluated whether prior seasonal H3N2 influenza virus vaccination or infection affects virus replication and transmission of A(H3N2)v virus in the ferret animal model. We found that the seasonal trivalent inactivated influenza virus vaccine (TIV) or a monovalent vaccine prepared from an antigenically related 1992 seasonal influenza H3N2 (A/Beijing/32/1992) virus failed to substantially reduce A(H3N2)v (A/Indiana/08/2011) virus shedding and subsequent transmission to naive hosts. Conversely, ferrets primed by seasonal H3N2 virus infection displayed reduced A(H3N2)v virus shedding following challenge, which blunted transmission to naive ferrets. A higher level of specific IgG and IgA antibody titers detected among infected versus vaccinated ferrets was associated with the degree of protection offered by seasonal H3N2 virus infection. The data demonstrate in ferrets that the efficiency of A(H3N2)v transmission is disrupted by preexisting immunity induced by seasonal H3N2 virus infection.

  6. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination

    PubMed Central

    Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31–50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  7. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    PubMed

    Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina

    2015-05-01

    Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during