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Sample records for ah ah ah

  1. "Jum'ah" syndrome.

    PubMed

    Kannai, Ruth

    2012-05-01

    This is my memoir as a sick child, hospitalized in the Pediatric ward of a large hospital, many years ago. The story tells about my friendship with another young patient, Jum'ah, a Bedouin child who suffered from Congenital Cyanotic Heart Disease, to whom the pediatric ward was Home. My Childish understanding of Jum'ah's loneliness, anxiety and struggle to be loved and belonged are described in this narrative. I describe how this experience still has an influence on my adult professional and personal concepts. PMID:21943791

  2. 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.

  3. CHARACTERIZATION OF THE AH RECEPTOR

    EPA Science Inventory

    The rat liver cytosolic receptor protein containing the Ah-receptor protein was purified and studied using a photochemical assembly of 2,3,7,8-TCDD. The unbound receptor protein rapidly lost its capacity to bind 2,3,7,8-TCDD; however, the 2,3,7,8-TCDD bound Ah receptor did not re...

  4. 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.

  5. 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...

  6. CCD Campaign to Observe AH Leonis

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2006-04-01

    Dr. Pamela Gay, Harvard University, has requested optical observations of the RR Lyrae variable star AH Leonis in order to study the Blazhko cycle and other periodicities in this star. Coordinates, finding chart/sequence, observing instructions, and link to AAVSO Variable Star of the Season article on AH Leo (http://www.aavso.org/vstar/vsots/) are provided.

  7. 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

  8. In-flight AHS MTF measurements

    NASA Astrophysics Data System (ADS)

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

    2008-10-01

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

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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.

  16. AhR sensing of bacterial pigments regulates antibacterial defence.

    PubMed

    Moura-Alves, Pedro; Faé, Kellen; Houthuys, Erica; Dorhoi, Anca; Kreuchwig, Annika; Furkert, Jens; Barison, Nicola; Diehl, Anne; Munder, Antje; Constant, Patricia; Skrahina, Tatsiana; Guhlich-Bornhof, Ute; Klemm, Marion; Koehler, Anne-Britta; Bandermann, Silke; Goosmann, Christian; Mollenkopf, Hans-Joachim; Hurwitz, Robert; Brinkmann, Volker; Fillatreau, Simon; Daffe, Mamadou; Tümmler, Burkhard; Kolbe, Michael; Oschkinat, Hartmut; Krause, Gerd; Kaufmann, Stefan H E

    2014-08-28

    The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns. PMID:25119038

  17. 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.

  18. 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

  19. 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.

  20. Rituximab therapy in nephrotic syndrome due to AH amyloidosis.

    PubMed

    Katoh, Nagaaki; Matsuda, Masayuki; Miyazaki, Daigo; Gono, Takahisa; Yazaki, Masahide; Ikeda, Shu-Ichi

    2009-01-01

    We report a patient with AH amyloidosis associated with lymphoplasmacytic leukemia that has remained in a stable state with a nephrotic syndrome for 17 months since the commencement of cyclic rituximab therapy aimed at suppression of pathogenetic gamma heavy chains. Free light chains in serum and CD20-positive cells in peripheral blood were useful as hematological markers in the patient. Rituximab might be a potent therapeutic option for AH amyloidosis associated with a B-cell lymphoproliferative disorder. PMID:19590993

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

    PubMed

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

    2014-11-01

    AH-7921 is a synthetic μ-opioid agonist, approximately equipotent with morphine. We report the death of two young individuals after ingestion of AH-7921 in combination with other psychoactive drugs. In the first case a young man died shortly after ingesting Internet drugs. Toxicological analysis of post mortem peripheral blood revealed AH-7921 (0.43 mg/L), 2-FMA (0.0069 mg/L) and 3-MMC (0.0021 mg/L) as well as codeine (0.42 mg/L), codeine-6-glucuronide (0.77 mg/L) and acetaminophen (18.7 mg/L). The second case involved a young female found dead at home. The only positive finding at medicolegal autopsy was needle marks. Toxicological analysis revealed AH-7921 (0.33 mg/L), methoxetamine (MXE) (0.064 mg/L), etizolam (0.27 mg/L), phenazepam (1.33 mg/L), 7-aminonitrazepam (0.043 mg/L), diazepam (0.046 mg/L), nordiazepam (0.073 mg/L), and oxazepam (0.018 mg/L) in blood. In both cases intoxication with AH-7921 in combination with other psychoactive drugs was considered to be the cause of death. PMID:25216892

  2. 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.

  3. 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

  4. 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.

  5. 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...

  6. Comparative epidemiology of human infections with avian influenza A(H7N9) and A(H5N1) viruses in China

    PubMed Central

    Cowling, Benjamin J.; Jin, Lianmei; Lau, Eric H. Y.; Liao, Qiaohong; Wu, Peng; Jiang, Hui; Tsang, Tim K.; Zheng, Jiandong; Fang, Vicky J.; Chang, Zhaorui; Ni, Michael Y.; Zhang, Qian; Ip, Dennis K. M.; Yu, Jianxing; Li, Yu; Wang, Liping; Tu, Wenxiao; Meng, Ling; Wu, Joseph T.; Luo, Huiming; Li, Qun; Shu, Yuelong; Li, Zhongjie; Feng, Zijian; Yang, Weizhong; Wang, Yu; Leung, Gabriel M.; Yu, Hongjie

    2013-01-01

    Background The novel influenza A(H7N9) virus recently emerged, while influenza A(H5N1) virus has infected humans since 2003 in mainland China. Both infections are thought to be predominantly zoonotic. We compared the epidemiologic characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China to date. Methods An integrated database was constructed with information on demographic, epidemiological, and clinical variables of laboratory-confirmed A(H7N9) and A(H5N1) cases that were reported to the Chinese Center for Disease Control and Prevention up to May 24, 2013. We described disease occurrence by age, sex and geography and estimated key epidemiologic parameters. Findings Among 130 and 43 patients with confirmed A(H7N9) and A(H5N1) respectively, the median ages were 62y and 26y. In urban areas, 74% of cases of both viruses were male whereas in rural areas the proportions were 62% for A(H7N9) and 33% for A(H5N1). Among cases of A(H7N9) and A(H5N1), 75% and 71% reported recent exposure to poultry. The mean incubation periods of A(H7N9) and A(H5N1) were 3.1 and 3.3 days, respectively. On average, 21 and 18 contacts were traced for each A(H7N9) case in urban and rural areas respectively; compared to 90 and 63 for A(H5N1). The hospitalization fatality risk was 35% (95% CI: 25%, 44%) for A(H7N9) and 70% (95% CI: 56%, 83%) for A(H5N1). Interpretation The sex ratios in urban compared to rural cases are consistent with poultry exposure driving the risk of infection. However the difference in susceptibility to serious illness with the two different viruses remains unexplained, given that most A(H7N9) cases were in older adults while most A(H5N1) cases were in younger individuals. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health. PMID:23803488

  7. Changes in the period of the eclipsing system AH Virginis

    NASA Astrophysics Data System (ADS)

    Kennedy, H. D.

    Guthnick and Prager (1929) discovered the variability of AH Virginis. On the basis of later observations, AH Virginis was classified as one of the few W UMa systems which display complete eclipses at an inclination likely to be closer to 90 deg than to 61 deg. Observations made in connection with the present study confirm constancy of light of 40 minutes duration during primary minimum. The present observations indicate curved as well as flat secondary minima. The variable was observed photoelectrically in yellow light with the 38-cm reflector during one night in April and five nights in May, 1981. A total of 73 observations defining primary minimum (ingress and egress), and 66 observations defining secondary minimum was obtained.

  8. Precursor systems analyses of automated highway systems. Activity area I. Impact of AHS on surrounding non-AHS roadways. Final report, September 1993-November 1994

    SciTech Connect

    Lima, P.; Wert, A.; Crowe, E.; O`Brien, S.; Roper, D.

    1995-05-01

    The study considers the influence which automated highway system (AHS) traffic would have on the conventional, non-automated freeway and street system as it approaches and departs from the automated roadway. The higher speeds and capacities possible with an AHS facility will attract traffic into the AHS lane from both the general purpose freeway lanes and the parallel arterials. The increased AHS traffic will have both positive and negative impacts on the surrounding street system. The analysis includes the modeling and evaluation of the operations of a freeway corridor with and without an AHS lane. Operations with and without an AHS lane on the surrounding roadways are then evaluated using traffic operations measures of effectiveness. The surrounding roadways include the general purpose freeway lanes, freeway ramps, parallel arterials, and cross streets. Additional modeling analyzes the impact of the AHS traffic on the cross streets. The Highway Capacity Software (HCS) program is used to evaluate the level-of-service on alternative configurations of the cross streets and parallel arterials. The physical requirements of the AHS lane and ramps are analyzed to determine the impact on the surrounding streets. The modeling results are also used as input to the Activity P analysis. Qualitative as well as quantitative impacts are addressed. AHS is reviewed from the perspective of an urban planner.

  9. 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

  10. Characterization of Peanut Germin-Like Proteins, AhGLPs in Plant Development and Defense

    PubMed Central

    Wang, Tong; Chen, Xiaoping; Zhu, Fanghe; Li, Haifen; Li, Ling; Yang, Qingli; Chi, Xiaoyuan; Yu, Shanlin; Liang, Xuanqiang

    2013-01-01

    Background Germin-like superfamily members are ubiquitously expressed in various plant species and play important roles in plant development and defense. Although several GLPs have been identified in peanut (Arachis hypogaea L.), their roles in development and defense remain unknown. In this research, we study the spatiotemporal expression of AhGLPs in peanut and their functions in plant defense. Results We have identified three new AhGLP members (AhGLP3b, AhGLP5b and AhGLP7b) that have distinct but very closely related DNA sequences. The spatial and temporal expression profiles revealed that each peanut GLP gene has its distinct expression pattern in various tissues and developmental stages. This suggests that these genes all have their distinct roles in peanut development. Subcellular location analysis demonstrated that AhGLP2 and 5 undergo a protein transport process after synthesis. The expression of all AhGLPs increased in responding to Aspergillus flavus infection, suggesting AhGLPs' ubiquitous roles in defense to A. flavus. Each AhGLP gene had its unique response to various abiotic stresses (including salt, H2O2 stress and wound), biotic stresses (including leaf spot, mosaic and rust) and plant hormone stimulations (including SA and ABA treatments). These results indicate that AhGLPs have their distinct roles in plant defense. Moreover, in vivo study of AhGLP transgenic Arabidopsis showed that both AhGLP2 and 3 had salt tolerance, which made transgenic Arabidopsis grow well under 100 mM NaCl stress. Conclusions For the first time, our study analyzes the AhGLP gene expression profiles in peanut and reveals their roles under various stresses. These results provide an insight into the developmental and defensive roles of GLP gene family in peanut. PMID:23626720

  11. 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.

  12. 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.

  13. AhNRAMP1 iron transporter is involved in iron acquisition in peanut.

    PubMed

    Xiong, Hongchun; Kobayashi, Takanori; Kakei, Yusuke; Senoura, Takeshi; Nakazono, Mikio; Takahashi, Hirokazu; Nakanishi, Hiromi; Shen, Hongyun; Duan, Penggen; Guo, Xiaotong; Nishizawa, Naoko K; Zuo, Yuanmei

    2012-07-01

    Peanut/maize intercropping is a sustainable and effective agroecosystem to alleviate iron-deficiency chlorosis. Using suppression subtractive hybridization from the roots of intercropped and monocropped peanut which show different iron nutrition levels, a peanut gene, AhNRAMP1, which belongs to divalent metal transporters of the natural resistance-associated macrophage protein (NRAMP) gene family was isolated. Yeast complementation assays suggested that AhNRAMP1 encodes a functional iron transporter. Moreover, the mRNA level of AhNRAMP1 was obviously induced by iron deficiency in both roots and leaves. Transient expression, laser microdissection, and in situ hybridization analyses revealed that AhNRAMP1 was mainly localized on the plasma membrane of the epidermis of peanut roots. Induced expression of AhNRAMP1 in tobacco conferred enhanced tolerance to iron deprivation. These results suggest that the AhNRAMP1 is possibly involved in iron acquisition in peanut plants. PMID:22611231

  14. 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).

  15. 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.

  16. Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line.

    PubMed

    Miyamoto, K; Wakabayashi, D; Minamino, T; Nomura, M; Wakusawa, S; Nakamura, S

    1996-01-01

    Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and clorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil. AH66 cells contained much glutahione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to clorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas. PMID:8702243

  17. 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

  18. 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

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

    PubMed

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

    2015-05-01

    The aryl hydrocarbon receptor (AhR) is well known as a ligand binding transcription factor regulating various biological effects. Previously we have shown that long-term exposure to estrogen in breast cancer cells caused not only down regulation of estrogen receptor (ER) but also overexpression of AhR. The AhR interacts with several cell signaling pathways associated with induction of tyrosine kinases, cytokines and growth factors which may support the survival roles of AhR escaping from apoptosis elicited by a variety of apoptosis inducing agents in breast cancer. In this study, we studied the anti-apoptotic role of AhR in different breast cancer cells when apoptosis was induced by exposure to UV light and chemotherapeutic agents. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in AhR overexpressing breast cancer cells effectively suppressed the apoptotic response induced by UV-irradiation, doxorubicin, lapatinib and paclitaxel. The anti-apoptotic response of TCDD was uniformly antagonized by the treatment with 3'methoxy-4'nitroflavone (MNF), a specific antagonist of AhR. TCDD's survival action of apoptosis was accompanied with the induction of well-known inflammatory genes, such as cyclooxygenase-2 (COX-2) and NF-κB subunit RelB. Moreover, TCDD increased the activity of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO), which metabolizes tryptophan to kynurenine (Kyn) and mediates tumor immunity. Kyn also acts as an AhR ligand like TCDD, and kyn induced an anti-apoptotic response in breast cancer cells. Accordingly, our present study suggests that AhR plays a pivotal role in the development of breast cancer via the suppression of apoptosis, and provides an idea that the use of AhR antagonists with chemotherapeutic agents may effectively synergize the elimination of breast cancer cells. PMID:25987214

  20. The NASA/AHS Rotorcraft Noise Reduction Program

    NASA Technical Reports Server (NTRS)

    Childress, Otis S., Jr.

    1988-01-01

    Research of the NASA/AHS noise reduction program is discussed, stressing work in four areas: noise prediction, testing and data base, noise reduction, and criteria development. A program called ROTONET has been developed, using a code structure divided into four main parts; main- and tail-rotor blade geometry, rotor performance, noise calculations, and noise propagation. Wind tunnel tests on individual rotors, and flight tests on a helicopter built specifically to generate a broadband main rotor noise data base have been conducted. In the field of noise reduction, researchers have performed analytical evaluations of low noise rotor concepts, and small-scale wind tunnel evaluations of noise reduction concepts. Under the supervision of the FAA, the program in conducting tests to develop criteria for helicopters and heliports.

  1. The tertiary structures of porcine AhR and ARNT proteins and molecular interactions within the TCDD/AhR/ARNT complex.

    PubMed

    Orlowska, Karina; Molcan, Tomasz; Swigonska, Sylwia; Sadowska, Agnieszka; Jablonska, Monika; Nynca, Anna; Jastrzebski, Jan P; Ciereszko, Renata E

    2016-06-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by structurally diverse synthetic and natural chemicals, including toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the present study, homology models of the porcine AhR-ligand binding domain (LBD) and the porcine aryl hydrocarbon receptor nuclear translocator-ligand binding domain (ARNT-LBD) were created on the basis of structures of closely related respective proteins i.e., human Hif-2α and ARNT. Molecular docking of TCDD to the porcine AhR-LBD model revealed high binding affinity (-8.8kcal/mol) between TCDD and the receptor. Moreover, formation of the TCDD/AhR-LBD complex was confirmed experimentally with the use of electrophoretic mobility shift assay (EMSA). It was found that TCDD (10nM, 2h of incubation) not only bound to the AhR in the porcine granulosa cells but also activated the receptor. The current study provides a framework for examining the key events involved in the ligand-dependent activation of the AhR. PMID:27288759

  2. Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif

    PubMed Central

    Yusufzai, Timur; Kadonaga, James T.

    2010-01-01

    The structure and integrity of DNA is of considerable biological and biomedical importance, and it is therefore critical to identify and to characterize enzymes that alter DNA structure. DNA helicases are ATP-driven motor proteins that unwind DNA. Conversely, HepA-related protein (HARP) protein (also known as SMARCAL1 and DNA-dependent ATPase A) is an annealing helicase that rewinds DNA in an ATP-dependent manner. To date, HARP is the only known annealing helicase. Here we report the identification of a second annealing helicase, which we term AH2, for annealing helicase 2. Like HARP, AH2 catalyzes the ATP-dependent rewinding of replication protein A (RPA)-bound complementary single-stranded DNA, but does not exhibit any detectable helicase activity. Unlike HARP, however, AH2 lacks a conserved RPA-binding domain and does not interact with RPA. In addition, AH2 contains an HNH motif, which is commonly found in bacteria and fungi and is often associated with nuclease activity. AH2 appears to be the only vertebrate protein with an HNH motif. Contrary to expectations, purified AH2 does not exhibit nuclease activity, but it remains possible that AH2 contains a latent nuclease that is activated under specific conditions. These structural and functional differences between AH2 and HARP suggest that different annealing helicases have distinct functions in the cell. PMID:21078962

  3. Equine Influenza A(H3N8) Virus Infection in Cats

    PubMed Central

    Su, Shuo; Wang, Lifang; Fu, Xinliang; He, Shuyi; Hong, Malin; Zhou, Pei; Gray, Gregory

    2014-01-01

    Interspecies transmission of equine influenza A(H3N8) virus has resulted in establishment of a canine influenza virus. To determine if something similar could happen with cats, we experimentally infected 14 cats with the equine influenza A(H3N8) virus. All showed clinical signs, shed virus, and transmitted the virus to a contact cohort. PMID:25417790

  4. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae

    PubMed Central

    Zi, Jiachen; Peters, Reuben J.

    2013-01-01

    Miltiradiene (1), is the precursor of phenolic diterpenoids such as ferruginol (2), requiring aromatization and hydroxylation. While this has been attributed to a single cytochrome P450 (CYP76AH1), characterization of the rosemary ortholog CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely oxidized aromatic intermediate abietatriene (3). PMID:24108414

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

    PubMed

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

    2013-06-01

    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

  6. IMMUNOHISTOCHEMICAL DOUBLE-STAINING FOR AH RECEPTOR AND ARNT IN HUMAN EMBRYONIC PALATAL SHELVES

    EPA Science Inventory

    The aryl hydrocarbon receptor (AhR) and the AhR nuclear translocation protein (ARNT) are helix-loop-helix (HLH) proteins involved in transcriptional regulation. olycyclic aromatic halogenated chemicals, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, bind ...

  7. 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

  8. 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.…

  9. 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

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

    PubMed

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

    2015-04-01

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

  11. 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

  12. 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

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

    PubMed

    Jeuken, Anoek; Keser, Bart J G; Khan, Elaine; Brouwer, Abraham; Koeman, Jan; Denison, Michael S

    2003-08-27

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by a structurally diverse range of synthetic and natural chemicals, and it mediates the toxic and biological effects of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The spectrum of chemicals that bind to and activate the AhR signal transduction pathway and the identity of materials containing AhR active chemicals is only now being defined. Utilizing AhR-dependent gel retardation and reporter gene bioassays, the screening of extracts of 22 dietary herbal supplements and 21 food products (vegetables and fruits) was performed to identify those containing AhR agonists. Several herbal extracts (ginseng, Fo-Ti, white oak bark, licorice, ginkgo biloba, and black cohosh) stimulated AhR DNA binding and gene expression to levels between 20 and 60% of that produced by TCDD. Although some food extracts (corn, jalapeño pepper, green bell pepper, apple, Brussels sprout, and potato) were relatively potent activators of AhR DNA binding (30-50% of TCDD), only corn and jalapeño pepper extracts induced AhR-dependent luciferase reporter gene expression. However, dilution of corn, jalapeño pepper, bell pepper, and potato extracts dramatically increased their ability to induce luciferase activity, suggesting that these extracts contained AhR antagonists whose effectiveness was overcome by dilution. Overall, these results demonstrate that dietary products can be a major source of naturally occurring AhR ligands to which animals and humans are chronically exposed. PMID:12926901

  14. Aryl Hydrocarbon Receptor (AhR) Regulates Silica-Induced Inflammation But Not Fibrosis

    PubMed Central

    Beamer, Celine A.; Seaver, Benjamin P.; Shepherd, David M.

    2012-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is responsible for mediating a variety of pharmacological and toxicological effects caused by halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, recent evidence has revealed that the AhR also has numerous physiological roles aside from xenobiotic metabolism, including regulation of immune and inflammatory signaling as well as normal development and homeostasis of several organs. To investigate the role of the AhR in crystalline silica (SiO2)–induced inflammation and fibrosis, C57Bl/6 and AhR−/− mice were exposed to SiO2 or vehicle. Similarly, C57Bl/6 mice were exposed to SiO2 and TCDD either simultaneously or sequentially to assess whether AhR activation alters inflammation and fibrosis. SiO2-induced acute lung inflammation was more severe in AhR−/− mice; however, the fibrotic response of AhR−/− mice was attenuated compared with C57Bl/6 mice. In a model of chronic SiO2 exposure, AhR activation by TCDD in C57Bl/6 mice resulted in reduced inflammation; however, the fibrotic response was not affected. Bone marrow–derived macrophages (BMM) from AhR−/− mice also produced higher levels of cytokines and chemokines in response to SiO2. Analysis of gene expression revealed that BMM derived from AhR−/− mice exhibit increased levels of pro-interleukin (IL)-1β, IL-6, and Bcl-2, yet decreased levels of signal transducers and activators of transcription (STAT)2, STAT5a, and serpin B2 (Pai-2) in response to SiO2. PMID:22273745

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

    PubMed Central

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

    2010-01-01

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

  16. Characterization of drug-resistant influenza virus A(H1N1) and A(H3N2) variants selected in vitro with laninamivir.

    PubMed

    Samson, Mélanie; Abed, Yacine; Desrochers, François-Marc; Hamilton, Stephanie; Luttick, Angela; Tucker, Simon P; Pryor, Melinda J; Boivin, Guy

    2014-09-01

    Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses under in vitro laninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant. In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistance in vitro. PMID:24957832

  17. 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.

  18. Nodulisporiviridins A-H, Bioactive Viridins from Nodulisporium sp.

    PubMed

    Zhao, Qin; Chen, Guo-Dong; Feng, Xiao-Lin; Yu, Yang; He, Rong-Rong; Li, Xiao-Xia; Huang, Yan; Zhou, Wen-Xia; Guo, Liang-Dong; Zheng, Yi-Zhi; Yao, Xin-Sheng; Gao, Hao

    2015-06-26

    Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. The structures were determined using spectroscopic and X-ray crystallographic analysis. Nodulisporiviridins A-D (1-4) are unique viridins with an opened ring A. The Aβ42 aggregation inhibitory activities of 1-8 were evaluated using a thioflavin T (ThT) assay with epigallocatechin gallate (EGCG) as the positive control (EGCG IC50 of 0.5 μM). Nodulisporiviridin G (7) displayed potent inhibitory activity with an IC50 value of 1.2 μM, and the preliminary trend of activity of these viridins as Aβ42 aggregation inhibitors was proposed. The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer's disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine). PMID:25978520

  19. Species-Specific Differential AhR Expression Protects Human Neural Progenitor Cells against Developmental Neurotoxicity of PAHs

    PubMed Central

    Gassmann, Kathrin; Abel, Josef; Bothe, Hanno; Haarmann-Stemmann, Thomas; Merk, Hans F.; Quasthoff, Kim N.; Rockel, Thomas Dino; Schreiber, Timm; Fritsche, Ellen

    2010-01-01

    Background Because of their lipophilicity, persistent organic pollutants (POPs) cross the human placenta, possibly affecting central nervous system development. Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators of AhR signaling. Therefore, AhR activation has been suggested to cause developmental neurotoxicity (DNT). Objective We studied the effects of AhR ligands on basic processes of brain development in two comparative in vitro systems to determine whether AhR-activation is the underlying mechanism for reported DNT of POPs in humans. Methods We employed neurosphere cultures based on human neural progenitor cells (hNPCs) and wild-type and AhR-deficient mouse NPCs (mNPCs) and studied the effects of different AhR agonists [3-methylcholanthrene (3-MC), benzo(a)pyrene [B(a)P], and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and an antagonist [3′-methoxy-4′-nitroflavone (MNF)] on neurosphere development. Moreover, we analyzed expression of AhR and genes involved in AhR signaling. Results In contrast to wild-type mNPCs, hNPCs and AhR-deficient mNPCs were insensitive to AhR agonism or antagonism. Although AhR modulation attenuated wild-type mNPC proliferation and migration, hNPCs and AhR-deficient mNPCs remained unaffected. Results also suggest that species-specific differences resulted from nonfunctional AhR signaling in hNPCs. Conclusion Our findings suggest that in contrast to wild-type mNPCs, hNPCs were protected against polycyclic aromatic hydrocarbon–induced DNT because of an absence of AhR. This difference may contribute to species-specific differences in sensitivity to POPs. PMID:20570779

  20. 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

  1. Coactivator recruitment of AhR/ARNT1.

    PubMed

    Endler, Alexander; Chen, Li; Shibasaki, Futoshi

    2014-01-01

    A common feature of nuclear receptors (NRs) is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of the specific genes in the nucleus. Another common feature of NRs is their dependence on coactivators, which bridge the basic transcriptional machinery and other cofactors to the target genes, in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase (HAT) function. In this review, we focus on our recent findings related to the recruitment of steroid receptor coactivator 1 (SRC1/NCoA1) by the estrogen receptor-α (ERα) and by the arylhydrocarbon receptor/arylhydrocarbon receptor nuclear translocator 1 (AhR/ARNT1) complex. We also describe the extension of our previously published findings regarding the binding between ARNT1.1 exon16 and SRC1e exon 21, via in silico analyses of androgen receptor (AR) NH2-carboxyl-terminal interactions, the results of which were verified by in vitro experiments. Based on these data, we suggest a newly derived tentative binding site of nuclear coactivator 2/glucocorticoid receptor interacting protein-1/transcriptional intermediary factor 2 (NCOA-2/ GRIP-1/TIF-2) for ARNT1.1 exon 16. Furthermore, results obtained by immunoprecipitation have revealed a second leucine-rich binding site for hARNT1.1 exon 16 in SRC1e exon 21 (LSSTDLL). Finally, we discuss the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an endocrine disruptor for estrogen related transcription. PMID:24950180

  2. 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.

  3. 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.

  4. Cloning of a factor required for activity of the Ah (dioxin) receptor

    SciTech Connect

    Hoffman, E.C.; Reyes, H.; Chu, Fongfong; Sander, F.; Conley, L.H.; Brooks, B.A.; Hankinson, O. )

    1991-05-17

    The aryl hydrocarbon (Ah) receptor binds various environmental pollutants, such as polycyclic aromatic hydrocarbons, heterocyclic amines, and polychlorinated aromatic compounds (dioxins, dibenzofurans, and biphenyls), and mediates the carcinogenic effects of these agents. The complementary DNA and part of the gene for an 87-kilodalton human protein that is necessary for Ah receptor function have been cloned. The protein is not the ligand-binding subunit of the receptor but is a factor that is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after binding ligand. The requirement for this factor distinguishes the Ah receptor from the glucocorticoid receptor, to which the Ah receptor has been presumed to be similar. Two portions of the 87-kilodalton protein share sequence similarities with two Drosophila proteins, Per and Sim. Another segment of the protein shows conformity to the consensus sequence for the basic helix-loop-helix motif found in proteins that bind DNA as homodimers or heterodimers.

  5. 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...

  6. 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

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

    PubMed

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

    2010-05-15

    The distribution of estrogen receptor (ERalpha) and Aryl Hydrocarbon Receptor (AhR) activities between the dissolved phase and suspended solids were investigated during wastewater treatment. Three wastewater treatment plants with different treatment technologies (waste stabilization ponds (WSPs), trickling filters (TFs) and activated sludge supplemented with a biofilter system (ASB)) were sampled. Estrogenic and AhR activities were detected in both phases in influents and effluents. Estrogenic and AhR activities in wastewater influents ranged from 41.8 to 79 ng/L E(2) Eq. and from 37.9 to 115.5 ng/L TCDD Eq. in the dissolved phase and from 5.5 to 88.6 ng/g E(2) Eq. and from 15 to 700 ng/g TCDD Eq. in the suspended solids. For both activities, WSP showed greater or similar removal efficiency than ASB and both were much more efficient than TF which had the lowest removal efficiency. Moreover, our data indicate that the efficiency of removal of ER and AhR activities from the suspended solid phase was mainly due to removal of suspended solids. Indeed, ER and AhR activities were detected in the effluent suspended solid phase indicating that suspended solids, which are usually not considered in these types of studies, contribute to environmental contamination by endocrine disrupting compounds and should therefore be routinely assessed for a better estimation of the ER and AhR activities released in the environment. PMID:20303573

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

    PubMed Central

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

    2014-01-01

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

  9. Tryptamine serves as a proligand of the AhR transcriptional pathway whose activation is dependent of monoamine oxidases.

    PubMed

    Vikström Bergander, Linda; Cai, Wen; Klocke, Bernward; Seifert, Martin; Pongratz, Ingemar

    2012-09-01

    The function of the aryl hydrocarbon receptor (AhR) in mediating the biological effect to environmental pollutants is well established. However, accumulated evidence indicates a wide range of physiological and pathological functions mediated by the AhR, suggesting the existence of endogenous AhR ligand(s). The nature of an AhR ligand remain elusive; however, it is known that the AhR is activated by several compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin or the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. In this study, we show that physiological concentrations of tryptamine (TA) lead to induction of cytochrome P4501A1 transcription through an AhR-dependent mechanism. In addition, we show that activation of the AhR by TA requires a functional monoamino oxidase system, suggesting that TA acts as an AhR proligand possibly by converting to a high-affinity AhR ligand. Taken together, we show a possible mechanism, through which AhR signaling is activated by endogenous conversion of TA involving monoamine oxidases. PMID:22865928

  10. 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. PMID:24406432

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

    PubMed

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

    2015-01-01

    In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627

  12. 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

  13. 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.

  14. 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. PMID:26108286

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

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. [Infection of pigs with influenza A/H4 and A/H5 viruses isolated from wild birds on the territory of Russia].

    PubMed

    Iamnikova, S S; Kurinov, G V; Lomakina, N F; Kurinov, V V; Fediakina, I T; Zaberezhnyĭ, A D; L'vov, D K

    2008-01-01

    Pigs were intranasally infected with avian influenza A/H5 (H5N1, H5N3) and A/H4 (H4N6, H4N8) viruses in mono- and coinfection. Infection with both apathogenic and pathogenic strains caused no clinical manifestations. A virus and/or fragments of its genome retained in nasopharyngeal fluid as long as 6-8 days after infection. During monoinfection, the structure of the hemagglutinin (HA) receptor site of isolates from the pigs infected with A/H5N1 strains (A/chicken/Kurgan/3/2005, A/duck/Russia/5354-vac/2005) and A/H5N3 (A/duck/Primorje/2633/01) remained unchanged during 6-7 days. When two animals infected with avirulent A/H5N3 viruses (A/duck/Primorje/2633/01, A/duck/Altai/1285/91) that differed in immunogenic properties were kept together, the A/duck/Altai/1285/91 virus that induced a later IgG generation was prevalent in the nasopharyngeal fluid of both animals. Moreover, 4 significant nucleotide replacements were detected in the HA gene on days 7-8. Infection of pigs with avian influenza A/H4 viruses yielded the similar results. The joint keeping of animals infected with Algarganey teal/Astrakhan/309/102 (H4N8) strain and A/ musk beaver/Buryatia/944/00 (H4N6) isolated from musk beaver exhibited fragments of "a variant" of the identical structure in the nasal swabs of both animals on days 7-8. A nucleotide sequence from 37 nucleotide replacements differing from both baseline sequences was revealed in the HA 364-1045 gene region. The amino acid sequence of the variant was similar to Algarganey teal/Astrakhan/3091/02, other than one position 264 < Lys > (numeration by H3), which coincided with the A/ musk beaver/Buryatia/1944/00 strain. The latter induced the antibody generation on day 5 after infection while the A/garganey teal/Astrakhan/3091/02 strain did only on day 14. It is possible that under co-circulation of two different influenza A viruses, the virus causing a slower development of an immune response showed a higher probability of transiting to another host

  18. Toward elucidation of dioxin-mediated chloracne and Ah receptor functions.

    PubMed

    Bock, Karl Walter

    2016-07-15

    Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and ß-Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and ß-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis. TCDD has been demonstrated to induce Blimp1 expression in the sebocyte stem/progenitor cell line SZ95, leading to sebocyte apoptosis and proliferation of interfollicular epidermis cells. These findings explain observations in TCDD-poisoned individuals, and identify target cells and molecular targets of dioxin-mediated chloracne. They clearly demonstrate that the AhR operates in a cell context-dependent manner, and provide hints to homeostatic functions of AhR in stem/progenitor cells. PMID:26801687

  19. Sealing properties of Ketac-Endo glass ionomer cement and AH26 root canal sealers.

    PubMed

    De Gee, A J; Wu, M K; Wesselink, P R

    1994-09-01

    Sealing capacity, setting shrinkage and setting time of a recently introduced glass ionomer cement Ketac-Endo were compared with that of a conventional sealer AH26. Sixty half-cylinders, 8 mm long, 4 mm in diameter, made from fresh bovine root dentine, had their smear layer removed before being cemented together while separated by 1-mm spacers. This resulted in a group of 15 cylinders cemented with Ketac-Endo and a similar group with AH26. After coating the lateral surface with nail varnish, one end of each cylinder was connected with a tube filled with water under 120 kPa (1.2 atm) pressure. At the other end the fluid leaking through the cemented interface of the cylinders was measured by displacement of an air bubble in an attached standard glass capillary. In this particular set-up where the sealers were used in bulk between two opposing dentine surfaces, Ketac-Endo leaked significantly more than AH26. After shear loading the cemented specimens, it was found that the area of adhesive failure was 88% for Ketac-Endo, and 15% for AH26. The leakage pathways were most probably at the dentine-sealer interface for Ketac-Endo and through cohesive fractures in the sealer for AH26. PMID:7814135

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

    PubMed

    Dudley, Joseph P; Mackay, Ian M

    2013-11-01

    We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations. PMID:24091087

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

    PubMed Central

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

    2016-01-01

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

  2. 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.

  3. 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.

  4. Pandemic influenza A/H1N1 and organ donation.

    PubMed

    Lattes, R; Jacob, N; de la Fuente, J; Fragale, G; Massari, P

    2010-04-01

    One of the concerns regarding the pandemic of novel influenza A/H1N1 virus is its potential to hamper transplant programs if the decision is made that organs from donors with influenza A/H1N1 should not be used. Evidence of transmissibility through organ transplantation is speculative at best. We report the outcome of 2 kidney transplant recipients who received kidneys from the same deceased donor, in whom the diagnosis of infection by the novel virus became available only after engraftment. The donor also had received a complete course of antiviral treatment before donation. The recipients were transplanted at 2 different facilities and were managed differently. Neither recipient developed flu syndrome, and both had an uneventful outcome. It is possible to speculate that kidneys from donors who have had confirmed influenza A/H1N1 and who have received antiviral treatment can be safely used in transplantation. PMID:20180928

  5. 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.

  6. 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

  7. 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

  8. AH7, a non-polyenic antifungal antibiotic produced by a new strain of Streptosporangium roseum.

    PubMed

    Hacène, H; Boudjellal, F; Lefebvre, G

    1998-01-01

    An antibiotic (AH7) produced by Streptosporangium roseum strain 214 was investigated. This compound was extracted with chloroform from the filtrate culture and purified using thin-layer chromatography and high pressure liquid chromatography procedures. The antibiotic strongly inhibited the growth of several strains of fungi and bacteria known to be plant and human pathogens. This compound differed from all other antibiotics known to be synthesized by Streptosporangium spp. Some of its chemical and physical properties resembled those of maytansines produced by Nocardia but the antibiotic AH7 has only antibacterial and antitumoral activities. PMID:10093231

  9. AH17, a new non-polyenic antifungal antibiotic produced by a strain of Spirillospora.

    PubMed

    Hacène, H; Lefebvre, G

    1995-01-01

    An antibiotic (AH17) was produced by Spirillospora strain 719. This substance was obtained only from the broth filtrate after precipitation with acetic acid followed by extraction with n-butanol. Its purification was carried out by thin layer chromatography on silica gel followed by HPLC procedures. It showed activity against Gram-positive and Gram-negative bacteria and fungi. The spectroscopic and chemical properties were examined and indicated that AH17 was a quinone. It seems that this is a new antibiotic from Spirillospora. PMID:8559083

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

    PubMed

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

    2013-01-01

    Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model. PMID:24069320

  11. 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

  12. Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly.

    PubMed

    Aguilar-Gurrieri, Carmen; Larabi, Amédé; Vinayachandran, Vinesh; Patel, Nisha A; Yen, Kuangyu; Reja, Rohit; Ebong, Ima-O; Schoehn, Guy; Robinson, Carol V; Pugh, B Franklin; Panne, Daniel

    2016-07-01

    Nap1 is a histone chaperone involved in the nuclear import of H2A-H2B and nucleosome assembly. Here, we report the crystal structure of Nap1 bound to H2A-H2B together with in vitro and in vivo functional studies that elucidate the principles underlying Nap1-mediated H2A-H2B chaperoning and nucleosome assembly. A Nap1 dimer provides an acidic binding surface and asymmetrically engages a single H2A-H2B heterodimer. Oligomerization of the Nap1-H2A-H2B complex results in burial of surfaces required for deposition of H2A-H2B into nucleosomes. Chromatin immunoprecipitation-exonuclease (ChIP-exo) analysis shows that Nap1 is required for H2A-H2B deposition across the genome. Mutants that interfere with Nap1 oligomerization exhibit severe nucleosome assembly defects showing that oligomerization is essential for the chaperone function. These findings establish the molecular basis for Nap1-mediated H2A-H2B deposition and nucleosome assembly. PMID:27225933

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

    ERIC Educational Resources Information Center

    Heim, A. W.; And Others

    1972-01-01

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

  14. Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): Structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus

    SciTech Connect

    Kerkvliet, N.I.; Baecher-Steppan, L.; Smith, B.B.; Youngberg, J.A.; Henderson, M.C.; Buhler, D.R. )

    1990-04-01

    Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. PRODUCTION AND CHARACTERIZATION OF MONOCLONAL ANTIBODIES DIRECTED AGAINST THE AH RECEPTOR

    EPA Science Inventory

    Six hybridomas secreting monoclonal antibodies that are specific for the N-terminal peptide sequence of the murine Ah receptor were isolated. hese antibodies bind with high specificity to the Al receptor on protein blots of Hepa 1c1c7 cytosol. hree IgG1 antibodies (Rpt1, 2, and 3...

  20. Hemagglutinin Receptor Binding of a Human Isolate of Influenza A(H10N8) Virus

    PubMed Central

    Mansour, Mena; Wohlbold, Teddy J.; Ermler, Megan E.; Hirsh, Ariana; Runstadler, Jonathan A.; Fernandez-Sesma, Ana

    2015-01-01

    Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 of these infected persons died. Characterization of the receptor binding pattern of H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors and maintain strong affinity for avian-like receptors. PMID:26079843

  1. Human Influenza A(H7N9) Virus Infection Associated with Poultry Farm, Northeastern China

    PubMed Central

    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

    2014-01-01

    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. PMID:25340624

  2. 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

  3. 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

  4. 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

  5. Binding of the Ah receptor to receptor binding factors in chromatin.

    PubMed

    Dunn, R T; Ruh, T S; Ruh, M F

    1993-03-01

    Dioxin induces biological responses through interaction with a specific intracellular receptor, the Ah receptor, and the subsequent interaction of the Ah receptor with chromatin. We report the binding of the Ah receptor, partially purified from rabbit liver, to receptor binding factors in chromatin. Rabbit liver chromatin proteins (CP) were isolated by adsorption of chromatin to hydroxylapatite followed by sequential extraction with 1-8 M GdnHCl. To assay for receptor binding a portion of each CP fraction was reconstituted to rabbit double-stranded DNA using a reverse gradient dialysis of 7.5 to 0 M GdnHCl. These reconstituted nucleoacidic proteins were then examined for binding to [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD)-receptor complexes by the streptomycin filter assay. Prior to the binding assay, [3H]TCDD-receptor complexes were partially purified by step elution from DEAE-cellulose columns. CP fractions 2, 5, and 7 were found to bind to the Ah receptor with high affinity. Scatchard analysis yielded Kd values in the nanomolar range. Competition with 2-fold excess unlabeled TCDD-receptor complexes was demonstrated, and binding was reduced markedly when the receptor was prepared in the presence of 10 mM molybdate. Such chromatin receptor binding factors (RBFs) may participate in the interaction of receptor with specific DNA sequences resulting in modulation of specific gene expression. PMID:8384852

  6. 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

  7. Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophora.

    PubMed

    Koyama, Koichiro; Hirasawa, Yusuke; Hosoya, Takahiro; Hoe, Teh Chin; Chan, Kit-Lam; Morita, Hiroshi

    2010-06-15

    Eight new indole alkaloids, alpneumines A-H (1-8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells. PMID:20576577

  8. 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...

  9. 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.

  10. Hemagglutinin Receptor Binding of a Human Isolate of Influenza A(H10N8) Virus.

    PubMed

    Ramos, Irene; Mansour, Mena; Wohlbold, Teddy J; Ermler, Megan E; Hirsh, Ariana; Runstadler, Jonathan A; Fernandez-Sesma, Ana; Krammer, Florian

    2015-07-01

    Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 of these infected persons died. Characterization of the receptor binding pattern of H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors and maintain strong affinity for avian-like receptors. PMID:26079843

  11. 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…

  12. 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

  13. Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).

    PubMed

    Oshida, Keiyu; Vasani, Naresh; Thomas, Russell S; Applegate, Dawn; Gonzalez, Frank J; Aleksunes, Lauren M; Klaassen, Curtis D; Corton, J Christopher

    2015-10-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dioxin-like compounds (DLC) as well as some drugs and endogenous tryptophan metabolites. Short-term activation of AhR can lead to hepatocellular steatosis, and chronic activation can lead to liver cancer in mice and rats. Analytical approaches were developed to identify biosets in a genomic database in which AhR activity was altered. A set of 63 genes was identified (the AhR gene expression biomarker) that was dependent on AhR for regulation after exposure to TCDD or benzo[a]pyrene and includes the known AhR targets Cyp1a1 and Cyp1b1. A fold-change rank-based test (Running Fisher's test; p-value ≤ 10(-4)) was used to evaluate the similarity between the AhR biomarker and a test set of 37 and 41 biosets positive or negative, respectively for AhR activation. The test resulted in a balanced accuracy of 95%. The rank-based test was used to identify factors that activate or suppress AhR in an annotated mouse liver/mouse primary hepatocyte gene expression database of ∼ 1850 comparisons. In addition to the expected activation of AhR by TCDD and DLC, AhR was activated by AP20189 and phenformin. AhR was suppressed by phenobarbital and 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) in a constitutive activated receptor (CAR)-dependent manner and pregnenolone-16α-carbonitrile in a pregnane X receptor (PXR)-dependent manner. Inactivation of individual genes in nullizygous models led to AhR activation (Pxr, Ghrhr, Taf10) or suppression (Ahr, Ilst6st, Hnf1a). This study describes a novel screening strategy for identifying factors in mouse liver that perturb AhR in a gene expression compendium. PMID:26215100

  14. High Rate of A(H1N1)pdm09 Infections among Rural Thai Villagers, 2009–2010

    PubMed Central

    Khuntirat, Benjawan; Yoon, In-Kyu; Chittaganpitch, Malinee; Krueger, Whitney S.; Supawat, Krongkaew; Blair, Patrick J.; Putnam, Shannon D.; Gibbons, Robert V.; Buddhari, Darunee; Sawanpanyalert, Pathom; Heil, Gary L.; Friary, John A.; Gray, Gregory C.

    2014-01-01

    Background Pandemic influenza A(H1N1)pdm09 emerged in Thailand in 2009. A prospective longitudinal adult cohort and household transmission study of influenza-like illness (ILI) was ongoing in rural Thailand at the time of emergence. Symptomatic and subclinical A(H1N1)pdm09 infection rates in the cohort and among household members were evaluated. Methods A cohort of 800 Thai adults underwent active community-based surveillance for ILI from 2008–2010. Acute respiratory samples from ILI episodes were tested for A(H1N1)pdm09 by qRT-PCR; acute and 60-day convalescent blood samples were tested by A(H1N1)pdm09 hemagglutination inhibition assay (HI). Enrollment, 12-month and 24-month follow-up blood samples were tested for A(H1N1)pdm09 seroconversion by HI. Household members of influenza A-infected cohort subjects with ILI were enrolled in household transmission investigations in which day 0 and 60 blood samples and acute respiratory samples were tested by either qRT-PCR or HI for A(H1N1)pdm09. Seroconversion between annual blood samples without A(H1N1)pdm09-positive ILI was considered as subclinical infection. Results The 2-yr cumulative incidence of A(H1N1)pdm09 infection in the cohort in 2009/2010 was 10.8% (84/781) with an annual incidence of 1.2% in 2009 and 9.7% in 2010; 83.3% of infections were subclinical (50% in 2009 and 85.9% in 2010). The 2-yr cumulative incidence was lowest (5%) in adults born ≤1957. The A(H1N1)pdm09 secondary attack rate among household contacts was 47.2% (17/36); 47.1% of these infections were subclinical. The highest A(H1N1)pdm09 secondary attack rate among household contacts (70.6%, 12/17) occurred among children born between 1990 and 2003. Conclusion Subclinical A(H1N1)pdm09 infections in Thai adults occurred frequently and accounted for a greater proportion of all A(H1N1)pdm09 infections than previously estimated. The role of subclinical infections in A(H1N1)pdm09 transmission has important implications in formulating strategies to

  15. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Powell, Joann B.; Ghotbaddini, Maryam

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

    Please cite this paper as: Friesema et al. (2012). Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients. Influenza and Other Respiratory Viruses 6(3), e16–e20. The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory‐confirmed Dutch cases were examined. An episode lasted a median of 7·5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. Severity of each symptom was rated highest in the first few days. Furthermore, diarrhoea was negatively associated with viral load, but not with faecal excretion of influenza virus. Cases with comorbidities appeared to have higher viral loads than the cases without, suggesting a less effective immune response. These results complement information obtained through traditional surveillance. PMID:22372759

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

    NASA Astrophysics Data System (ADS)

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

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

  1. 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.

  2. 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

  3. Leakage of AH26 and Ketac-Endo used with injected warm gutta-percha.

    PubMed

    Wu, M K; De Gee, A J; Wesselink, P R

    1997-05-01

    Condensing warm gutta-percha (GP) can greatly reduce the distance between the GP and the root canal walls (RCW). Different sealers with different film thicknesses may seal such close fits differently. With the use of a fluid transport model, leakage of AH26 and Ketac-Endo used with injected warm GP to fill root canals was measured. The distance between the condensed GP and RCW and the film thickness of the two sealers was determined as well. After condensation, the distance between GP and RCW was mostly less than 25 microns. AH26, with a film thickness of 39 microns, leaked more than Ketac-Endo (p < 0.05) of which the film thickness was 22 microns. It seems that film thickness of sealer is an influencing factor on the sealing ability of a root canal filling when condensation of thermoplasticized GP is performed. PMID:9545939

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

    PubMed

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

    2015-07-01

    Eight polyprenylated spirocyclic acylphloroglucinol derivatives (PSAPs), hyperascyrones A-H, were isolated from the aerial parts of Hypericum ascyron Linn., together with six known analogs. Their structures were established by spectroscopic analyses including HRESIMS, 1D and 2D NMR, and their absolute configurations were determined by electronic circular dichroism calculations (ECD, Gaussian 09). Structures of previously reported tomoeones C, D, G, and H were revised. Hyperascyrones A-H were evaluated for their cytotoxic and anti-HIV-1 activities, with hyperascyrones C and G exhibiting significant cytotoxicities against HL-60 cell lines with IC50 values of 4.22 and 8.36 μM, respectively. In addition, the chemotaxonomic significance of these compounds was also discussed. PMID:25800107

  5. 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

  6. Plan, formulate, and discuss a NASTRAN finite element model of the AH-64A helicopter airframe

    NASA Technical Reports Server (NTRS)

    Christ, Richard A.; Ferg, Douglas A.; Kilroy, Kevin A.; Toossi, Mostafa; Weisenburger, Richard K.

    1990-01-01

    A discussion of modeling plan objectives, followed by a description of the AH-64A aircraft including all general features, major components, and primary and structure definitions are presented. Following the aircraft description, a discussion of the modeling guidelines and model checkout procedure are provided. The NASTRAN finite element analysis is set up to be suitable to predict both static internal loads and vibrations. Finally, the results, schedule, and planned versus actual manhours for this work are presented.

  7. Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review

    PubMed Central

    Boëlle, Pierre‐Yves; Ansart, Séverine; Cori, Anne; Valleron, Alain‐Jacques

    2011-01-01

    Please cite this paper as: Boëlle P‐Y et al. (2011) Transmission parameters of the A/H1N1 (2009) influenza virus pandemic: a review. Influenza and Other Respiratory Viruses 5(5), 306–316. Background  The new influenza virus A/H1N1 (2009), identified in mid‐2009, rapidly spread over the world. Estimating the transmissibility of this new virus was a public health priority. Methods  We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection. Results  Thirteen studies documented the serial interval from household or close‐contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days. Model‐based estimates were more variable, from 1·9 to 6 days. Twenty‐four studies reported reproduction numbers for community‐based epidemics at the town or country level. The range was 1·2–3·1, with larger estimates reported at the beginning of the pandemic. Accounting for under‐reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5. Discussion  The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu. The estimates of the reproduction number were more variable. Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957). PMID:21668690

  8. LEO life tests on a 75 Ah bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Lenhart, S.; Koehler, C.; Applewhite, A.

    1988-01-01

    The design, building, and testing of an actively cooled 10-cell 75-Ah bipolar nickel/hydrogen battery are discussed. During the last 1000 cycles, the battery has shown some evidence of elecrical performance degradation. In particular, EOC and EOD voltages have increased and decreased by several millivolts, respectively, and deep discharge capacities to a 1.0 V/cell average cutoff voltage have decreased.

  9. 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.

  10. Life evaluation of 35Ah Ni-Cd cell in Japan

    NASA Technical Reports Server (NTRS)

    Kuwajima, S.; Kamimori, Nolimits; Nakatani, Ken

    1992-01-01

    The National Space Development Agency of Japan (NASDA) began developing Nickel-Cadmium (Ni-Cd) cells for space use in 1985. Sanyo Electric was responsible for the cell design, manufacturing, and initial testing. The cell life was evaluated by NASDA in the Tsukuba Space Center (TKSC). The development is presently in the qualification Test (QT) phase. Recent life-cycle data for 35 Ah Ni-Cd cells are presented.

  11. 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

  12. Hospitalization in two waves of pandemic influenza A(H1N1) in England.

    PubMed

    Campbell, C N J; Mytton, O T; McLean, E M; Rutter, P D; Pebody, R G; Sachedina, N; White, P J; Hawkins, C; Evans, B; Waight, P A; Ellis, J; Bermingham, A; Donaldson, L J; Catchpole, M

    2011-10-01

    Uncertainties exist regarding the population risks of hospitalization due to pandemic influenza A(H1N1). Understanding these risks is important for patients, clinicians and policy makers. This study aimed to clarify these uncertainties. A national surveillance system was established for patients hospitalized with laboratory-confirmed pandemic influenza A(H1N1) in England. Information was captured on demographics, pre-existing conditions, treatment and outcomes. The relative risks of hospitalization associated with pre-existing conditions were estimated by combining the captured data with population prevalence estimates. A total of 2416 hospitalizations were reported up to 6 January 2010. Within the population, 4·7 people/100,000 were hospitalized with pandemic influenza A(H1N1). The estimated hospitalization rate of cases showed a U-shaped distribution with age. Chronic kidney disease, chronic neurological disease, chronic respiratory disease and immunosuppression were each associated with a 10- to 20-fold increased risk of hospitalization. Patients who received antiviral medication within 48 h of symptom onset were less likely to be admitted to critical care than those who received them after this time (adjusted odds ratio 0·64, 95% confidence interval 0·44-0·94, P=0·024). In England the risk of hospitalization with pandemic influenza A(H1N1) has been concentrated in the young and those with pre-existing conditions. By quantifying these risks, this study will prove useful in planning for the next winter in the northern and southern hemispheres, and for future pandemics. PMID:21108872

  13. 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

  14. Influenza A(H6N1) Virus in Dogs, Taiwan

    PubMed Central

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

    2015-01-01

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

  15. 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

  16. Down regulation of hepatic PPARalpha function by AhR ligand.

    PubMed

    Shaban, Zein; El-Shazly, Samir; Abdelhady, Shawky; Fattouh, Ibrahim; Muzandu, Kaampwe; Ishizuka, Mayumi; Kimura, Kazuhiro; Kazusaka, Akio; Fujita, Shoichi

    2004-11-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Peroxisome proliferator activated receptor alpha (PPARalpha) is a nuclear receptor involved in the maintenance of lipid and glucose homeostasis. In this study we hypothesized that one of the possible mechanisms for the effect of TCDD and its related chemicals on fat metabolism could be through down regulation of PPARalpha functions. We treated Wistar rats with an AhR ligand, Sudan III (S.III), and/or PPARalpha ligand, Clofibric Acid (CA), for 3 days. We analysed the expression of one of the PPARalpha-target gene products, CYP4A protein and its mRNA. We also tested HepG2 cells with the afore-mentioned treatments and evaluated their effects on PPARalpha and RXRalpha protein. Treatment of Wistar rats with S.III was found to down regulates CYP4A protein expression and reduced its induction with CA. It also decreased mRNA expressions of CYP4A1, CYP4A2, CYP4A3 and PPARalpha. In HepG2 cells, PPARalpha and RXRalpha protein expression was decreased by S.III treatment in a dose dependent manner. Our results suggest that AhR has an inhibitory effect on PPARalpha function and a new pathway by which AhR ligands could disturb lipid metabolism. PMID:15585952

  17. Safety and Immunogenicity of a Single Low Dose or High Dose of Clade 2 Influenza A(H5N1) Inactivated Vaccine in Adults Previously Primed With Clade 1 Influenza A(H5N1) Vaccine.

    PubMed

    Winokur, Patricia L; Patel, Shital M; Brady, Rebecca; Chen, Wilbur H; El-Kamary, Samer S; Edwards, Kathryn; Creech, C Buddy; Frey, Sharon; Keitel, Wendy A; Belshe, Robert; Walter, Emmanuel; Bellamy, Abbie; Hill, Heather

    2015-08-15

    Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-μg or 90-μg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine. PMID:25712967

  18. 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

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

    PubMed

    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

  20. 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.

  1. Evaluation of the apical sealing ability of bioceramic sealer, AH plus & epiphany: An in vitro study

    PubMed Central

    Pawar, Suprit Sudhir; Pujar, Madhu Ajay; Makandar, Saleem Dadapeer

    2014-01-01

    Objective: This in vitro study evaluated and compared the microleakage of three sealers; Endosequence bioceramic (BC) sealer, AH Plus and Epiphany. Materials and Methods: Study was done on 75 extracted human single rooted permanent teeth, which were decoronated and the root canals were instrumented. The specimens were randomly divided into three groups (n = 25) and obturated by continuous wave condensation technique. Group A: using Endosequence BC, Group B: using AH Plus sealer, Group C: using Resilon Epiphany system. Microleakage was evaluated using dye penetration method. Teeth were split longitudinally and then horizontally markings were made at 2, 4 and 6 mm from the apex. Dye penetration evaluation was done under stereomicroscope (30X magnification). Results: The dye penetration in Group B was more than in Group A and C in both vertical and horizontal directions, suggesting that newly introduced BC sealer and Epiphany sealer sealed the root canal better compared to AH Plus Sealer. Conclusion: Newer root canal sealers seal the root canal better but cannot totally eliminate leakage. PMID:25506149

  2. 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.

  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. Structure and receptor binding preferences of recombinant human A(H3N2) virus hemagglutinins.

    PubMed

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

    2015-03-01

    A(H3N2) influenza viruses have circulated in humans since 1968, and antigenic drift of the hemagglutinin (HA) protein continues to be a driving force that allows the virus to escape the human immune response. Since the major antigenic sites of the HA overlap into the receptor binding site (RBS) of the molecule, the virus constantly struggles to effectively adapt to host immune responses, without compromising its functionality. Here, we have structurally assessed the evolution of the A(H3N2) virus HA RBS, using an established recombinant expression system. Glycan binding specificities of nineteen A(H3N2) influenza virus HAs, each a component of the seasonal influenza vaccine between 1968 and 2012, were analyzed. Results suggest that while its receptor-binding site has evolved from one that can bind a broad range of human receptor analogs to one with a more restricted binding profile for longer glycans, the virus continues to circulate and transmit efficiently among humans. PMID:25617824

  5. 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 ...

  6. 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

  7. Introducing the “TCDD-Inducible AhR-Nrf2 Gene Battery”

    PubMed Central

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

    2009-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the “AhR gene battery.” However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 μg/kg, ip) to Nrf2-null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid–synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice. PMID:19474220

  8. 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

  9. 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

  10. 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. PMID:26302041

  11. Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China

    PubMed Central

    Xu, Cuiling; Havers, Fiona; Wang, Lijie; Chen, Tao; Shi, Jinghong; Wang, Dayan; Yang, Jing; Yang, Lei; Widdowson, Marc-Alain

    2013-01-01

    In China during March 4–April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical. PMID:23879887

  12. 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

  13. 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

  14. Measurement of antibodies to avian influenza virus A(H7N7) in humans by hemagglutination inhibition test.

    PubMed

    Meijer, Adam; Bosman, Arnold; van de Kamp, Esther E H M; Wilbrink, Berry; Du Ry van Beest Holle, Mirna; Koopmans, Marion

    2006-03-01

    During the epizootic of highly pathogenic avian influenza A(H7N7) in 2003 in The Netherlands, RT-PCR and culture confirmed infection was detected in 89 persons who were ill. A modified hemagglutination inhibition (HI) test using horse erythrocytes and 2 hemagglutinating units of virus was applied to assess retrospectively the extent of human (subclinical) infection. Validation of the HI-test with sera from 34 RT-PCR and culture confirmed A(H7) infected persons and sera from 100 persons from a human influenza vaccine trial in autumn 2002 showed that this HI-test had a sensitivity of 85% and a specificity of 100% when using a cut-off titer of > or =10. Using this cut-off value, A(H7) specific antibodies were detected in 49% of 508 persons exposed to poultry and in 64% of 63 persons exposed to A(H7) infected persons. Correlation of seropositivity with the occurrence of eye symptoms in exposed persons who had not received antiviral prophylaxis and of reduced seropositivity with taking antiviral prophylaxis provided further evidence that the A(H7) HI antibody titers were real. In conclusion, by applying an HI-test using horse erythrocytes human antibodies against the avian A(H7N7) virus were detected with high sensitivity and specificity in an unexpectedly high proportion of exposed persons. PMID:16271401

  15. 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

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

    PubMed

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

    2016-01-01

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

  17. 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

  18. 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

  19. Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin.

    PubMed

    Lin, Yi Pu; Xiong, Xiaoli; Wharton, Stephen A; Martin, Stephen R; Coombs, Peter J; Vachieri, Sebastien G; Christodoulou, Evangelos; Walker, Philip A; Liu, Junfeng; Skehel, John J; Gamblin, Steven J; Hay, Alan J; Daniels, Rodney S; McCauley, John W

    2012-12-26

    The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). By 2001, the avidity of human H3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. These changes in receptor binding, which correlate with increased difficulties in virus propagation in vitro and in antigenic analysis, have been assessed by virus hemagglutination of erythrocytes from different species and quantified by measuring virus binding to receptor analogs using surface biolayer interferometry. Crystal structures of HA-receptor analog complexes formed with HAs from viruses isolated in 2004 and 2005 reveal significant differences in the conformation of the 220-loop of HA1, relative to the 1968 structure, resulting in altered interactions between the HA and the receptor analog that explain the changes in receptor affinity. Site-specific mutagenesis shows the HA1 Asp-225→Asn substitution to be the key determinant of the decreased receptor binding in viruses circulating since 2005. Our results indicate that the evolution of human influenza A(H3N2) viruses since 1968 has produced a virus with a low propensity to bind human receptor analogs, and this loss of avidity correlates with the marked reduction in A(H3N2) virus disease impact in the last 10 y. PMID:23236176

  20. 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

  1. Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.

    PubMed

    Zúñiga, J; Buendía-Roldán, I; Zhao, Y; Jiménez, L; Torres, D; Romo, J; Ramírez, G; Cruz, A; Vargas-Alarcon, G; Sheu, C-C; Chen, F; Su, L; Tager, A M; Pardo, A; Selman, M; Christiani, D C

    2012-03-01

    The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity. PMID:21737555

  2. 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. PMID:26765287

  3. 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.

  4. Investigation of difficult component effects on FEM vibration prediction for the AH-1G helicopter

    NASA Technical Reports Server (NTRS)

    Dompka, Robert V.

    1988-01-01

    Under the NASA-sponsored Design Analysis Methods for Vibrations program, a series of ground vibration tests and NASTRAN finite element model correlations were conducted on the Bell AH-1G helicopter gunship to investigate the effects of difficult components on the vibration response of the airframe. Secondary structure and damping were found to have significant effects on the frequency response of the airframe above 15 Hz. The nonlinear effects of thrust stiffening and elastomeric mounts on the low-frequency pylon modes below the main rotor were also significant.

  5. Performance features of 22-cell, 19Ah single pressure vessel nickel hydrogen battery

    NASA Technical Reports Server (NTRS)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    1996-01-01

    Two 22-cells 19Ah Nickel-Hydrogen (Ni-H2) Single Pressure Vessel (SPV) Qual batteries, one each from EPI/Joplin and EPI/Butler, were designed and procured. The two batteries differ in the cell encapsulation technology, stack preload, and activation procedure. Both the Butler and Joplin batteries met the specified requirements when subjected to qualification testing and completed 2100 and 1300 LEO cycles respectively, with nominal performance. This paper discusses advantages, design features, testing procedures, and results of the two single pressure vessel Ni-H2 batteries.

  6. Correlation of AH-1G airframe test data with a NASTRAN mathematical model

    NASA Technical Reports Server (NTRS)

    Cronkhite, J. D.; Berry, V. L.

    1976-01-01

    Test data was provided for evaluating a mathematical vibration model of the Bell AH-1G helicopter airframe. The math model was developed and analyzed using the NASTRAN structural analysis computer program. Data from static and dynamic tests were used for comparison with the math model. Static tests of the fuselage and tailboom were conducted to verify the stiffness representation of the NASTRAN model. Dynamic test data were obtained from shake tests of the airframe and were used to evaluate the NASTRAN model for representing the low frequency (below 30 Hz) vibration response of the airframe.

  7. 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

  8. Remodeling of Hyperpolarization-Activated Current, Ih, in Ah-Type Visceral Ganglion Neurons Following Ovariectomy in Adult Rats

    PubMed Central

    Xu, Wen-Xiao; Yan, Zhen-Yu; Liu, Yang; Zhou, Jia-Ying; Zhang, Hao-Cheng; Wang, Li-Juan; Pan, Xiao-Dong; Fu, Yili

    2013-01-01

    Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A− and Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX) has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage ‘sag’ as well as ‘rebound’ action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats. PMID:23951107

  9. Quantitative autoradiography of brain binding sites for the vesicular acetylcholine transport blocker 2-(4-phenylpiperidino)cyclohexanol (AH5183)

    SciTech Connect

    Marien, M.R.; Parsons, S.M.; Altar, C.A.

    1987-02-01

    2-(4-Phenylpiperidino)cyclohexanol (AH5183) is a noncompetitive and potent inhibitor of high-affinity acetylcholine transport into cholinergic vesicles. It is reported here that (/sup 3/H)AH5183 binds specifically and saturably to slide-mounted sections of the rat forebrain (Kd = 1.1 to 2.2 X 10(-8) M; Bmax = 286 to 399 fmol/mg of protein). The association and dissociation rate constants for (/sup 3/H)AH5183 binding are 8.6 X 10(6) M-1 X min-1 and 0.18 min-1, respectively. Bound (/sup 3/H)AH5183 can be displaced by nonradioactive AH5183 and by the structural analog (2 alpha,3 beta,4A beta,8A alpha)-decahydro-3-(4-phenyl-1-piperidinyl)-2- naphthalenol but not by 10 microM concentrations of the cholinergic drugs acetylcholine, choline, atropine, hexamethonium, eserine, or hemicholinium-3 or by the structurally related compounds 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridine, (+/-)-N-allylnormetazocine (SKF 10,047), levoxadrol, or dexoxadrol. Quantitative autoradiography reveals that (/sup 3/H)AH5183 binding sites are distributed heterogenously throughout the rat forebrain and are highly localized to cholinergic nerve terminal regions. At the level of the caudate nucleus-putamen, the highest concentrations of saturable (/sup 3/H)AH5183 binding (713-751 fmol/mg of protein) are found in the vertical limb of the diagonal band and the olfactory tubercle, with lesser amounts (334-516 fmol/mg of protein) in the caudate-putamen, nucleus accumbens, superficial layers of the cerebral cortex, and the primary olfactory cortex. At day 7 after transsection of the left fimbria, (/sup 3/H)AH5183 binding and choline acetyltransferase activity in the left hippocampus were reduced by 33 +/- 6% and 61 +/- 7%, respectively. These findings indicate that (/sup 3/H)AH5183 binds to a unique recognition site in rat brain that is topographically associated with cholinergic nerve terminals.

  10. 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

  11. 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

  12. 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.

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

    NASA Technical Reports Server (NTRS)

    Smithrick, John J.; Hall, Stephen W.

    1993-01-01

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

  14. 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.

  15. Partial purification and characterization of lipase from Geobacillus stearothermophilus AH22.

    PubMed

    Ekinci, Arife Pınar; Dinçer, Barbaros; Baltaş, Nimet; Adıgüzel, Ahmet

    2016-01-01

    The lipase was partially purified by ion exchange chromatography and gel filtration column chromatography, and was characterized from Geobacillus stearothermophilus AH22 strain. The lipase was purified 18.3-folds with 19.7% recovery. The lipase activity was determined by using p-nitrophenyl esters (C2-C12) as substrates. The Km values of the enzyme for these substrates were found as 0.16, 0.02, 0.19 and 0.55 mM, respectively, while Vmax values were 0.52, 1.03, 0.72 and 0.15 U mg(-1). The enzyme showed maximum activity at 50 °C and between pH 8.0 and 9.0. The enzyme was found to be quite stable at pH range of 4.0-10.0, and thermal stability between 50 and 60 °C. It was found that the best inhibitory effect of the enzyme activity was of Hg(2+). The inhibitory effect as orlistat, catechin, propyl paraben, p-coumaric acid, 3,4-dihydroxy hydro-cinnamic acid was examined. These results suggest that G. stearothermophilus AH22 lipase presents very suitable properties for industrial applications. PMID:25798692

  16. 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.

  17. Metapopulation Dynamics Enable Persistence of Influenza A, Including A/H5N1, in Poultry

    PubMed Central

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

    2013-01-01

    Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified. PMID:24312455

  18. 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.

  19. Neuroinvasive influenza virus A(H5N8) in fattening ducks, Hungary, 2015.

    PubMed

    Bányai, Krisztián; Bistyák, Andrea Tóthné; Thuma, Ákos; Gyuris, Éva; Ursu, Krisztina; Marton, Szilvia; Farkas, Szilvia L; Hortobágyi, Eleonóra; Bacsadi, Árpád; Dán, Ádám

    2016-09-01

    Highly pathogenic avian influenza (HPAI) A virus H5N8 was detected in far east Asian countries during 2014 and emerged in late 2014 in European countries. Hungary reported a HPAI A(H5N8) outbreak during late winter of 2015 at a Pekin duck fattening facility. Epidemiologic monitoring was extended to holdings in neighboring areas and nearby habitats used by wild birds but failed to identify the source of infection. In addition to respiratory symptoms, the affected birds showed lethargy and neuronal signs, including torticollis. Consistent with this finding, influenza A virus antigen was detected in large quantity in the brain. Molecular analysis of the identified strain showed very close genetic relationship (and >99% nucleotide sequence identity) with co-circulating HPAI A(H5N8) strains. A number of unique or rarely detected amino acid changes was detected in the HA (T220I, R512G), the M2 (I39M), the NA (T211I), the NS1 (P85T), and the PB2 (I261V) proteins of the Hungarian strain. Further studies are needed to demonstrate whether any of these mutations can be linked to neuroinvasiveness and neurovirulence in ducks. PMID:27215706

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

    PubMed

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

    2013-01-01

    Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified. PMID:24312455

  1. [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. PMID:20721445

  2. Photometric Study of AH Cancri, a W UMa-Type System in M67

    NASA Astrophysics Data System (ADS)

    Zhang, X. B.; Zhang, R. X.; Deng, L.

    2005-02-01

    We present time-series CCD photometry of AH Cnc, a W UMa-type binary system in the old open cluster M67. Over 3500 measurements in two filters were recorded on 15 nights from 2001 to 2004. From the data, 17 new times of minima for the eclipsing binary were obtained, from which a new ephemeris was derived. The orbital period of the system is refined as 0.36045754 days. A photometric analysis for the obtained light curves is performed based on the Wilson-Devinney code. The photometric solutions reveal a totally eclipsing contact configuration for AH Cnc. The photometric mass ratio is determined to be 0.149+/-0.002. The masses and radii of the components are estimated as 1.21+/-0.08 Msolar and 1.36+/-0.03 Rsolar for the primary and 0.18+/-0.02 Msolar and 0.62+/-0.02 Rsolar for the secondary, respectively. The evolutionary status of the contact system is briefly discussed.

  3. Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease

    PubMed Central

    Benoit, Anne; Beran, Jiri; Devaster, Jeanne-Marie; Esen, Meral; Launay, Odile; Leroux-Roels, Geert; McElhaney, Janet E.; Oostvogels, Lidia; van Essen, Gerrit A.; Gaglani, Manjusha; Jackson, Lisa A.; Vesikari, Timo; Legrand, Catherine; Tibaldi, Fabian; Innis, Bruce L.; Dewé, Walthère

    2015-01-01

    Background. To investigate the relationship between hemagglutinin-inhibition (HI) antibody levels to the risk of influenza disease, we conducted a correlate of protection analysis using pooled data from previously published randomized trials. Methods. Data on the occurrence of laboratory-confirmed influenza and HI levels pre- and postvaccination were analyzed from 4 datasets: 3 datasets included subjects aged <65 years who received inactivated trivalent influenza vaccine (TIV) or placebo, and 1 dataset included subjects aged ≥65 years who received AS03-adjuvanted TIV (AS03-TIV) or TIV. A logistic model was used to evaluate the relationship between the postvaccination titer of A/H3N2 HI antibodies and occurrence of A/H3N2 disease. We then built a receiver-operating characteristic curve to identify a potential cutoff titer between protection and no protection. Results. The baseline odds ratio of A/H3N2 disease was higher for subjects aged ≥65 years than <65 years and higher in seasons of strong epidemic intensity than moderate or low intensity. Including age and epidemic intensity as covariates, a 4-fold increase in titer was associated with a 2-fold decrease in the risk of A/H3N2 disease. Conclusions. The modeling exercise confirmed a relationship between A/H3N2 disease and HI responses, but it did not allow an evaluation of the predictive power of the HI response. PMID:26180823

  4. 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

  5. Modelling influenza A(H1N1) 2009 epidemics using a random network in a distributed computing environment.

    PubMed

    González-Parra, Gilberto; Villanueva, Rafael-J; Ruiz-Baragaño, Javier; Moraño, Jose-A

    2015-03-01

    In this paper we propose the use of a random network model for simulating and understanding the epidemics of influenza A(H1N1). The proposed model is used to simulate the transmission process of influenza A(H1N1) in a community region of Venezuela using distributed computing in order to accomplish many realizations of the underlying random process. These large scale epidemic simulations have recently become an important application of high-performance computing. The network model proposed performs better than the traditional epidemic model based on ordinary differential equations since it adjusts better to the irregularity of the real world data. In addition, the network model allows the consideration of many possibilities regarding the spread of influenza at the population level. The results presented here show how well the SEIR model fits the data for the AH1N1 time series despite the irregularity of the data and returns parameter values that are in good agreement with the medical data regarding AH1N1 influenza virus. This versatile network model approach may be applied to the simulation of the transmission dynamics of several epidemics in human networks. In addition, the simulation can provide useful information for the understanding, prediction and control of the transmission of influenza A(H1N1) epidemics. PMID:25559047

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

    PubMed

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

    2016-06-01

    IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs. PMID:27000947

  7. 2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals.

    PubMed

    Rondy, M; Launay, O; Puig-Barberà, J; Gefenaite, G; Castilla, J; de Gaetano Donati, K; Galtier, F; Hak, E; Guevara, M; Costanzo, S; Moren, A

    2015-01-01

    While influenza vaccines aim to decrease the incidence of severe influenza among high-risk groups, evidence of influenza vaccine effectiveness (IVE) among the influenza vaccine target population is sparse. We conducted a multicentre test-negative case-control study to estimate IVE against hospitalised laboratory-confirmed influenza in the target population in 18 hospitals in France, Italy, Lithuania and the Navarre and Valencia regions in Spain. All hospitalised patients aged ≥18 years, belonging to the target population presenting with influenza-like illness symptom onset within seven days were swabbed. Patients positive by reverse transcription polymerase chain reaction for influenza virus were cases and those negative were controls. Using logistic regression, we calculated IVE for each influenza virus subtype and adjusted it for month of symptom onset, study site, age and chronic conditions. Of the 1,972 patients included, 116 were positive for influenza A(H1N1)pdm09, 58 for A(H3N2) and 232 for influenza B. Adjusted IVE was 21.3% (95% confidence interval (CI): -25.2 to 50.6; n=1,628), 61.8% (95% CI: 26.8 to 80.0; n=557) and 43.1% (95% CI: 21.2 to 58.9; n=1,526) against influenza A(H1N1) pdm09, A(H3N2) and B respectively. Our results suggest that the 2012/13 IVE was moderate against influenza A(H3N2) and B and low against influenza A(H1N1) pdm09. PMID:25613779

  8. Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins.

    PubMed

    Wakusawa, S; Nakamura, S; Miyamoto, K

    1997-01-01

    A resistant subline (AH130/5A) selected from rat hepatoma AH130 cells after exposure to adriamycin (ADM) showed remarkable resistance to multiple antitumor drugs, including mitomycin C (MMC) and porfiromycin (PFM). PFM, vinblastine (VLB), and ADM accumulated in AH130/5A far less than in the parent AH130 (AH130/P) cells. AH130/5A cells showed overexpression of P-glycoprotein (PGP), an increase in glutathione S-transferase activity, and a decrease in DT-diaphorase and glutathione peroxidase activity. The resistance to MMC and VLB of AH130/5A cells was partly reversed by H-87, an inhibitor of PGP. Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells. Dicumarol, an inhibitor of DT-diaphorase, decreased PFM uptake and reduced the growth-inhibitory action of MMC in AH130/P cells. These results indicated that the adriamycin treatment of hepatoma cells caused multifactorial multidrug resistance involving a decrease in DT-diaphorase activity. PMID:9045901

  9. Detection of the TCDD Binding-Fingerprint within the Ah Receptor Ligand Binding Domain by Structurally Driven Mutagenesis and Functional Analysis†

    PubMed Central

    Pandini, Alessandro; Soshilov, Anatoly A.; Song, Yujuan; Zhao, Jing; Bonati, Laura; Denison, Michael S.

    2010-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent, basic helix–loop–helix Per-Arnt-Sim (PAS)-containing transcription factor that can bind and be activated by structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Our previous three-dimensional homology model of the mouse AhR (mAhR) PAS B ligand binding domain allowed identification of the binding site and its experimental validation. We have extended this analysis by conducting comparative structural modeling studies of the ligand binding domains of six additional high-affinity mammalian AhRs. These results, coupled with site-directed mutagenesis and AhR functional analysis, have allowed detection of the “TCDD binding-fingerprint” of conserved residues within the ligand binding cavity necessary for high-affinity TCDD binding and TCDD-dependent AhR transformation DNA binding. The essential role of selected residues was further evaluated using molecular docking simulations of TCDD with both wild-type and mutant mAhRs. Taken together, our results dramatically improve our understanding of the molecular determinants of TCDD binding and provide a basis for future studies directed toward rationalizing the observed species differences in AhR sensitivity to TCDD and understanding the mechanistic basis for the dramatic diversity in AhR ligand structure. PMID:19456125

  10. Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir.

    PubMed

    Hall, R J; Peacey, M P; Ralston, J C; Bocacao, J; Ziki, M; Gunn, W; Quirk, A; Huang, Q S

    2009-07-30

    New Zealand, like other southern hemisphere countries with a temperate climate, has been in the winter period with seasonal influenza activity. New Zealand has also experienced a dramatic increase in the number of cases of pandemic influenza A(H1N1)v virus. Early reports from the northern hemisphere at the beginning of the pandemic showed that the virus was sensitive to the antiviral drug oseltamivir. In this study we report that pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir, but seasonal influenza A(H1N1) viruses - the co-circulating predominant seasonal strain, is resistant to oseltamivir. PMID:19643060

  11. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

    The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10−7), rs4820294/rs2899292 (2.13 × 10−7) and rs62236673/rs2899292 (4.25 × 10−7) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10−7) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9). PMID:25687228

  14. 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.

  15. 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

  16. 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.

  17. [Advances in the structure and function of pandemic A/H1N1/2009 influenza virus HA protein].

    PubMed

    Zhang, Wen-Qiang; Song, Shao-Xia; Wang, Tong-Zhan

    2012-06-01

    Since March 2009, pandemic A/H1N1/2009 influenza virus has been spreading throughout many countries including China. The emerged virus caused great harm to human health and social economy. Hemagglutinin (HA) is the most important viral surface glycoprotein, mainly possessing three kinds of functions: (1) binding to host cell receptor, (2) triggering the fusion between viral envelop and target cell membrane, (3) stimulating the body to generate the neutralizing antibody. Advances in the structure, primary function, evolution and antigenicity of pandemic A/H1N1/2009 influenza virus HA protein are reviewed in this paper. PMID:22978172

  18. 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. PMID:26980671

  19. Aminoterminal amphipathic α-helix AH1 of hepatitis C virus nonstructural protein 4B possesses a dual role in RNA replication and virus production.

    PubMed

    Gouttenoire, Jérôme; Montserret, Roland; Paul, David; Castillo, Rosa; Meister, Simon; Bartenschlager, Ralf; Penin, François; Moradpour, Darius

    2014-10-01

    Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV) replication complex formation. In concert with other nonstructural proteins, it induces a specific membrane rearrangement, designated as membranous web, which serves as a scaffold for the HCV replicase. The N-terminal part of NS4B comprises a predicted and a structurally resolved amphipathic α-helix, designated as AH1 and AH2, respectively. Here, we report a detailed structure-function analysis of NS4B AH1. Circular dichroism and nuclear magnetic resonance structural analyses revealed that AH1 folds into an amphipathic α-helix extending from NS4B amino acid 4 to 32, with positively charged residues flanking the helix. These residues are conserved among hepaciviruses. Mutagenesis and selection of pseudorevertants revealed an important role of these residues in RNA replication by affecting the biogenesis of double-membrane vesicles making up the membranous web. Moreover, alanine substitution of conserved acidic residues on the hydrophilic side of the helix reduced infectivity without significantly affecting RNA replication, indicating that AH1 is also involved in virus production. Selective membrane permeabilization and immunofluorescence microscopy analyses of a functional replicon harboring an epitope tag between NS4B AH1 and AH2 revealed a dual membrane topology of the N-terminal part of NS4B during HCV RNA replication. Luminal translocation was unaffected by the mutations introduced into AH1, but was abrogated by mutations introduced into AH2. In conclusion, our study reports the three-dimensional structure of AH1 from HCV NS4B, and highlights the importance of positively charged amino acid residues flanking this amphipathic α-helix in membranous web formation and RNA replication. In addition, we demonstrate that AH1 possesses a dual role in RNA replication and virus production, potentially governed by different topologies of the N-terminal part of NS4B. PMID:25392992

  20. 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. PMID:24898420

  1. 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.

  2. Differential Glycosylation of Polar and Lateral Flagellins in Aeromonas hydrophila AH-3*

    PubMed Central

    Wilhelms, Markus; Fulton, Kelly M.; Twine, Susan M.; Tomás, Juan M.; Merino, Susana

    2012-01-01

    Polar and lateral flagellin proteins from Aeromonas hydrophila strain AH-3 (serotype O34) were found to be glycosylated with different carbohydrate moieties. The lateral flagellin was modified at three sites in O-linkage, with a single monosaccharide of 376 Da, which we show to be a pseudaminic acid derivative. The polar flagellin was modified with a heterogeneous glycan, comprised of a heptasaccharide, linked through the same 376-Da sugar to the protein backbone, also in O-linkage. In-frame deletion mutants of pseudaminic acid biosynthetic genes pseB and pseF homologues resulted in abolition of polar and lateral flagellar formation by posttranscriptional regulation of the flagellins, which was restored by complementation with wild type pseB or F homologues or Campylobacter pseB and F. PMID:22733809

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Multiple Myeloma and Glyphosate Use: A Re-Analysis of US Agricultural Health Study (AHS) Data

    PubMed Central

    Sorahan, Tom

    2015-01-01

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

  8. 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).

  9. Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine

    PubMed Central

    Deng, Yi‐Mo; Iannello, Pina; Smith, Ina; Watson, James; Barr, Ian G.; Daniels, Peter; Komadina, Naomi; Harrower, Bruce; Wong, Frank Y. K.

    2012-01-01

    Please cite this paper as: Deng et al. (2012). Transmission of influenza A(H1N1) 2009 pandemic viruses in Australian swine. Influenza and Other Respiratory Viruses 6(3), e42–e47. Background  Swine have receptors for both human and avian influenza viruses and are a natural host for influenza A viruses. The 2009 influenza A(H1N1) pandemic (H1N1pdm) virus that was derived from avian, human and swine influenza viruses has infected pigs in various countries. Objectives  To investigate the relationship between the H1N1pdm viruses isolated from piggery outbreaks in Australia and human samples associated with one of the outbreaks by phylogenetic analysis, and to determine whether there was any reassortment event occurring during the human‐pig interspecies transmission. Methods  Real‐time RT‐PCR and full genome sequencing were carried out on RNA isolated from nasal swabs and/or virus cultures. Phylogenetic analysis was performed using the Geneious package. Results  The influenza H1N1pdm outbreaks were detected in three pig farms located in three different states in Australia. Further analysis of the Queensland outbreak led to the identification of two distinct virus strains in the pigs. Two staff working in the same piggery were also infected with the same two strains found in the pigs. Full genome sequence analysis on the viruses isolated from pigs and humans did not identify any reassortment of these H1N1pdm viruses with seasonal or avian influenza A viruses. Conclusions  This is the first report of swine infected with influenza in Australia and marked the end of the influenza‐free era for the Australian swine industry. Although no reassortment was detected in these cases, the ability of these viruses to cross between pigs and humans highlights the importance of monitoring swine for novel influenza infections. PMID:22336333

  10. Swine flu. Mexico's handling of A/H1N1 in comparative perspective.

    PubMed

    Ear, Sophal

    2012-01-01

    Emerging infectious diseases (EIDs) pose international security threats because of their potential to inflict harm upon humans, crops, livestock, health infrastructure, and economies. Despite the scale of this threat, there are inherent limitations in preventing and controlling EIDs, including the scope of current disease surveillance efforts. All of this leads to the following questions in the context of Mexico's recent swine flu experience: What were the cultural, political, and economic challenges to Influenza A/H1N1 virus response in Mexico? By way of comparison, what can we learn from the U.S. experience in 1976 with A/New Jersey/76 (Hsw1N1), later referred to as H1N1? This article explores the comparative political economy of Mexico's handling of influenza virus A/H1N1 outbreak in 2009. Research provides notable observations-based on the strengths and weaknesses of each country's response--that can be used as a starting point of discussion for the design of effective EIDs surveillance programs in developing and middle-income countries. In the U.S., the speed and efficiency of the 1976 U.S. mobilization against H1N1 was laudable. Although the U.S. response to the outbreak is seldom praised, the unity of the scientific and political communities demonstrated the national ability to respond to the situation. Mexico's strongest characteristics were its transparency, as well as the cooperation the country exhibited with other nations, particularly the U.S. and Canada. While Mexico showed savvy in its effective management of public and media relations, as the article details, political, economic, and cultural problems persisted. PMID:23379315

  11. 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

  12. Preparation of genetically engineered A/H5N1 and A/H7N1 pandemic vaccine viruses by reverse genetics in a mixture of Vero and chicken embryo cells

    PubMed Central

    Legastelois, Isabelle; Garcia‐Sastre, Adolfo; Palese, Peter; Tumpey, Terrence M.; Maines, Taronna R.; Katz, Jacqueline M.; Vogel, Frederick R.; Moste, Catherine

    2007-01-01

    Background  In case of influenza pandemic, a robust, easy and clean technique to prepare reassortants would be necessary. Objectives  Using reverse genetics, we prepared two vaccine reassortants (A/H5N1 × PR8 and A/H7N1 × PR8) exhibiting the envelope glycoproteins from non‐pathogenic avian viruses, A/Turkey/Wisconsin/68 (A/H5N9) and A/Rhea/New Caledonia/39482/93 (A/H7N1) and the internal proteins of the attenuated human virus A/Puerto Rico/8/34 (H1N1). Methods  The transfection was accomplished using a mixture of Vero and chicken embryo cells both of which are currently being used for vaccine manufacturing. Results  This process was reproducible, resulting in consistent recovery of influenza viruses in 6 days. Because it is mainly the A/H5N1 strain that has recently crossed the human barrier, it is the A/PR8 × A/H5N1 reassortant (RG5) that was further amplified, either in embryonated hen eggs or Vero cells, to produce vaccine pre‐master seed stocks that met quality control specifications. Safety testing in chickens and ferrets was performed to assess the non‐virulence of the reassortant, and finally analysis using chicken and ferret sera immunized with the RG5 virus showed that the vaccine candidate elicited an antibody response cross‐reactive with the Hong Kong 1997 and 2003 H5N1 strains but not the Vietnam/2004 viruses. Conclusions  The seeds obtained could be used as part of a pandemic vaccine strain ‘library’ available in case of propagation in humans of a new highly pathogenic avian strain. PMID:19453414

  13. 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.

  14. 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

  15. 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

  16. Contact tracing for influenza A(H1N1)pdm09 virus-infected passenger on international flight.

    PubMed

    Shankar, Ananda G; Janmohamed, Kulsum; Olowokure, Babatunde; Smith, Gillian E; Hogan, Angela H; De Souza, Valerie; Wallensten, Anders; Oliver, Isabel; Blatchford, Oliver; Cleary, Paul; Ibbotson, Sue

    2014-01-01

    In April 2009, influenza A(H1N1)pdm09 virus infection was confirmed in a person who had been symptomatic while traveling on a commercial flight from Mexico to the United Kingdom. Retrospective public health investigation and contact tracing led to the identification of 8 additional confirmed cases among passengers and community contacts of passengers. PMID:24377724

  17. 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

  18. Use of National Pneumonia Surveillance to Describe Influenza A(H7N9) Virus Epidemiology, China, 2004–2013

    PubMed Central

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

    2013-01-01

    In mainland China, most avian influenza A(H7N9) cases in the spring of 2013 were reported through the pneumonia of unknown etiology (PUE) surveillance system. To understand the role of possible underreporting and surveillance bias in assessing the epidemiology of subtype H7N9 cases and the effect of live-poultry market closures, we examined all PUE cases reported from 2004 through May 3, 2013. Historically, the PUE system was underused, reporting was inconsistent, and PUE reporting was biased toward A(H7N9)-affected provinces, with sparse data from unaffected provinces; however, we found no evidence that the older ages of persons with A(H7N9) resulted from surveillance bias. The absolute number and the proportion of PUE cases confirmed to be A(H7N9) declined after live-poultry market closures (p<0.001), indicating that market closures might have positively affected outbreak control. In China, PUE surveillance needs to be improved. PMID:24206646

  19. Acute fibrinous and organizing pneumonia associated with influenza A/H1N1 pneumonia after lung transplantation

    PubMed Central

    2013-01-01

    Background Immunocompromised patients, particularly after lung transplantation, are at high risk to develop atypical forms of pulmonary infections including influenza A/H1N1. Acute Fibrinous and Organizing Pneumonia (AFOP) is a special histological pattern in acute respiratory failure with high mortality. Case presentation We describe a 66-year-old woman with double lung transplantation in August 2009 due to end stage pulmonary fibrosis. After prolonged weaning and subsequent promising course, she developed atypical pneumonia with diffuse pulmonary infiltrates in both lungs in January 2010. Infection with influenza A/H1N1 virus was verified. The patient rapidly suffered from respiratory insufficiency and died eight days after this diagnosis. The post-mortem revealed especially in the lower parts of the lungs the classical histological pattern of pure AFOP. Molecular analyses of lung tissue were positive for influenza A/H1N1. Conclusion To our knowledge we present the first case of AFOP triggered by viral infection, here proven to be influenza virus A/H1N1. Thus, also in the setting of viral infection the highly deadly differential diagnosis of AFOP must be considered. PMID:23683442

  20. AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity.

    PubMed

    Brantley, Eileen; Callero, Mariana A; Berardi, Damian E; Campbell, Petreena; Rowland, Leah; Zylstra, Dain; Amis, Louisa; Yee, Michael; Simian, Marina; Todaro, Laura; Loaiza-Perez, Andrea I; Soto, Ubaldo

    2016-06-28

    Traditional chemotherapies debulk tumors but fail to produce long-term clinical remissions due to their inability to eradicate tumor-initiating cells (TICs). This necessitates therapy with activity against the TIC niche. Αlpha6-integrin (α6-integrin) promotes TIC growth. In contrast, aryl hydrocarbon receptor (AhR) signaling activation impedes the formation of mammospheres (clusters of cells enriched for TICs). We investigated the ability of AhR agonist Aminoflavone (AF) and AF pro-drug (AFP464) to disrupt mammospheres derived from breast cancer cells and a M05 mammary mouse model of breast cancer respectively. We further examined the capacity of AF and AFP464 to exhibit anticancer activity and modulate the expression of 'stemness' genes including α6-integrin using immunofluorescence, flow cytometry and qRT-PCR analysis. AF disrupted mammospheres and prevented secondary mammosphere formation. In contrast, AF did not disrupt mammospheres derived from AhR ligand-unresponsive MCF-7 cells. AFP464 treatment suppressed M05 tumor growth and disrupted corresponding mammospheres. AF and AFP464 reduced the expression and percentage of cells that stained for 'stemness' markers including α6-integrin in vitro and in vivo respectively. These data suggest AFP464 thwarts bulk breast tumor and TIC growth via AhR agonist-mediated α6-integrin inhibition. PMID:26996297

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

    PubMed

    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

  2. Reassortant Avian Influenza A(H9N2) Viruses in Chickens in Retail Poultry Shops, Pakistan, 2009–2010

    PubMed Central

    Angot, Angélique; Rashid, Hamad B.; Cattoli, Giovanni; Hussain, Manzoor; Trovò, Giulia; Drago, Alessandra; Valastro, Viviana; Thrusfield, Michael; Welburn, Sue; Eisler, Mark C.; Capua, Ilaria

    2015-01-01

    Phylogenetic analysis of influenza viruses collected during December 2009–February 2010 from chickens in live poultry retail shops in Lahore, Pakistan, showed influenza A(H9N2) lineage polymerase and nonstructural genes generate through inter- and intrasubtypic reassortments. Many amino acid signatures observed were characteristic of human isolates; hence, their circulation could enhance inter- or intrasubtypic reassortment. PMID:25811830

  3. 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

  4. Seroprevalence of influenza A(H1N1)pdm09 virus antibody, England, 2010 and 2011.

    PubMed

    Hoschler, Katja; Thompson, Catherine; Andrews, Nick; Galiano, Monica; Pebody, Richard; Ellis, Joanna; Stanford, Elaine; Baguelin, Marc; Miller, Elizabeth; Zambon, Maria

    2012-11-01

    The intense influenza activity in England during the 2010-11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults. PMID:23092684

  5. Seroprevalence of Influenza A(H1N1)pdm09 Virus Antibody, England, 2010 and 2011

    PubMed Central

    Thompson, Catherine; Andrews, Nick; Galiano, Monica; Pebody, Richard; Ellis, Joanna; Stanford, Elaine; Baguelin, Marc; Miller, Elizabeth; Zambon, Maria

    2012-01-01

    The intense influenza activity in England during the 2010–11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults. PMID:23092684

  6. 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...

  7. BINDING OF POLYCHLORINATED BIPHENYLS CLASSIFIED AS EITHER PHENOBARBITONE-, 3-METHYLCHOLANTHRENE- OR MIXED-TYPE INDUCERS TO CYTOSOLIC AH RECEPTOR

    EPA Science Inventory

    It has been postulated that reversible, high-affinity binding of 3-methyl-cholanthrene (MC)-type inducers to a receptor protein (the Ah receptor) in hepatic cytosol is essential for induction of aryl hydrocarbon hydroxylase (AHH) enzymic activity. To test this postulate, the bind...

  8. 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

  9. 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

  10. Influenza A(H5N2) virus antibodies in humans after contact with infected poultry, Taiwan, 2012.

    PubMed

    Wu, Ho-Sheng; Yang, Ji-Rong; Liu, Ming-Tsan; Yang, Chin-Hui; Cheng, Ming-Chu; Chang, Feng-Yee

    2014-05-01

    Six persons in Taiwan who had contact with poultry infected with influenza A(H5N2) showed seroconversion for the virus by hemagglutinin inhibition or microneutralization testing. We developed an ELISA based on nonstructural protein 1 of the virus to differentiate natural infection from cross-reactivity after vaccination; 2 persons also showed seroconversion by this test. PMID:24750594

  11. SPATIOTEMPORAL TRENDS OF CASES OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN ARGENTINA, 2009-2012

    PubMed Central

    LEVEAU, Carlos M.; UEZ, Osvaldo; VACCHINO, Marta N.

    2015-01-01

    The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies. PMID:25923892

  12. Epidemiological aspects of pandemic influenza A(H1N1) virus from 2009 to 2011 in Iran

    PubMed Central

    Yavarian, Jila; Naseri, Maryam; Shadab, Azadeh; Shafiei Jandaghi, Nazanin Z.; Mokhtari Azad, Talat

    2012-01-01

    Please cite this paper as: Yavarian et al. (2012). Epidemiological aspects of pandemic influenza A(H1N1) virus from 2009 to 2011 in Iran. Influenza and Other Respiratory Viruses 6(601), e74–e76. PMID:22487173

  13. 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…

  14. 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

  15. Spatiotemporal trends of cases of pandemic influenza A(H1N1)pdm09 in Argentina, 2009-2012.

    PubMed

    Leveau, Carlos M; Uez, Osvaldo; Vacchino, Marta N

    2015-01-01

    The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies. PMID:25923892

  16. 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

  17. 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

  18. 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

  19. Targeted delivery of DNA using YEE(GalNAcAH)3, a synthetic glycopeptide ligand for the asialoglycoprotein receptor.

    PubMed

    Merwin, J R; Noell, G S; Thomas, W L; Chiou, H C; DeRome, M E; McKee, T D; Spitalny, G L; Findeis, M A

    1994-01-01

    In vivo gene therapy shows promise as a treatment for both genetic and acquired disorders. The hepatic asialoglycoprotein receptor (ASGPr) binds asialoorosomucoid-polylysine-DNA (ASOR-PL-DNA) complexes and allows targeted delivery to hepatocytes. The tris(N-acetylgalactosamine aminohexyl glycoside) amide of tyrosyl(glutamyl) glutamate [YEE(GalNAcAH)3] has been previously reported to have subnanomolar affinity for the ASGPr. We have used an iodinated derivative of YEE(GalNAcAH)3 linked to polylysine and complexed to the luciferase gene (pCMV-Luc) in receptor-binding experiments to establish the feasibility of substituting ASOR with the synthetic glycopeptide for gene therapy. Scatchard analyses revealed similar Kd values for both ASOR and the glycopeptide. Binding and internalization of 125I-Suc-YEE(GalNAcAH)3 were competitively inhibited with either unlabeled ASOR or glycopeptide. The reverse was also true; 125I-ASOR binding was competed with unlabeled YEE(GalNAcAH)3 suggesting specific binding to the ASGPr by both compounds. Examination of in vivo delivery revealed that the 125I-labeled glycopeptide complex mimicked previous results observed with 125I-ASOR-PL-DNA. CPM in the liver accounted for 96% of the radioactivity recovered from the five major organs (liver, spleen, kidney, heart, and lungs). Cryoautoradiography displayed iodinated glycopeptide complex bound preferentially to hepatocytes rather than nonparenchymal cells. In vitro, as well as in vivo, transfections using the glycopeptide-polylysine-pCMV-luciferase gene complex (YG3-PL-Luc) resulted in expression of the gene product. These data demonstrate that the YEE(GalNAcAH)3 synthetic glycopeptide can be used as a ligand in targeted delivery of DNA to the liver-specific ASGPr. PMID:7873664

  20. 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.

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

    PubMed

    Hov, Johannes R; Zhong, Huanzi; Qin, Bingcai; Anmarkrud, Jarl Andreas; Holm, Kristian; Franke, Andre; Lie, Benedicte A; Karlsen, Tom H

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

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

    PubMed

    Ghotbaddini, Maryam; Powell, Joann B

    2015-07-01

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

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

    PubMed Central

    Ghotbaddini, Maryam; Powell, Joann B.

    2015-01-01

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

  10. Deterioration estimation of lithium-ion cells in direct current power supply systems and characteristics of 400-Ah lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Matsushima, Toshio

    Our evaluation of various characteristics of large-capacity 40 Ah and 80 Ah Lithium-ion (Li-ion) cells developed for industrial use shows that these cells exhibit reduced voltage characteristics and increased internal resistance in degraded conditions. We constructed a DC power supply system for telecommunications equipment using 80 Ah Li-ion batteries incorporating a function to estimate the cell status from the voltage characteristics during an automatic discharge of the battery. The Li-ion batteries in this system are maintained by a floating charge method, and we miniaturized the battery unit. In a field trial test lasting approximately 2 years, this DC power supply system performed well inclusive of the automatic discharge. The specifications and characteristics of prototype 200 Ah and 400 Ah cells, which were assembled to expand the application areas of Li-ion cells, are shown. Because these cells have similar characteristics to those of current 40 Ah and 80 Ah cells, they can be widely used as a substitute for conventional valve-regulated lead-acid (VRLA) cells.

  11. 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

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

    NASA Astrophysics Data System (ADS)

    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.

    2011-01-01

    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.

  13. The early diversification of influenza A/H1N1pdm.

    PubMed

    Nelson, Martha; Spiro, David; Wentworth, David; Beck, Eric; Fan, Jiang; Ghedin, Elodie; Halpin, Rebecca; Bera, Jayati; Hine, Erin; Proudfoot, Kathleen; Stockwell, Tim; Lin, Xudong; Griesemer, Sara; Kumar, Swati; Bose, Michael; 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

  14. 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.

  15. Koningiopisins A-H, Polyketides with Synergistic Antifungal Activities from the Endophytic Fungus Trichoderma koningiopsis.

    PubMed

    Liu, Kai; Yang, Yabin; Miao, Cui-Ping; Zheng, You-Kun; Chen, Jin-Lian; Chen, You-Wei; Xu, Li-Hua; Guang, Hui-Lin; Ding, Zhong-Tao; Zhao, Li-Xing

    2016-03-01

    Eight new fungal polyketides named koningiopisins A-H (1-8) and four previously known polyketides (9-12) were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH 30002. Their structures were elucidated using extensive spectral data interpretation, and their antifungal and synergistic activities were also evaluated. Koningiopisin C (3) exhibited in vitro antifungal activity against the phytopathogenic fungus Plectosphaerella cucumerina with an MIC of 16 µg/mL. Although the antifungal activities of single compounds were not obvious, a mixture of six compounds (4-9) exhibited potent synergistic antifungal activity against P. cucumerina with an MIC of 16 µg/mL, and the antifungal activity of the mixture of any two compounds with a 1:1 ratio was better than that observed from the individual compound. The synergistic biological activity of the metabolites in YIM PH 30002 demonstrates the significant ecological function of the endophyte for its host plant, and provides additional insight into the search for and development of agents for biological control. PMID:26692458

  16. 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

  17. 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

  18. Evaluation of Cycle Life and Characterization of YTP 45 Ah Li-Ion Battery for EMU

    NASA Technical Reports Server (NTRS)

    Deng, Yi; Jeevarajan, Judith; Rehm, Raymond; Bragg, Bobby; Strangways, Brad

    2002-01-01

    Li-ion batteries, with longer cycle life and higher energy density features, are now more and more attractive and applied in multiple fields. The YTP 45 Ah Li-ion battery has been evaluated here and may be employed in EMU in the future. Evaluations were on: (1) Cycle life tests - 500 cycles total (completed 40 cycles in simulated shuttle use mode and 460 cycles in an accelerated use mode, and recorded differential voltage of individual cell in battery); (2) Characterization test - discharge capacity measurement in environment temperature of -10, 25, 50 C before and after 500 cycles; and (3) Thermal testing - charge and discharge at 50 C and -10 C before and after 500 cycles. The battery showed less than a 9% drop of initial discharge capacity and energy within 500 cycles with 475 cycles 59% DOD plus 25 cycles 100% DOD. The EOD voltage ranged from 16.0 to 18.0 V, which fits the requirement for operating the EMU.

  19. [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. PMID:26975112

  20. Characterization of 109 Ah Ni-MH batteries charging with hydrogen sensing termination

    NASA Astrophysics Data System (ADS)

    Viera, J. C.; González, M.; Liaw, B. Y.; Ferrero, F. J.; Álvarez, J. C.; Campo, J. C.; Blanco, C.

    The use of Ni-MH batteries for traction applications in electric and hybrid vehicles is increasingly attractive and reliable. Besides the energy and power handling, and the cost issues, high tolerance to abuse is an important aspect of the Ni-MH technology. Thus, the ability to reduce charging time and to absorb regenerative breaking is highly desirable in these traction applications. This requires an accurate control of the charge termination. To facilitate an easy and reliable charging control and to avoid battery premature failure or ageing it is very important to know the behavior of the battery under a range of charging conditions. In this paper, we described the performance of high capacity commercial Ni-MH traction batteries (12 V, 109 Ah modules) when subjected to different charging rates (0.1, 0.2, 0.5, and 1.0 C) from 100% depth of discharge (DOD). Changes in battery voltage and temperature during charging were monitored, with a particular emphasis on the detection of the presence of hydrogen near the battery. This unique hydrogen detection outside the battery was used as the method for the end-of-charge termination to prevent overcharging of the battery. Relevant parameters, such as charge acceptance, energy efficiency, and charging time, were analyzed for comparison.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Influenza A(H1N1)pdm09 during air travel.

    PubMed

    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

    2013-01-01

    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

  6. 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

  7. 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

  8. 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

  9. Dual resistance to adamantanes and oseltamivir among seasonal influenza A(H1N1) viruses: 2008-2010.

    PubMed

    Sheu, Tiffany G; Fry, Alicia M; Garten, Rebecca J; Deyde, Varough M; Shwe, Thein; Bullion, Lesley; Peebles, Patrick J; Li, Yan; Klimov, Alexander I; Gubareva, Larisa V

    2011-01-01

    Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored. PMID:21148491

  10. Dual Resistance to Adamantanes and Oseltamivir Among Seasonal Influenza A(H1N1) Viruses: 2008–2010

    PubMed Central

    Sheu, Tiffany G.; Fry, Alicia M.; Garten, Rebecca J.; Deyde, Varough M.; Shwe, Thein; Bullion, Lesley; Peebles, Patrick J.; Li, Yan; Klimov, Alexander I.

    2011-01-01

    Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored. PMID:21148491

  11. Possible Role of Songbirds and Parakeets in Transmission of Influenza A(H7N9) Virus to Humans

    PubMed Central

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

    2014-01-01

    Avian-origin influenza A(H7N9) recently emerged in China, causing severe human disease. Several subtype H7N9 isolates contain influenza genes previously identified in viruses from finch-like birds. Because wild and domestic songbirds interact with humans and poultry, we investigated the susceptibility and transmissibility of subtype H7N9 in these species. Finches, sparrows, and parakeets supported replication of a human subtype H7N9 isolate, shed high titers through the oropharyngeal route, and showed few disease signs. Virus was shed into water troughs, and several contact animals seroconverted, although they shed little virus. Our study demonstrates that a human isolate can replicate in and be shed by such songbirds and parakeets into their environment. This finding has implications for these birds’ potential as intermediate hosts with the ability to facilitate transmission and dissemination of A(H7N9) virus. PMID:24572739

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

    PubMed

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

    2014-03-01

    Avian-origin influenza A(H7N9) recently emerged in China, causing severe human disease. Several subtype H7N9 isolates contain influenza genes previously identified in viruses from finch-like birds. Because wild and domestic songbirds interact with humans and poultry, we investigated the susceptibility and transmissibility of subtype H7N9 in these species. Finches, sparrows, and parakeets supported replication of a human subtype H7N9 isolate, shed high titers through the oropharyngeal route, and showed few disease signs. Virus was shed into water troughs, and several contact animals seroconverted, although they shed little virus. Our study demonstrates that a human isolate can replicate in and be shed by such songbirds and parakeets into their environment. This finding has implications for these birds' potential as intermediate hosts with the ability to facilitate transmission and dissemination of A(H7N9) virus. PMID:24572739

  13. Field Trial on a Rack-mounted DC Power Supply System with 80-Ah Lithium-ion Batteries

    NASA Astrophysics Data System (ADS)

    Matsushima, Toshio

    Using an industrial lithium-ion battery that has higher energy density than conventional valve-regulated lead-acid batteries, a rack-mounted DC-power-supply system was assembled and tested at a base transceiver station (BTS) offering actual services. A nominal output voltage and maximum output current of the system is 53.5V and 20A, respectively. An 80-Ah lithium-ion battery composed of 13 cells connected in series was applied in the system and maintained in a floating charge method. The DC-power-supply system was installed in a 19-inch power rack in the telecommunications equipment box at BTS. The characteristics of the 80Ah lithium-ion battery, specifications of the DC-power-supply system and field-test results were shown in this paper.

  14. Natural A(H1N1)pdm09 influenza virus infection case in a pet ferret in Taiwan.

    PubMed

    Lin, Hui-Ting; Wang, Ching-Ho; Wu, Wen-Ling; Chi, Chau-Hwa; Wang, Lih Chiann

    2014-11-01

    Ferrets have demonstrated high susceptibility to the influenza virus. This study discusses a natural 2009 pandemic influenza A (H1N1) (A(H1N1)pdm09) virus infection in a pet ferret (Mustela putorius furo) identified in Taiwan in 2013. The ferret was in close contact with family members who had recently experienced an influenza-like illness (ILI). The ferret nasal swab showed positive results for influenza A virus using one-step RT-PCR. The virus was isolated and the phylogenetic analysis indicated that all of the eight segmented genes were closely related to the human A(H1N1)pdm09 virus linage isolated in Taiwan. This study may provide a perspective view on natural influenza A virus transmission from the local human population into pet ferrets. PMID:25597188

  15. Full Genome Analysis of Influenza A(H1N1)pdm09 Virus Isolated from Peru, 2013.

    PubMed

    Padilla, Carlos; Condori, Fredy; Huaringa, Maribel; Marcos, Pool; Rojas, Nancy; Gutierrez, Victoria; Cáceres, Omar

    2014-01-01

    The pandemic influenza A(H1N1)pdm09 virus has been reported in Peru since 2009. We report the whole-genome sequence analysis of a viral isolate from an infection case that occurred during an influenza outbreak in 2013. This strain shows novel hemagglutinin (HA) mutations that may cause an antigenic drift that diminishes the protective effect of the vaccine. PMID:24744325

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

    PubMed

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

    2009-09-10

    Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT-PCR for influenza A(H1N1)v virus was set up ad hoc and validated following industry-standard criteria. The lower limit of detection of the assay was 384 copies of viral RNA per ml of viral transport medium (95% confidence interval: 273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference samples including seasonal human influenza A virus H1N1 and H3N2, highly pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2 and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene recommended in 2007 by the World Health Organization was modified to work under the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both assays were equally sensitive. Clinical applicability of both assays was demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens, which included samples from the first cases of pandemic H1N1 influenza imported to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory-confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology proved its principle and might assist public health laboratories in the upcoming influenza pandemic. PMID:19758541

  17. Determination of parameters of W UMa-type systems - V757 Cen, GW Cep, BX Peg, AH VIR

    NASA Astrophysics Data System (ADS)

    Kaluzny, J.

    Photoelectric light curves of four W UMa-type systems (V757 Cen, GW Cep, BX Peg, AH Vir) have been solved using the Ruciński code. The solutions were obtained for two assumed values of the gravity darkening exponent (β = 0.00 and β = 0.08). It is concluded that it is hard to distinguish between those two values basing on the wide band photometry in the visual wavelength domain.

  18. 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

  19. 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

  20. Relationship between murine Ah phenotype and the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD)

    SciTech Connect

    Shen, E.S.; Olson, J.R.

    1986-03-05

    The Ah receptor has been correlated with the toxic effects of TCDD in C57BL/6J (B6) and DBA/2J (D2) mice. The B6 strain, which has a high affinity cytosolic Ah receptor, is more sensitive to TCDD than the D2 strain, which lacks this receptor. The metabolism of TCDD was studied by incubating /sup 14/C-TCDD (2.2 ..mu..M) with hepatocytes from control and TCDD-pretreated B6 and D2 mice. Mice were pretreated with TCDD at doses that maximally induce ethoxyresorufin-O-deethylase (EROD) activity, a measure of Ah locus responsiveness to TCDD (B6, 3..mu..g/kg, ip;D2, 30..mu..g/kg, ip). Similar cytochrome P-450 content was detected in control B6 and D2 hepatocytes, however, TCDD pretreatment increased P-450 content 400% in B6 and 300% in D2 mice. No difference in hepatic EROD activity was found between control B6 and D2 mice (81.7 and 101.7 pmol/min/nmol P-450, respectively), but EROD activity was increased 17-fold in B6 and 10-fold in D2 mice after TCDD administration. The average rate of hepatic TCDD metabolism over two hours was similar in control B6 and D2 mice (1.103 and 0.945 pmol/hr/mg cell protein, respectively), although some qualitative differences in the metabolites were detected by HPLC. TCDD pretreatment produced no quantitative or qualitative changes in TCDD metabolism. These results suggest that the rate of hepatic TCDD metabolism does not correlate with genetic differences at the Ah locus.

  1. 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

  2. Role of endocrine disrupting chemicals in the occurrence of benign uterine leiomyomata: special emphasis on AhR tissue levels.

    PubMed

    Bidgoli, Sepideh Arbabi; Khorasani, Hoda; Keihan, Heideh; Sadeghipour, Alireza; Mehdizadeh, Abolfazl

    2012-01-01

    Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors. PMID:23317198

  3. 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

  4. Seropositivity for Influenza A(H1N1)pdm09 Virus among Frontline Health Care Personnel

    PubMed Central

    Alagappan, Kumar; Hancock, Kathy; Ward, Mary Frances; Akerman, Meredith; Dawood, Fatimah S.; Branch, Alicia; De Cicco, Sandra; Steward-Clark, Evelene; McCullough, Megan; Tenner, Karen; Katz, Jacqueline M.

    2013-01-01

    Seroprevalence of antibodies to influenza A(H1N1)pdm09 virus among 193 emergency department health care personnel was similar among 147 non–health care personnel (odds ratio 1.4, 95% CI 0.8–2.4). Working in an acute care setting did not substantially increase risk for virus infection above risk conferred by community-based exposures. PMID:23260627

  5. 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.

  6. 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.

  7. 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.

  8. Interactions among Ah receptor agonists in a novel human bioassay for induction of cytochrome P-450 IA1

    SciTech Connect

    Hasspieler, B.M.; Gillan, K.; Haffner, G.D.; Adeli, K.; Niimi, A.

    1995-12-31

    A widespread technique for monitoring pollutant exposure and toxicity is based upon induction of the cytochrome P450 (CYP) enzyme system. Numerous classes of xenobiotics, including PCBs, PAHs, PCDDs and PCDFs, stimulate induction of the CYP IA1 subfamily via binding to the intracellular Ah receptor. A widely-used catalytic marker for this subfamily is ethoxyresorufin 0-deethylase (EROD). Toxic equivalency factors may be calculated for ranking toxicity of pollutants relative to agonists such as 2,3,7,8,-TCDD, a highly potent inducer and Ah receptor ligand. These methods typically utilize cell lines from rodents (e.g., H4IIE) or fish (e.g., RTL 149), and although such models may be relevant to these and related species, they are of little direct applicability to human health concerns. The laboratory has recently developed a system for monitoring EROD induction in the HepG2 human hepatoma cell line. Treatment of HepG2 cells with Ah receptor agonists such as TCDD elicits induction responses, comparable to those observed in non-human bioassays. When cells are exposed to TCDD and purified PCBs simultaneously, significant interactions are observed. Both inductive and non-inductive PCB congeners appear to inhibit TCDD-mediated EROD induction, presumably due to competition for the Ah receptor ligand-binding site. This may potentially lead to gross underestimation of the toxicity of complex mixtures in which such interactions take place. Results demonstrate the utility of this novel bioassay for assessing hazard of environmental pollutant mixtures to human as well as ecosystem health.

  9. 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. PMID:26534871

  10. 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

  11. 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

  12. Vertical distribution of AhR-activating compounds in sediments contaminated by modernized pulp and paper industry.

    PubMed

    Ratia, H; Oikari, A

    2014-03-01

    Increased ethoxyresorufin-O-deethylase (EROD) activity is a sensitive biomarker of exposure to the chemicals which activate the aryl hydrocarbon receptor (AhR) and induce the cytochrome P450 system, such as many polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs). Pulp bleaching was one of the main sources of PCDDs and PCDFs until elemental chlorine free (ECF) and total chlorine free bleaching processes since 1990s have remarkably decreased but not completely eliminate discharges of these chemicals. In addition, historically contaminated sediments may act as a source of these persistent contaminants. In this study, the contamination history and recovery of a watercourse heavily loaded by the chemical wood industry were studied by analyzing PCDDs, PCDFs and PCBs from vertical sediment samples and by measuring hepatic EROD activity from rainbow trout intraperitoneally dosed with the sediment extracts. No PCDDs or PCDFs were found above the chromatographic limit of detection from the study area and only small amounts of PCB congeners 101, 138, 153, and 180 were present. No increased EROD activity was observed in fish indicating the absence of any AhR-activating compounds in the surface sediment, to about 15 cm depth, representing about the last 20 years when kraft pulping and ECF bleaching with activated wastewater treatment have been used. It can be concluded that nowadays organochlorines and other AhR-ligands do not harm the previously heavily polluted watercourse. PMID:24361517

  13. 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

  14. 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

  15. [Pandemic influenza A/H1N1v--guidelines for infection control from the perspective of Polish ITUs].

    PubMed

    Becler, Robert; Andruszkiewicz, Paweł; Kański, Andrzej

    2010-01-01

    In some countries, the influenza A/H1N1v pandemic, recently announced by WHO, was severe. Up to 10-30% of patients required ITU therapy due to rapidly increasing respiratory failure. In Poland, recommendations concerning the management of A/H1N1v infections, including those during ITU hospitalization, are vague and scattered. The WHO guidelines stress that the spread of infections should be limited by observance of personal hygiene rules, use of appropriate preventive measures and suitable administrative and technical actions. Only 30-60% of medical staff cleans their hands. Hand washing practices are inaccurate and too rare. Likewise, protective clothes and face masks are worn too rarely. FFP3 is believed to be the best mask in such cases, if properly used. Such masks should be individually adjusted, placed tightly over the face, without leaks around the edges. After use, masks and protective clothes should be considered as medical waste. Moreover, the guidelines for management of ITU patients diagnosed with A/H1N1v infections are extremely relevant in cases of other infections. PMID:20608215

  16. 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

  17. Bt proteins Cry1Ah and Cry2Ab do not affect cotton aphid Aphis gossypii and ladybeetle Propylea japonica.

    PubMed

    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

  18. Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin

    PubMed Central

    Ni, Fengyun; Kondrashkina, Elena; Wang, Qinghua

    2015-01-01

    In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA1 Q226, the triad of HA1 S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA1 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA1 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance. PMID:26226046

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

    PubMed Central

    Williams, Stephanie; Merianos, Angela; Mounts, Anthony

    2014-01-01

    Abstract 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. PMID:24391301

  20. 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

  1. Theoretical studies on the susceptibility of oseltamivir against variants of 2009 A/H1N1 influenza neuraminidase.

    PubMed

    Li, Lin; Li, Youyong; Zhang, Liling; Hou, Tingjun

    2012-10-22

    The outbreak and high speed global spread of the new strain of influenza A/H1N1 virus in 2009 posed a serious threat to global health. It is more likely that drug-resistant influenza strains will arise after the extensive use of anti-influenza drugs. Consequently, the identification of the potential resistant sites for drugs in advance and the understanding of the corresponding molecular mechanisms that cause drug resistance are quite important in the design of new drug candidates with better potency to combat drug resistance. Here, we performed molecular simulations to evaluate the potency of oseltamivir to combat drug resistance caused by the mutations in 2009 A/H1N1 neuraminidase (NA). We examined three representative drug-resistant mutations in NA, consisting of H274Y, N294S, and Y252H. First, a theoretical structure of A/H1N1 NA in complex with oseltamivir was constructed using homology modeling. Then, molecular dynamics (MD) simulations, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations, and MM/GBSA free energy decomposition were used to characterize the binding of oseltamivir with the wild type (WT) and three mutated NAs. Our predictions show that N294S and H274Y, two popular drug-resistant mutations in different variants of NA, still cause significant resistance to oseltamivir. However, the Y252H mutation does not impair the interactions between oseltamivir and A/H1N1 NA. An examination of individual energy components shows that the loss of polar interactions is the key source for the resistance of the studied mutations to oseltamivir. Moreover, free energy decomposition analysis and structural analysis reveal that the N294S or H274Y mutation triggers the large-scale conformational changes of the binding pocket and then impairs the affinity of oseltamivir. We expect that our results will be useful for the rational design of NA inhibitors with high potency against drug-resistant A/H1N1 mutants. PMID:22998323

  2. Deep, Low Mass Ratio Overcontact Binary Systems. VI. AH Cancri in the Old Open Cluster M67

    NASA Astrophysics Data System (ADS)

    Qian, S.-B.; Liu, L.; Soonthornthum, B.; Zhu, L.-Y.; He, J.-J.

    2006-06-01

    CCD photometric light curves in the B and V bands obtained in 2001 and in the V band obtained in 2002 of AH Cnc in the old open cluster M67 are presented. It is shown that AH Cnc is a total-eclipsing binary and its light curves correspond to a typical A type according to Binnendijk's classification. The variations of the light curve around the primary minimum and second maximum were found. Our nine epochs of light minimum monitored from 2001 to 2005, including others collected from the literature, were used to create the first study of the period changes of the binary system. A cyclic oscillation with a period of 36.5 yr and an amplitude of 0.0237 days was discovered to be superposed on a continuous period increase (dP/dt=3.99×10-7 days yr-1). Weak evidence indicates that there exists another small-amplitude period oscillation (A4=0.0035 days, P4=7.75 yr). The symmetric light curves in the B and V bands obtained in 2001 were analyzed with the 2003 version of the Wilson-Devinney code. It is confirmed that AH Cnc is a deep overcontact binary system with a high degree of overcontact f=58.5%+/-4.5% and a low mass ratio of q=0.1682+/-0.0012. The existence of the third light and the cyclic period oscillation both may suggest that AH Cnc is a triple system containing an unseen third body. The tertiary component may have played an important role in the origin of the overcontact binary star by removing angular momentum from the central system, which would cause it to have a short initial orbital period and thus evolve into an overcontact configuration by angular momentum loss. The long-term period increase can be interpreted as a mass transfer from the less massive component to the more massive one. As the orbital period increases, the decrease of the mass ratio will cause it finally to evolve into a single rapid-rotating star when the system meets the more familiar criterion that the orbital angular momentum be less than 3 times the total spin angular momentum. Therefore

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  5. 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. PMID:26037956

  6. 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.

  7. Plan, execute, and discuss vibration measurements and correlations to evaluate a NASTRAN finite element model of the AH-64 helicopter airframe

    NASA Technical Reports Server (NTRS)

    Ferg, D.; Foote, L.; Korkosz, G.; Straub, F.; Toossi, M.; Weisenburger, R.

    1990-01-01

    A ground vibration test was performed on the AH-64 (Apache) helicopter to determine the frequency response of the airframe. The structure was excited at both the main and tail rotor hubs, separately, and response measurements were taken at 102 locations throughout the fuselage structure. Frequency responses were compared and correlated with results from a NASTRAN finite element model of AH-64. In addition, natural frequencies and mode shapes were estimated from the frequency response data and were correlated with analytical results.

  8. 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

  9. 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

  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. Comparative in vitro transformation of the aromatic hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC)

    SciTech Connect

    Riddick, D.S.; Harper, P.A.; Okey, A.B.; Riddick, D.S. )

    1992-02-26

    The induction of CYP1A1 by halogenated (e.g. TCDD) and nonhalogenated (e.g. MC) aromatic hydrocarbons is mediated by the AhR. In cytosol prepared from the mouse hepatoma cell line Hepa-1, AhR bound TCDD with 3 to 4-fold greater affinity than MC, whereas TCDD was 960-fold more potent than MC as an inducer of aryl hydrocarbon hydroxylase (AHH) activity in cultured Hepa-1 cells. The objective of this study was to compare the potency and efficacy of TCDD and MC with respect to transformation of the cytosolic AhR to its DNA-binding form. Following incubation of Hepa-1 cytosol with TCDD or MC at 30 C for 4 h, the extent of AhR transformation was assessed by measuring interaction of the AhR-ligand complex with a {sup 32}P-labeled 26-bp oligonucleotide containing a single dioxin-responsive element (DRE) consensus sequence in a gel retardation assay. Concentration-response studies indicated that TCDD and MC did not differ significantly in AhR transformation potency, but MC displayed only about 70% of the efficacy of TCDD. In vitro transformation efficacy appears to be a determinant of AHH induction efficacy, but the small difference between TCDD and MC in transformation potency does not seem adequate to explain quantitatively the large difference in AHH induction potency displayed by these ligands.

  12. 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

  13. Interactions Between Estrogen- and Ah-Receptor Signalling Pathways in Primary Culture of Salmon Hepatocytes Exposed to Nonylphenol and 3,3',4,4'-Tetrachlorobiphenyl (Congener 77)

    PubMed Central

    Mortensen, Anne S; Arukwe, Augustine

    2007-01-01

    Background The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) and aryl hydrocarbon receptor (AhR), probably involving all subtypes and other co-factors. The anti-estrogenic activities of AhR agonists have been reported. In teleost fish, exposure to AhR agonists has been associated with reduced Vtg synthesis or impaired gonadal development in both in vivo- and in vitro studies. Inhibitory AhR and ER cross-talk have also been demonstrated in breast cancer cells, rodent uterus and mammary tumors. Previous studies have shown that AhR-agonists potentiate xenoestrogen-induced responses in fish in vivo system. Recently, several studies have shown that AhR-agonists directly activate ERα and induce estrogenic responses in mammalian in vitro systems. In this study, two separate experiments were performed to study the molecular interactions between ER and AhR signalling pathways using different concentration of PCB-77 (an AhR-agonist) and time factor, respectively. Firstly, primary Atlantic salmon hepatocytes were exposed to nonylphenol (NP: 5 μM – an ER agonist) singly or in combination with 0.001, 0.01 and 1 μM PCB-77 and sampled at 48 h post-exposure. Secondly, hepatocytes were exposed to NP (5 μM) or PCB-77 (1 μM) singly or in combination for 12, 24, 48 and 72 h. Samples were analyzed using a validated real-time PCR for genes in the ER pathway or known to be NP-responsive and AhR pathway or known to be PCB-77 responsive. Results Our data showed a reciprocal inhibitory interaction between NP and PCB-77. PCB-77 produced anti-NP-mediated effect by decreasing the mRNA expression of ER-responsive genes. NP produced anti-AhR mediated effect or as inhibitor of AhRα, AhRR, ARNT, CYP1A1 and UDPGT expression. A novel aspect of the present study is that low (0.001 μM) and medium (0.01 μM) PCB-77 concentrations increased ERα mRNA expression above

  14. Dentin wettability enhancement for three irrigating solutions and their effect on push out bond strength of gutta percha / AH Plus

    PubMed Central

    El Gendy, Abeer-Abdel-Hakim; El Ashry, Salma-Hassan

    2015-01-01

    Background The aim of this study was to investigate the effect of wettability enhancement for 17% EDTA, 2.5% sodium hypochlorite and 7% maleic acid solutions on push out bond strength of gutta percha /AH Plus to root dentin. Material and Methods One hundred and eight extracted single rooted human lower premolars were instrumented up to Protaper Universal F5 then irrigated with 3ml of 2.5% NaOCl after each file. Irrigants were prepared and a pilot study for determination of Tween 80 concentration yielding the lowest surface tension value in every solution was conducted. Samples were randomly divided into a control group and two experimental groups (17% EDTA and 7% Maleate), further split into eight subgroups (n=12), according to Tween 80 implementation sequence. Roots were obturated using gutta percha and AH plus by lateral condensation. Bond strength was measured by push out test. Mode of failure was then evaluated quantitatively by stereomicroscopy. Data were statistically analyzed using one way ANOVA followed by Tukey-Kramer for multiple comparisons. Results Control group showed the lowest values. Maleic acid subgroups showed significantly higher overall values than EDTA subgroups (P<0.05). Protocols implementing surfactant containing NaOCl showed significantly lower values than plain counterparts. Failure pattern was predominantly cohesive for plain regimens and the ones implementing Tween 80 in maleic acid solutions with plain NaOCl. Conclusions Tween 80 addition to demineralizing irrigants increased the bond strength values. Surfactant containing NaOCl solutions yielded lower bond strength than plain ones. Key words:Wettability enhancement for three irrigants vs. corresponding gutta percha/AH Plus bonding. PMID:26155339

  15. The atmospheric structure and fundamental parameters of the red supergiants AH Sco, UY Sct, and KW Sgr

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    We present the atmospheric structure and the fundamental parameters of the Red Supergiants (RSGs) AH Sco, UY Sct, and KW Sgr. We have carried out spectro-interferometric observations in the near-infrared bands (between 1.9 μm and 2.5 μm) with the VLTI/AMBER instrument in medium resolution. In the visibility data, we detect the presence of molecular layers of water and CO in extended atmospheres. For a uniform disk modelling, we observe size increases in the water band centered at 1.9 μm and in the CO band at 2.3--2.5 μm, with respect to the near-continuun bandpass (2.20-2.25 μm). Our near-infrared spectra of AH Sco, UY Sct, and KW Sgr are well reproduced by the PHOENIX model. However the synthetic visibility amplitudes of the model do not predict the large extensions of the molecular bands. The continuum (2.15-2.25 μm) appears free from contamination by molecular layers. Thus, the continuum fitting to the PHOENIX can be used to estimate the diameter. We estimate the Rosseland-mean photospheric angular diameter of AH Sco, UY Sct, and KW Sgr to be 6.12±0.7 mas, 5.67± 0.55 mas, and 4.07±0.65 mas, respectively (preliminary values). We estimate radii and effective temperatures, and place the stars in the HR diagram.

  16. Evolutionary dynamics of highly pathogenic avian influenza A/H5N1 HA clades and vaccine implementation in Vietnam

    PubMed Central

    Nguyen, Nga Thi Bich

    2014-01-01

    Based on hemagglutinin (HA) and neuraminidase (NA), influenza A virus is divided into 18 different HA (H1 to H18) and 11 NA types (N1 to N11), opening the possibility for reassortment between the HA and NA genes to generate new HxNy subtypes (where x could be any HA and y is any NA, possibly). In recent four years, since 2010, highly pathogenic avian influenza (HPAI) viruses of H5N1 subtype (HPAI A/H5N1) have become highly enzootic and dynamically evolved to form multiple H5 HA clades, particularly in China, Vietnam, Indonesia, Egypt, Cambodia, and Bangladesh. So far, after more than 10 years emerged in Vietnam (since late 2003), HPAI A/H5N1 is still posing a potential risk of causing outbreaks in poultry, with high frequency of annual endemics. Intragenic variation (referred to as antigenic drift) in HA (e.g., H5) has given rise to form numerous clades, typically marking the major timelines of the evolutionary status and vaccine application in each period. The dominance of genetically and antigenically diversified clade 2.3.2.1 (of subgroups a, b, c), clade 1.1 (1.1.1/1.1.2) and re-emergence of clade 7.1/7.2 at present, has urged Vietnam to the need for dynamically applied antigenicity-matching vaccines, i.e., the plan of importing Re-6 vaccine for use in 2014, in parallel use of Re-1/Re-5 since 2006. In this review, we summarize evolutionary features of HPAI A/H5N1 viruses and clade formation during recent 10 years (2004-2014). Dynamic of vaccine implementation in Vienam is also remarked. PMID:25003084

  17. Pandemic influenza A(H1N1)pdm09: risk of infection in primary healthcare workers

    PubMed Central

    Hudson, Ben; Toop, Les; Mangin, Dee; Brunton, Cheryl; Jennings, Lance; Fletcher, Lynn

    2013-01-01

    Background Healthcare workers in primary care are at risk of infection during an influenza pandemic. The 2009 influenza pandemic provided an opportunity to assess this risk. Aim To measure the prevalence of seropositivity to influenza A(H1N1)pdm09 among primary healthcare workers in Canterbury, New Zealand, following the 2009 influenza pandemic, and to examine associations between seropositivity and participants’ sociodemographic characteristics, professional roles, work patterns, and seasonal influenza vaccination status. Design and setting An observational study involving a questionnaire and testing for influenza A(H1N1)pdm09 seropositivity in all primary healthcare workers in Canterbury, New Zealand between December 2009 and February 2010. Method Participants completed a questionnaire that recorded sociodemographic and professional data, symptoms of influenza-like illness, history of seasonal influenza vaccination, and work patterns. Serum samples were collected and haemagglutination inhibition antibody titres to influenza A(H1N1)pdm09 measured. Results Questionnaires and serum samples were received from 1027 participants, from a workforce of 1476 (response rate 70%). Seropositivity was detected in 224 participants (22%). Receipt of seasonal influenza vaccine (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.2 to 3.3), recall of influenza (OR = 1.9, 95% CI = 1.3 to 2.8), and age ≤45 years (OR = 1.4, 95% CI = 1.0 to 1.9) were associated with seropositivity. Conclusion A total of 22% of primary care healthcare workers were seropositive. Younger participants, those who recalled having influenza, and those who had been vaccinated against seasonal influenza were more likely to be seropositive. Working in a dedicated influenza centre was not associated with an increased risk of seropositivity. PMID:23735413

  18. Transmission of Novel Influenza A(H1N1) in Households with Post-Exposure Antiviral Prophylaxis

    PubMed Central

    van Boven, Michiel; Donker, Tjibbe; van der Lubben, Mariken; van Gageldonk-Lafeber, Rianne B.; te Beest, Dennis E.; Koopmans, Marion; Meijer, Adam; Timen, Aura; Swaan, Corien; Dalhuijsen, Anton; Hahné, Susan; van den Hoek, Anneke; Teunis, Peter; van der Sande, Marianne A. B.; Wallinga, Jacco

    2010-01-01

    Background Despite impressive advances in our understanding of the biology of novel influenza A(H1N1) virus, little is as yet known about its transmission efficiency in close contact places such as households, schools, and workplaces. These are widely believed to be key in supporting propagating spread, and it is therefore of importance to assess the transmission levels of the virus in such settings. Methodology/Principal Findings We estimate the transmissibility of novel influenza A(H1N1) in 47 households in the Netherlands using stochastic epidemic models. All households contained a laboratory confirmed index case, and antiviral drugs (oseltamivir) were given to both the index case and other households members within 24 hours after detection of the index case. Among the 109 household contacts there were 9 secondary infections in 7 households. The overall estimated secondary attack rate is low (0.075, 95%CI: 0.037–0.13). There is statistical evidence indicating that older persons are less susceptible to infection than younger persons (relative susceptibility of older persons: 0.11, 95%CI: 0.024–0.43. Notably, the secondary attack rate from an older to a younger person is 0.35 (95%CI: 0.14–0.61) when using an age classification of ≤12 versus >12 years, and 0.28 (95%CI: 0.12–0.50) when using an age classification of ≤18 versus >18 years. Conclusions/Significance Our results indicate that the overall household transmission levels of novel influenza A(H1N1) in antiviral-treated households were low in the early stage of the epidemic. The relatively high rate of adult-to-child transmission indicates that control measures focused on this transmission route will be most effective in minimizing the total number of infections. PMID:20628642

  19. Top leads for swine influenza A/H1N1 virus revealed by steered molecular dynamics approach.

    PubMed

    Mai, Binh Khanh; Viet, Man Hoang; Li, Mai Suan

    2010-12-27

    Since March 2009, the rapid spread of infection during the recent A/H1N1 swine flu pandemic has raised concerns of a far more dangerous outcome should this virus become resistant to current drug therapies. Currently oseltamivir (tamiflu) is intensively used for the treatment of influenza and is reported effective for 2009 A/H1N1 virus. However, as this virus is evolving fast, some drug-resistant strains are emerging. Therefore, it is critical to seek alternative treatments and identify roots of the drug resistance. In this paper, we use the steered molecular dynamics (SMD) approach to estimate the binding affinity of ligands to the glycoprotein neuraminidase. Our idea is based on the hypothesis that the larger is the force needed to unbind a ligand from a receptor the higher its binding affinity. Using all-atom models with Gromos force field 43a1 and explicit water, we have studied the binding ability of 32 ligands to glycoprotein neuraminidase from swine flu virus A/H1N1. The electrostatic interaction is shown to play a more important role in binding affinity than the van der Waals one. We have found that four ligands 141562, 5069, 46080, and 117079 from the NSC set are the most promising candidates to cope with this virus, while peramivir, oseltamivir, and zanamivir are ranked 8, 11, and 20. The observation that these four ligands are better than existing commercial drugs has been also confirmed by our results on the binding free energies obtained by the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method. Our prediction may be useful for the therapeutic application. PMID:21090736

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Heparin-binding protein (HBP) in critically ill patients with influenza A(H1N1) infection.

    PubMed

    Kaukonen, K-M; Linko, R; Herwald, H; Lindbom, L; Ruokonen, E; Ala-Kokko, T; Pettilä, V

    2013-12-01

    Heparin-binding protein (HBP) is an inducer of vascular endothelial leakage in severe infections. Fluid accumulation into alveoli is a general finding in acute respiratory distress syndrome (ARDS). Severe acute respiratory failure with ARDS is a complication of influenza A(H1N1) infection. Accordingly, we studied the HBP levels in critically ill patients with infection of influenza A(H1N1).Critically ill patients in four intensive care units (ICUs) with polymerase chain reaction (PCR) confirmed infection of influenza A(H1N1) were prospectively evaluated. We collected clinical data and blood samples at ICU admission and on day 2. Twenty-nine patients participated in the study. Compared with normal plasma levels, the HBP concentrations were highly elevated at baseline and at day 2: 98 ng/mL (62-183 ng/mL) and 93 ng/mL (62-271 ng/mL) (p 0.876), respectively. HBP concentrations were correlated with the lowest ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PF ratio) during the ICU stay (rho = -0.321, p <0.05). In patients with and without invasive mechanical ventilation, the baseline HBP levels were 152 ng/mL (72-237 ng/mL) and 83 ng/mL (58-108 ng/mL) (p 0.088), respectively. The respective values at day 2 were 223 ng/mL (89-415 ng/mL) and 81 ng/mL (55-97 ng/mL) (p <0.05). The patients with septic shock/severe sepsis (compared with those without) did not have statistically significant differences in HBP concentrations at baseline or day 2. HBP concentrations are markedly elevated in all critically ill patients with influenza A(H1N1) infection. The increase in HBP concentrations seems to be associated with more pronounced respiratory dysfunction. PMID:23402373

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

    NASA Technical Reports Server (NTRS)

    Ditaranto, R. A.; Sankewitsch, V.

    1989-01-01

    Boeing Helicopters, together with other U.S. Helicopter manufacturers, participated in a finite element applications program to give the United States a superior capability to utilize finite element analysis models in support of helicopter airframe design. The program was sponsored by the NASA Langley Research Center. Under this program, an activity was sponsored to evaluate existing analysis methods applicable to calculate coupled rotor-airframe vibrations. The helicopter used in this evaluation was the AH-1G helicopter. The results of the Boeing Helicopters efforts are summarized. The planned analytical procedure is reviewed. Changes to the planned procedure are discussed, and results of the correlation study are presented.

  6. Characterization of the 20-Ah nickel-cadmium cell used for energy storage on the Orbiting Astronomical Observatory

    NASA Technical Reports Server (NTRS)

    Ford, F. E.

    1972-01-01

    Tests were conducted on 20-Ah sealed nickel cadmium cells to evaluate initial and long-term performance at various charge rates, temperatures and voltage-control levels. An average ampere-hour recharge of 103 percent per orbit at 13 C was able to maintain cell capacity; required watt-hour recharge on an orbital basis was 8 to 10 percent greater than required ampere-hour recharge. Cells exhibited an early life burn-in characteristic. A discharge after periods of repetitive cycling yielded two voltage plateaus which were temporarily eliminated by the discharge.

  7. 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

  8. 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

  9. 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. PMID:24519544

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

    PubMed

    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; Yu, Hongjie; Chen, Enfu

    2016-04-01

    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

  11. 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

  12. 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

  13. Prostaglandin E2-mediated upregulation of neuroexcitation and persistent tetrodotoxin-resistant Na(+) currents in Ah-type trigeminal ganglion neurons isolated from adult female rats.

    PubMed

    Liu, H; Duan, S-R

    2016-04-21

    Prostaglandin-E2 (PGE2) is a very important inflammatory mediator and PGE2-mediated neuroexcitation in sex-specific distribution of Ah-type trigeminal ganglion neurons (TGNs) isolated from adult female rats is not fully addressed. The whole-cell patch-clamp experiment was performed to verify the effects of PGE2, forskolin, and GPR30-selective agonist (G-1) on action potential (AP) and tetrodotoxin-resistant (TTX-R) Na(+) currents in identified Ah-type TGNs. The results showed that the firing frequency was increased in Ah- and C-types by PGE2, which was simulated by forskolin and inhibited by Rp-cyclic adenosine monophosphate (cAMP), while G-1 mimicked this effect only in Ah-types, which was abolished by GPR30-selective antagonist (G-15). Although the amplitude of AP was increased in Ah- and C-types, increased maximal upstroke velocity was confirmed only in Ah-types, suggesting distinct alternations in current density and/or voltage-dependent property of Na(+) channels. With 1.0μM PGE2, TTX-R Na(+) currents were upregulated without changing the current-voltage relationship and voltage-dependent activation in C-types, however, the TTX-R Na(+) current was augmented in Ah-types, peaked voltage and the voltage-dependent activation were both shifted toward hyperpolarized direction with faster slope. Intriguingly, the low-threshold persistent TTX-R component was activated from -60mV and increased almost double at -30mV compared with ∼30-40% increment of TTX-R component being activated at ∼-10mV. Additionally, the change in TTX-R component of Ah-types was equivalent well with that in C-type TGNs. Taken these data together, we conclude that PGE2 modulates the neuroexcitation via cAMP-mediated upregulation of TTX-R Na(+) currents in both cell-types with hormone-dependent feature, especially persistent TTX-R Na(+) currents in sex-specific distribution of myelinated Ah-type TGNs. PMID:26868972

  14. 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

  15. The licorice flavonoid isoliquiritigenin reduces DNA-binding activity of AhR in MCF-7 cells.

    PubMed

    Wong, Tsz Yan; Lin, Shu-mei; Poon, Ching Ho; Leung, Lai K

    2014-09-25

    Licorice is derived from the rhizomes of Glycyrrhiza glabra. It has been used for confectioneries or culinary purposes. The rhizomes contain many flavonoidal compounds that have been shown to be biologically active. In the present study, effect of the licorice flavonoid isoliquiritigenin (ILN) on polycyclic aromatic hydrocarbon (PAH)-induced XRE transactivation and the downstream expression were investigated in MCF-7 cells. The environmental toxicant PAHs are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by cytochrome P450 (CYP) 1 enzymes. Reporter gene assay revealed that ILN reduced XRE transactivation triggered by 7,12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-Tetrachlorodibenzodioxin (TCDD). Our EMSA results also demonstrated that the flavonoid diminished DMBA-induced XRE binding. The reduced transactivation could be the result of a decreased amount of AhR translocating from cytosol to nucleus as shown in Western analysis. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that expressions of genes with XRE-containing promoters, including CYP1A1, 1A2, and 1B1, followed the same pattern of XRE transactivation. The present study illustrated that ILN might downregulate PAH-induced expressions through antagonizing AhR translocation. PMID:25110319

  16. 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

  17. 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

  18. 0.4 Ah class graphite/LiMn 2O 4 lithium-ion battery prototypes

    NASA Astrophysics Data System (ADS)

    Appetecchi, Giovanni Battista; Prosini, Pier Paolo

    0.4 Ah lithium-ion battery prototypes, developed within a national project devoted to development of power sources for consumer applications, have been fabricated and tested. A novel, intrinsically porous, PVdF-HFP/MgO composite separator, capable to be hot-laminated onto PVDF-HFP-based electrodes without losing its ability to retain liquid electrolyte, was developed. The devices were assembled by direct lamination of the components, namely graphite anode tapes, PVDF-HFP/MgO separators and LiMn 2O 4 cathode films. The prototypes, formed by a stack of 12 single cells connected in parallel, need no external pressure to maintain contact between the layers. The battery performance was evaluated in terms of capacity, cycle life, energy and power density at different rates. The capability of prototypes to uptake liquid electrolyte was also investigated. The results have indicated the feasibility to scale-up lithium-ion cells to manufacture 0.4 Ah class battery prototypes showing good cycling performance.

  19. Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus

    PubMed Central

    Egawa, Yumi; Ohfuji, Satoko; Fukushima, Wakaba; Yamazaki, Yuko; Morioka, Tomoaki; Emoto, Masanori; Maeda, Kazuhiro; Inaba, Masaaki; Hirota, Yoshio

    2014-01-01

    Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response. PMID:24717236

  20. [Cases of children with influenza AH1N1/2009 in the district of Lodz in two epidemic waves].

    PubMed

    Majda-Stanisławska, Ewa; Sobieraj, Iwona

    2011-01-01

    High influenza morbidity due to new antigenic strain AH1N1 was announced in Mexico in spring 2009. Influenza pandemic caused by the virus AH1N1/2009 spread around the world. Two pandemic waves were noted in most European countries: the first one was due to summer months migration, the second wave started in the beginning of common influenza season. We present features of both waves in children from the district of Lodz. We describe mild clinical course in 14 children who came from holiday in Spain with influenza and who were hospitalized and treated with osltamimivir due to unpredictable course of new influenza. We also present 22 influenza cases of the autumn pandemic wave, when children with severe complications of influenza and children from high risk groups were hospitalized and treated with antivirals. Experience that we have gained during 2009 influenza pandemic indicates that International Influenza Control System is very efficient, however more flexibility is required in application of treatment and prophylaxis procedures with new influenza strains. Applied methods of control should mostly depend on the virulence of pandemic strain. PMID:22390048

  1. 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.

  2. 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

  3. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.

    PubMed

    Guo, Juan; Zhou, Yongjin J; Hillwig, Matthew L; Shen, Ye; Yang, Lei; Wang, Yajun; Zhang, Xianan; Liu, Wujun; Peters, Reuben J; Chen, Xiaoya; Zhao, Zongbao K; Huang, Luqi

    2013-07-16

    Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids. PMID:23812755

  4. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts

    PubMed Central

    Guo, Juan; Zhou, Yongjin J.; Hillwig, Matthew L.; Shen, Ye; Yang, Lei; Wang, Yajun; Zhang, Xianan; Liu, Wujun; Peters, Reuben J.; Chen, Xiaoya; Zhao, Zongbao K.; Huang, Luqi

    2013-01-01

    Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids. PMID:23812755

  5. Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]methionine.

    PubMed

    Kubota, K; Matsuzawa, T; Fujiwara, T; Sato, T; Tada, M; Ido, T; Ishiwata, K

    1989-08-01

    For the evaluation of tumor imaging with L-[methyl-11C]methionine (11C-Met), a basic study on the differentiation of tumor from inflammation with 11C-Met and a comparison of the diagnostic value of the image with that obtained using 67Ga citrate, a conventional scintigraphic agent, are important. 11C-Met accumulations into inflammatory lesions, AH109A tumor and normal tissues of rats were examined by means of a tissue distribution study. Aseptic inflammatory lesions on the back of Donryu rats induced by croton oil and 1.5% carrageenan showed significantly lower accumulations of 11C-Met than the AH109A tumor. Histologically, croton oil induced granulomatous inflammation and carrageenan, acute exudative inflammation. Whole-body autoradiography with 14C-Met, a substitute for 11C-Met, was negative in the carrageenan lesion and showed a slightly increased activity at the periphery of the croton oil lesion, in contrast with the high tumor activity. Whole-body autoradiography with 67Ga citrate was performed to compare the imaging ability with that of 14C-Met; it showed high activities in the tumor, bone, and intestine, and a broad increased activity at the periphery of the croton oil lesion, but was negative in the carrageenan lesion. 11C-Met accumulations in the inflammations were very low and clinical application with positron emission tomography, should be useful for the differential diagnosis of tumor from inflammation. PMID:2511187

  6. Estimating time to onset of swine influenza symptoms after initial novel A(H1N1v) viral infection.

    PubMed

    Tom, B D M; Van Hoek, A J; Pebody, R; McMenamin, J; Robertson, C; Catchpole, M; De Angelis, D

    2011-09-01

    Characterization of the incubation time from infection to onset is important for understanding the natural history of infectious diseases. Attempts to estimate the incubation time distribution for novel A(H1N1v) have been, up to now, based on limited data or peculiar samples. We characterized this distribution for a generic group of symptomatic cases using laboratory-confirmed swine influenza case-information. Estimates of the incubation distribution for the pandemic influenza were derived through parametric time-to-event analyses of data on onset of symptoms and exposure dates, accounting for interval censoring. We estimated a mean of about 1·6-1·7 days with a standard deviation of 2 days for the incubation time distribution in those who became symptomatic after infection with the A(H1N1v) virus strain. Separate analyses for the <15 years and ≥ 15 years age groups showed a significant (P<0·02) difference with a longer mean incubation time in the older age group. PMID:21087539

  7. 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

  8. 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

  9. 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

  10. Prevalence of influenza A/H3N2 virus in northern Iran from 2011 to 2013

    PubMed Central

    Haghshenas, Mohammadreza; Jafarian, Elham; Babamahmoodi, Farhang; Tabrizi, Ahmad; Nandoost, Sharbano; Alizadeh-Navaei, Reza

    2015-01-01

    Background: Influenza A virus is the most virulent human pathogen and causes the most serious problem. Having epidemiological knowledge about this disease is important. The aim of this study was to determine the prevalence of influenza A/H3N2 virus infection in northern Iran from 2011 to 2013 using the real-time polymerase chain reaction (RT-PCR). Methods: In this cross-sectional study 57 samples were collected from patients with influenza-like illness (T≥ 38 °C and cough or sore throat. Influenza-RNA was extracted from the samples using PureLinkTM Viral RNA/DNA Kit. RT-PCR was one using SuperScript III Platinum, Quantitive Real Time PCR system from invitrogen with a specific type of primers and probs. All samples were examined in the Influenza laboratory of Mazandaran University of Medical Sciences. Results: The mean age of patients was 38.2±14.5 year, 278 (48.69%) were males and 293 (51.31%) females. A total number of 201 patients (35.2%) were diagnosed as influenza A1 H3 N2 infection. Conclusion: The results show that the prevalence of A/H3N2 in the North of Iran is considerable and needs more attention for preventive measures. PMID:26221512

  11. Coupled rotor/fuselage dynamic analysis of the AH-1G helicopter and correlation with flight vibrations data

    NASA Technical Reports Server (NTRS)

    Corrigan, J. C.; Cronkhite, J. D.; Dompka, R. V.; Perry, K. S.; Rogers, J. P.; Sadler, S. G.

    1989-01-01

    Under a research program designated Design Analysis Methods for VIBrationS (DAMVIBS), existing analytical methods are used 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. The analytical representation of the fuselage structure is based on a NASTRAN finite element model (FEM), which has been developed, extensively documented, and correlated with ground vibration test. One procedure that was used for predicting coupled rotor-fuselage vibrations using the advanced Rotorcraft Flight Simulation Program C81 and NASTRAN is summarized. Detailed descriptions of the analytical formulation of rotor dynamics equations, fuselage dynamic equations, coupling between the rotor and fuselage, and solutions to the total system of equations in C81 are included. Analytical predictions of hub shears for main rotor harmonics 2p, 4p, and 6p generated by C81 are used in conjunction with 2p OLS measured control loads and a 2p lateral tail rotor gearbox force, representing downwash impingement on the vertical fin, to excite the NASTRAN model. NASTRAN is then used to correlate with measured OLS flight test vibrations. Blade load comparisons predicted by C81 showed good agreement. In general, the fuselage vibration correlations show good agreement between anslysis and test in vibration response through 15 to 20 Hz.

  12. 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

  13. 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

  14. Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009-2010: cohort and case-control study.

    PubMed

    Castilla, Jesús; Morán, Julio; Martínez-Artola, Víctor; Fernández-Alonso, Mirian; Guevara, Marcela; Cenoz, Manuel García; Reina, Gabriel; Alvarez, Nerea; Arriazu, Maite; Elía, Fernando; Salcedo, Esther; Barricarte, Aurelio

    2011-08-11

    We defined a population-based cohort (596,755 subjects) in Navarre, Spain, using electronic records from physicians, to evaluate the effectiveness of the monovalent A(H1N1)2009 vaccine in preventing influenza in the 2009-2010 pandemic season. During the 9-week period of vaccine availability and circulation of the A(H1N1)2009 virus, 4608 cases of medically attended influenza-like illness (MA-ILI) were registered (46 per 1000 person-years). After adjustment for sociodemographic covariables, outpatient visits and major chronic conditions, vaccination was associated with a 32% (95% CI: 8-50%) reduction in the overall incidence of MA-ILI. In a test negative case-control analysis nested in the cohort, swabs from 633 patients were included, and 123 were confirmed for A(H1N1)2009 influenza. No confirmed case had received A(H1N1)2009 vaccine versus 9.6% of controls (p<0.001). The vaccine effectiveness in preventing laboratory-confirmed influenza was 89% (95% CI: 36-100%) after adjusting for age, health care setting, major chronic conditions and period. Pandemic vaccine was effective in preventing MA-ILI and confirmed cases of influenza A(H1N1)2009 in the 2009-2010 season. PMID:21723358

  15. 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

  16. 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

  17. 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

  18. Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

    PubMed Central

    Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2011-01-01

    Background Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. Methodology/Principal Findings Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR+/+ but not AhR -/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. Conclusions/Significance These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation. PMID:21858153

  19. 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.

  20. 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. PMID:26271901

  1. 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

  2. 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. PMID:26945061

  3. 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

  4. 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

  5. Selectivity profile of the novel muscarinic antagonist UH-AH 37 determined by the use of cloned receptors and isolated tissue preparations.

    PubMed Central

    Wess, J.; Lambrecht, G.; Mutschler, E.; Brann, M. R.; Dörje, F.

    1991-01-01

    1. Functional in vitro experiments were carried out to determine the antimuscarinic potencies of the pirenzepine derivative UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-dibenzo- [b,e] [1,4] diazepine-11-one hydrochloride) at M1 muscarinic receptors of rabbit vas deferens, M2 receptors of rat left atria and M3 receptors of rat ileum. Furthermore, N-[3H]-methylscopolamine competition binding experiments were performed to obtain its affinities for the five cloned human muscarinic receptors (m1-m5) stably expressed in CHO-K1 cells. Pirenzepine served as a reference drug throughout all experiments. 2. In all preparations used, UH-AH 37 interacted with muscarinic receptors in a fashion characteristic of a simple competitive antagonist. 3. In the functional studies, UH-AH 37, like pirenzepine, showed high affinity for M1 (pA2 8.49) and low affinity for M2 muscarinic receptors (pA2 6.63). In contrast to pirenzepine, UH-AH 37 also displayed high affinity for M3 receptors (pA2 8.04). 4. In agreement with its functional profile, UH-AH 37 bound with highest affinity to m1 (pKi 8.74) and with lowest affinity to m2 receptors (pKi 7.35). Moreover, it showed a 7 fold higher affinity for m3 (pKi 8.19) than for m2 receptors, whereas pirenzepine bound to both receptors with low affinities. 5. The binding affinity of UH-AH 37 for m4 and m5 receptors (pKi 8.32 for both receptors) was only ca. 2.5 fold lower than that for m1 receptors, while the corresponding affinity differences were 6 and 13 fold in case of pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043926

  6. The inner-sphere reorganization energies for AH{sub 2} + AH{sub 2}{sup +(-)} (A = Al, Si, P, S) electron self-exchange reactions in electron-transfer processes from ab initio calculations

    SciTech Connect

    Yuxiang Bu; Zhaohua Cao; Zailun Yang

    1995-08-15

    This article presents an application of the accurate calculation scheme proposed recently for the inner-sphere reorganization energies of molecules of the type AH{sub 2} (A = Al, Si, P, and S). A reasonable extension has been made. The inner-sphere reorganization energies for the title thermal electron self-exchange reactions are calculated in terms of ab initio MO self-consistent field method (HFSCF) at different basis-set levels (6-31G**, 6-31 + G**, DZ, and DZP) and the involved parameters are also determined. These calculated results have been calibrated by comparing optimized molecular geometrical parameters and corresponding energy properties with the experimental findings or other theoretical values. An approximation, in which the contribution from the bond length-bond angle to the potential energy surface is neglected, is adopted in constructing the calculation formulas via the function model. Its adequacy is discussed. Agreement among different calculation schemes is analyzed. 32 refs., 2 tabs.

  7. 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

  8. 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

  9. 2009 A(H1N1) Seroconversion Rates and Risk Factors among the General Population in Vientiane Capital, Laos

    PubMed Central

    Kieffer, Alexia; Paboriboune, Phimpha; Crépey, Pascal; Flaissier, Bruno; Souvong, Vimalay; Steenkeste, Nicolas; Salez, Nicolas; Babin, François-Xavier; Longuet, Christophe; Carrat, Fabrice; Flahault, Antoine; de Lamballerie, Xavier

    2013-01-01

    Objective To assess 2009 A(H1N1) seroconversion rates and their determinants within an unvaccinated population in Vientiane Capital, Laos. Methods CoPanFlu Laos, a general population cohort of 807 households and 4,072 participants was established in March 2010. Sociodemographic data, epidemiological data, and capillary blood samples were collected from all the household members in March, and again in October 2010, in order to assess the level of antibodies to 2009 A(H1N1) with the haemagglutination inhibition assay. 2009 A(H1N1) seroconversion was defined as a fourfold or greater increase in titre between inclusion and follow-up. Determinants for pandemic influenza infection were studied using the generalized estimating equations model, taking household clustering into account. Results Between March and November 2010, 3,524 paired sera were tested. Prior to the pandemic, our cohort was almost completely vaccine-naive for seasonal influenza. The overall seroconversion rate among nonvaccinated individuals (n = 2,810) was 14.3% (95%CI [13.0, 15.6]), with the highest rate for participants under 20 yo (19.8%, 95%CI [17.4, 22.4]) and the lowest rate for participants over 60 yo (6.5%, 95%CI [3.7, 10.4]). Participants with lower baseline titres had significantly higher infection rates, with a dose-effect relationship. Odds ratios (ORs) ranged from 76.5 (95%CI [27.1, 215.8]), for those with a titre at inclusion of 1∶10, to 8.1 (95%CI [3.3, 20.4]), for those with a titre of 1∶40. Having another household member with a titre ≥1∶80 was associated with a higher likelihood of immunity (OR = 3.3, 95%CI [2.8, 3.9]). Conclusion The determinants and age distribution for seroconversion within a vaccine-naive population were similar to those found in developed countries. This pandemic was characterized by strong epidemiological determinants, regardless of geographical zone and level of development. Moreover, we detected pre-existing cross-reacting antibodies in

  10. 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

  11. Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

    PubMed

    Gilsdorf, A; Boxall, N; Gasimov, V; Agayev, I; Mammadzade, F; Ursu, P; Gasimov, E; Brown, C; Mardel, S; Jankovic, D; Pimentel, G; Ayoub, I Amir; Elassal, E Maher Labib; Salvi, C; Legros, D; Pessoa da Silva, C; Hay, A; Andraghetti, R; Rodier, G; Ganter, B

    2006-01-01

    Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to

  12. Studies of Influenza A/H1N1 A/Tomsk/13/2010 Virus Topology during Development of Infectious Process in Mammals.

    PubMed

    Potapova, O V; Kovner, A V; Anikina, A G; Cherdantseva, L A; Sharkova, T V; Shkurupy, V A; Vasil'eva, E V; Shestopalov, A M

    2016-03-01

    Influenza A/H1N1 A/Tomsk/13/2010 virus registered in Siberia in 2010 proved to be an extremely pathogenic strain. Dynamic study of the topology of this influenza virus strain in the lungs, liver, kidneys, lymph nodes, and great vessels of infected mice was carried out. Influenza A virus was detected by immunohistochemical methods in cells of different histogenesis in all the studied organs throughout the observation period (days 1-30 postinfection), which indicated effective replication and long persistence of influenza A/H1N1 A/Tomsk/13/2010 virus in mammalian cells. PMID:27025855

  13. Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11.

    PubMed

    Lackenby, A; Moran Gilad, J; Pebody, R; Miah, S; Calatayud, L; Bolotin, S; Vipond, I; Muir, P; Guiver, M; McMenamin, J; Reynolds, A; Moore, C; Gunson, R; Thompson, C; Galiano, M; Bermingham, A; Ellis, J; Zambon, M

    2011-01-01

    During the winter period 2010/11 27 epidemiologically unlinked, confirmed cases of oseltamivir-resistant influenza A(H1N1)2009 virus infection have been detected in multiple, geographically dispersed settings. Three of these cases were in community settings, with no known exposure to oseltamivir. This suggests possible onward transmission of resistant strains and could be an indication of a possibility of changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus. PMID:21315056

  14. Impact of live poultry market closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus: an ecological study

    PubMed Central

    Yu, Hongjie; Wu, Joseph T.; Cowling, Benjamin J.; Liao, Qiaohong; Fang, Vicky J.; Zhou, Sheng; Wu, Peng; Zhou, Hang; Lau, Eric H. Y.; Guo, Danhuai; Ni, Michael Y.; Peng, Zhibin; Feng, Luzhao; Jiang, Hui; Luo, Huiming; Li, Qun; Feng, Zijian; Wang, Yu; Yang, Weizhong; Leung, Gabriel M.

    2014-01-01

    Background A novel influenza A(H7N9) virus has emerged in China during the past few months. Inter-species zoonotic transmission appears to be the predominant route of spread. Live poultry markets (LPMs) in the major cities of Shanghai, Hangzhou, Huzhou and Nanjing, where the majority of cases have occurred, were swiftly closed as a precautionary public health measure. Our objective was to quantify the impact of LPM closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus. Methods We used data on the illness onset dates and geographical locations of laboratory-confirmed influenza A(H7N9) cases that were officially announced by 7 June 2013. We constructed a statistical model to explain the patterns in incident cases reported in each city based on the assumption of a constant force of infection prior to closure, and a different constant force of infection after closure. We fitted the model using Markov chain Monte Carlo methods. Findings There were 85 confirmed influenza A(H7N9) cases in Shanghai, Hangzhou, Huzhou and Nanjing out of a total of 130 confirmed cases in mainland China by 7 June 2013. Closure of LPMs in those four cities reduced the risk of human infections by 97%–99% (range 68%–100%) in each city. Given that LPMs were the predominant source of influenza A(H7N9) exposure in those locations, we estimated the mean incubation period to be 3.3 days. Interpretation LPM closures were extremely effective in controlling human risk of influenza A(H7N9). If the influenza A(H7N9) epizootic/epidemic continues, LPM closure should be sustained in at-risk areas and implemented in any urban areas where influenza A(H7N9) reappears in future. In the longer term, evidence-based discussions and deliberations about the role of central slaughtering of all live poultry should be renewed. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special

  15. One-Step Detection of the 2009 Pandemic Influenza A(H1N1) Virus by the RT-SmartAmp Assay and Its Clinical Validation

    PubMed Central

    Kawai, Yuki; Kimura, Yasumasa; Lezhava, Alexander; Kanamori, Hajime; Usui, Kengo; Hanami, Takeshi; Soma, Takahiro; Morlighem, Jean-Étienne; Saga, Satomi; Ishizu, Yuri; Aoki, Shintaro; Endo, Ryuta; Oguchi-Katayama, Atsuko; Kogo, Yasushi; Mitani, Yasumasa; Ishidao, Takefumi; Kawakami, Chiharu; Kurata, Hideshi; Furuya, Yumiko; Saito, Takayuki; Okazaki, Norio; Chikahira, Masatsugu; Hayashi, Eiji; Tsuruoka, Sei-ichi; Toguchi, Tokumichi; Saito, Yoshitomo; Ban, Toshiaki; Izumi, Shinyu; Uryu, Hideko; Kudo, Koichiro; Sakai-Tagawa, Yuko; Kawaoka, Yoshihiro; Hirai, Aizan; Hayashizaki, Yoshihide; Ishikawa, Toshihisa

    2012-01-01

    Background In 2009, a pandemic (pdm) influenza A(H1N1) virus infection quickly circulated globally resulting in about 18,000 deaths around the world. In Japan, infected patients accounted for 16% of the total population. The possibility of human-to-human transmission of highly pathogenic novel influenza viruses is becoming a fear for human health and society. Methodology To address the clinical need for rapid diagnosis, we have developed a new method, the “RT-SmartAmp assay”, to rapidly detect the 2009 pandemic influenza A(H1N1) virus from patient swab samples. The RT-SmartAmp assay comprises both reverse transcriptase (RT) and isothermal DNA amplification reactions in one step, where RNA extraction and PCR reaction are not required. We used an exciton-controlled hybridization-sensitive fluorescent primer to specifically detect the HA segment of the 2009 pdm influenza A(H1N1) virus within 40 minutes without cross-reacting with the seasonal A(H1N1), A(H3N2), or B-type (Victoria) viruses. Results and Conclusions We evaluated the RT-SmartAmp method in clinical research carried out in Japan during a pandemic period of October 2009 to January 2010. A total of 255 swab samples were collected from outpatients with influenza-like illness at three hospitals and eleven clinics located in the Tokyo and Chiba areas in Japan. The 2009 pdm influenza A(H1N1) virus was detected by the RT-SmartAmp assay, and the detection results were subsequently compared with data of current influenza diagnostic tests (lateral flow immuno-chromatographic tests) and viral genome sequence analysis. In conclusion, by the RT-SmartAmp assay we could detect the 2009 pdm influenza A(H1N1) virus in patients' swab samples even in early stages after the initial onset of influenza symptoms. Thus, the RT-SmartAmp assay is considered to provide a simple and practical tool to rapidly detect the 2009 pdm influenza A(H1N1) virus. PMID:22295077

  16. Amino Acid Substitutions That Affect Receptor Binding and Stability of the Hemagglutinin of Influenza A/H7N9 Virus.

    PubMed

    Schrauwen, Eefje J A; Richard, Mathilde; Burke, David F; Rimmelzwaan, Guus F; Herfst, Sander; Fouchier, Ron A M

    2016-01-01

    Receptor-binding preference and stability of hemagglutinin have been implicated as crucial determinants of airborne transmission of influenza viruses. Here, amino acid substitutions previously identified to affect these traits were tested in the context of an A/H7N9 virus. Some combinations of substitutions, most notably G219S and K58I, resulted in relatively high affinity for α2,6-linked sialic acid receptor and acid and temperature stability. Thus, the hemagglutinin of the A/H7N9 virus may adopt traits associated with airborne transmission. PMID:26792744

  17. 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

  18. Combined Administration of MF59-Adjuvanted A/H5N1 Prepandemic and Seasonal Influenza Vaccines: Long-Term Antibody Persistence and Robust Booster Responses 1 Year after a One-Dose Priming Schedule

    PubMed Central

    Lopez, Pio; Caicedo, Yolanda; Sierra, Alexandra; Tilman, Sandrine; Clemens, Ralf

    2013-01-01

    Having previously demonstrated the feasibility of administering A/H5N1 and seasonal influenza vaccine antigens in an MF59-adjuvanted tetravalent formulation, we now report on long-term antibody persistence and responses to a booster dose of a combined seasonal-pandemic, tetravalent influenza vaccine in adults. The primary objective was the evaluation of responses to a booster dose of tetravalent influenza vaccine containing seasonal (A/H1N1, A/H3N2, and B) and avian (A/H5N1, clade 2) influenza virus strains administered to 265 healthy 18- to 40-year-old volunteers 1 year after priming with one or two clade 1 A/H5N1 doses. Secondary objectives were assessment of reactogenicity, safety, and antibody persistence 1 year after priming with a combined seasonal-pandemic, tetravalent vaccine. Responses to seasonal strains met all European licensure criteria; seroprotection rates were 94 to 100%, 100%, and 61 to 90% for A/H1N1, A/H3N2, and B strains, respectively. Anamnestic responses were observed against homologous and heterologous A/H5N1 strains whether priming with one or two A/H5N1 doses, with a monovalent A/H5N1 vaccine, or with a tetravalent vaccine. A single dose of MF59-adjuvanted A/H5N1 vaccine given alone or as part of a fixed combination with a seasonal influenza vaccine was sufficient to prime adult subjects, resulting in robust antigen-specific and cross-reactive antibody responses to heterologous booster immunization 1 year later. These data support the feasibility of incorporating prepandemic priming into seasonal influenza vaccination programs. (This study has been registered at clinicaltrials.gov under registration no. NCT00481065.) PMID:23536690

  19. Enhanced resistance of Saccharomyces cerevisiae to vanillin by expression of lacA from Trametes sp. AH28-2.

    PubMed

    Ji, Lei; Shen, Yu; Xu, Lili; Peng, Bingyin; Xiao, Yazhong; Bao, Xiaoming

    2011-09-01

    Saccharomyces cerevisiae is affected by the presence of certain phenolic compounds such as vanillin during fermentation of pretreated lignocellulosic hydrolysates. Since vanillin can be polymerized in the presence of laccase into compounds with lower toxicity, the laccase gene, lacA, from Trametes sp. AH28-2 was fused to the α-factor signal sequence and transferred into S. cerevisiae CEN.PK strains for secretory expression. Furthermore, the chaperone gene, KAR2, was overexpressed to promote the translocation of laccase. In the presence of 8 mmol/L vanillin, a shorter lag phase was observed in the lacA gene expressing strains. The vanillin-specific conversion rate of the lacA-expressing strain BSJX0A2 was 0.069 g g(-1)biomass h(-1), while it was 0.065 g g(-1)biomass h(-1) in the reference strain. PMID:21727001

  20. Bougainvinones A-H, Peltogynoids from the Stem Bark of Purple Bougainvillea spectabilis and Their Cytotoxic Activity.

    PubMed

    Do, Lien T M; Aree, Thammarat; Siripong, Pongpun; Pham, Tuyen N K; Nguyen, Phung K P; Tip-Pyang, Santi

    2016-04-22

    Eight new peltogynoids, named bougainvinones A-H (1-8), were obtained from the stem bark of Bougainvillea spectabilis. Their structures were elucidated by means of physical data (1D and 2D NMR, HRESIMS) and single-crystal X-ray crystallographic analyses. The peltogynoids, a rare type of modified flavonoids, are reported for the first time from this species of the genus Bougainvillea. All isolated compounds were evaluated for their cytotoxic effects against five cancer cell lines including KB, Hela S-3, HT-29, MCF-7, and HepG2. Among them, compound 7 showed cytotoxicity against five cancer cell lines with IC50 values in the 7.4-9.7 μM range, and compounds 2 and 3 exhibited cytotoxicity against the KB cell line with IC50 values of 6.6 and 9.0 μM. PMID:26963142

  1. Excess mortality monitoring in England and Wales during the influenza A(H1N1) 2009 pandemic.

    PubMed

    Hardelid, P; Andrews, N; Pebody, R

    2011-09-01

    We present the results from a novel surveillance system for detecting excess all-cause mortality by age group in England and Wales developed during the pandemic influenza A(H1N1) 2009 period from April 2009 to March 2010. A Poisson regression model was fitted to age-specific mortality data from 1999 to 2008 and used to predict the expected number of weekly deaths in the absence of extreme health events. The system included adjustment for reporting delays. During the pandemic, excess all-cause mortality was seen in the 5-14 years age group, where mortality was flagged as being in excess for 1 week after the second peak in pandemic influenza activity; and in age groups >45 years during a period of very cold weather. This new system has utility for rapidly estimating excess mortality for other acute public health events such as extreme heat or cold weather. PMID:21439100

  2. 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.

  3. 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.

  4. Acute respiratory distress syndrome (ARDS) complicating influenza A/H1N1v infection--a clinical approach.

    PubMed

    Witczak, Agnieszka; Prystupa, Andrzej; Kurys-Denis, Ewa; Borys, Michał; Czuczwar, Mirosław; Niemcewicz, Marcin; Kocik, Janusz; Michalak, Anna; Pietrzak, Aldona; Chodorowska, Grażyna; Krupski, Witold; Mosiewicz, Jerzy; Tomasiewicz, Krzysztof

    2013-01-01

    ARDS is defined as an acute inflammatory syndrome characterized with bilateral parenchymal lung infiltrates on chest radiograph and PaO2/FiO2 ratio<200 resulting from causes other than acute left ventricular dysfunction. Inflammatory lung lesions may be induced by different disorders, with sepsis being the leading cause of ARDS. Other causes include infectious pneumonia, aspiration of gastric contents, drugs, severe trauma, fat embolism, surface burn, massive blood transfusion. Influenza A/H1N1 infection seems to be responsible for the development of extremely severe type of ARDS with poor response to routine treatment. Despite great progress in the management of ARDS with novel agents and sophisticated techniques, including antimicrobial drugs, extracorporeal membrane oxygenation, prostaglandins, nitric oxide, prostacyclin, exogenous surfactant administration and activated protein C, supportive treatment based mostly on advanced mechanical ventilation in the intensive care units seems to be the most important for the prognosis. PMID:24364461

  5. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer.

    PubMed

    D'Amato, Nicholas C; Rogers, Thomas J; Gordon, Michael A; Greene, Lisa I; Cochrane, Dawn R; Spoelstra, Nicole S; Nemkov, Travis G; D'Alessandro, Angelo; Hansen, Kirk C; Richer, Jennifer K

    2015-11-01

    The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-κB-dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor-treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor-negative status, and shorter overall survival. Our results define an NF-κB-regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype. PMID:26363006

  6. 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

  7. HDAC1 bound to the Cyp1a1 promoter blocks histone acetylation associated with Ah receptor-mediated transactivation

    PubMed Central

    Schnekenburger, Michael; Peng, Li; Puga, Alvaro

    2007-01-01

    Metabolic bioactivation of polycyclic aromatic hydrocarbons, such as the environmental procarcinogen benzo[a]pyrene, is catalyzed by a cytochrome P450 monooxygenase encoded by the substrate-inducible Cyp1a1 gene. Cyp1a1 induction requires trans-activation by the heterodimeric transcriptional complex formed by the liganded Ah receptor (AHR) and its partner, ARNT. Previously, we showed that constitutively bound HDAC1 dissociates from Cyp1a1 promoter chromatin after ligand-mediated induction, concomitantly with the recruitment of AHR/ARNT complexes and p300. Here, we investigated the hypothesis that HDAC1 binding maintains the Cyp1a1 gene in a silenced state in uninduced cells. We find that Cyp1a1 induction by the AHR/ARNT is associated with modification of specific chromatin marks, including hyperacetylation of histone H3K14 and H4K16, trimethylation of histone H3K4, and phosphorylation of H3S10. HDAC1 and DNMT1 form complexes on the Cyp1a1 promoter of uninduced cells but HDAC1 inhibition alone is not sufficient to induce Cyp1a1 expression, although it allows for the hyperacetylation of H3K14 and H4K16 to levels similar to those found in B[a]P-induced cells. These results show that by blocking modification of histone marks, HDAC1 plays a central role in Cyp1a1 expression and that its removal is a necessary but not sufficient condition for Cyp1a1 induction, underscoring the requirement for a concerted series of chromatin remodeling events to complete the initial steps of gene trans-activation by the Ah receptor. PMID:17707923

  8. Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period

    PubMed Central

    Fang, Vicky J.; Feng, Luzhao; Tsang, Tim K.; Jiang, Hui; Wu, Peng; Zheng, Jiandong; Lau, Eric H. Y.; Qin, Ying; Peng, Zhibin; Peiris, J. S. Malik; Yu, Hongjie; Cowling, Benjamin J.

    2016-01-01

    Background In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. Methods and Findings We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4–4.1), compared to a mean of 3.3 days (95% CrI: 2.9–3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47–1.97). Conclusions We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration. PMID:26885816

  9. Environmental Sampling for Avian Influenza A(H7N9) in Live-Poultry Markets in Guangdong, China

    PubMed Central

    Kang, Min; He, Jianfeng; Song, Tie; Rutherford, Shannon; Wu, Jie; Lin, Jinyan; Huang, Guofeng; Tan, Xiaohua; Zhong, Haojie

    2015-01-01

    Background To provide an increased understanding of avian influenza A(H7N9) activity in live-poultry market in space and time and hence improve H7N9 epidemic control, an ongoing environmental sampling program in multiple live-poultry markets across Guangdong, China was conducted during March 2013–June 2014. Methods A total of 625 live-poultry markets throughout 21 prefecture areas took part in the study. A total of 10 environmental sites in markets for sampling were identified to represent 4 different poultry-related activity areas. At least 10 environmental samples were collected from each market every month. The real time RT-PCR was performed to detect the avian influenza A(H7N9) virus. Field survey was conducted to investigate the sanitation status of live-poultry markets. Results There were 109 human infections with H7N9 avian influenza in Guangdong, of which 37 (34%) died. A total of 18741 environmental swabs were collected and subjected to real-time RT-PCR test, of which 905(4.83%) were found positive for H7N9 virus. There were 201 (32.16%) markets affected by H7N9 in 16 prefecture areas. The detection of H7N9 virus in markets spiked in winter months. 63.33% markets (38/60) had no physical segregation for poultry holding, slaughter or sale zones. Closing live-poultry market significantly decreased the H7N9 detection rate from 14.83% (112/755) to 1.67% (5/300). Conclusions This study indicates the importance of live-poultry market surveillance based on environmental sampling for H7N9 Avian Influenza control. Improving live-poultry market management and sanitation and changing consumer practices are critical to reduce the risk of H7N9 infection. PMID:25933138

  10. 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

  11. 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

  12. 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.

  13. The Spread of Influenza A(H1N1)pdm09 Virus in Madagascar Described by a Sentinel Surveillance Network

    PubMed Central

    Rajatonirina, Soatiana; Heraud, Jean-Michel; Orelle, Arnaud; Randrianasolo, Laurence; Razanajatovo, Norosoa; Rajaona, Yolande Raoelina; Randrianarivo-Solofoniaina, Armand Eugène; Rakotomanana, Fanjasoa; Richard, Vincent

    2012-01-01

    Background The influenza A(H1N1)pdm09 virus has been a challenge for public health surveillance systems in all countries. In Antananarivo, the first imported case was reported on August 12, 2009. This work describes the spread of A(H1N1)pdm09 in Madagascar. Methods The diffusion of influenza A(H1N1)pdm09 in Madagascar was explored using notification data from a sentinel network. Clinical data were charted to identify peaks at each sentinel site and virological data was used to confirm viral circulation. Results From August 1, 2009 to February 28, 2010, 7,427 patients with influenza-like illness were reported. Most patients were aged 7 to 14 years. Laboratory tests confirmed infection with A(H1N1)pdm09 in 237 (33.2%) of 750 specimens. The incidence of patients differed between regions. By determining the epidemic peaks we traced the diffusion of the epidemic through locations and time in Madagascar. The first peak was detected during the epidemiological week 47-2009 in Antananarivo and the last one occurred in week 07-2010 in Tsiroanomandidy. Conclusion Sentinel surveillance data can be used for describing epidemic trends, facilitating the development of interventions at the local level to mitigate disease spread and impact. PMID:22615893

  14. Genetic and antigenic characterization of hemagglutinin of influenza A/H3N2 virus from the 2015 season in Thailand.

    PubMed

    Tewawong, Nipaporn; Suntronwong, Nungruthai; Vichiwattana, Preeyaporn; Vongpunsawad, Sompong; Theamboonlers, Apiradee; Poovorawan, Yong

    2016-10-01

    Antigenic changes in the HA1 domain of the influenza A/H3N2 hemagglutinin (HA) present a challenge in the design of the annual influenza vaccine. We examined the genetic variability in the nucleotide and amino acid of encoding HA1 sequences of the influenza A/H3N2 virus during the 2015 influenza season in Thailand. Toward this, the HA genes of 45 influenza A/H3N2 strains were amplified and sequenced. Although a clade 3C.3a strain (A/Switzerland/9715293/2013) was chosen for the 2015 vaccine, phylogenetic analysis demonstrated that strains belonging to clade 3C.2a (96 %) instead of clade 3C.3a (4 %) were circulating that year. Sequence analysis showed that seven codons were under positive selection, five of which were located inside the antigenic epitopes. The percentages of the perfect match vaccine efficacy (VE) estimated by the P epitope model against circulating strains suggested antigenic drift of the dominant epitopes A and B, which contributed to reduced VE of the 2015 vaccine. However, the 2016 vaccine strain (A/Hong Kong/4801/2014) was closely related and well matched against the circulating strain (mean of VE = 79.3 %). These findings provide data on the antigenic drift of the influenza A/H3N2 virus circulating in Thailand and further support continual monitoring and surveillance of the antigenic changes on HA1. PMID:27146171

  15. 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

  16. 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

  17. 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. PMID:24582319

  18. 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...

  19. CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis.

    PubMed

    Cibrian, Danay; Saiz, María Laura; de la Fuente, Hortensia; Sánchez-Díaz, Raquel; Moreno-Gonzalo, Olga; Jorge, Inmaculada; Ferrarini, Alessia; Vázquez, Jesús; Punzón, Carmen; Fresno, Manuel; Vicente-Manzanares, Miguel; Daudén, Esteban; Fernández-Salguero, Pedro M; Martín, Pilar; Sánchez-Madrid, Francisco

    2016-08-01

    The activation marker CD69 is expressed by skin γδ T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by γδ T cells, which contributed to the development of psoriasis induced by IL-23. CD69 associated with the aromatic-amino-acid-transporter complex LAT1-CD98 and regulated its surface expression and uptake of L-tryptophan (L-Trp) and the intracellular quantity of L-Trp-derived activators of AhR. In vivo administration of L-Trp, an inhibitor of AhR or IL-22 abrogated the differences between CD69-deficient mice and wild-type mice in skin inflammation. We also observed LAT1-mediated regulation of AhR activation and IL-22 secretion in circulating Vγ9(+) γδ T cells of psoriatic patients. Thus, CD69 serves as a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues. PMID:27376471

  20. 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

  1. 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). PMID

  2. 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

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

    PubMed

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

    2015-10-01

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

  4. 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.

  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. A Comparison between Cytotoxicity Induced by Two Resin Based Sealers (2Seal and AH Plus) in Saos-2 and MG-63 Cell Lines

    PubMed Central

    Ehsani, Maryam; Zabihi, Ebrahim; Gharouee, Hamed

    2012-01-01

    The aim of this study was to evaluate and compare the cytotoxicity induced by two resin-based sealers, 2Seal and AH Plus, in two osteoblast-like cell lines, MG-63 and Saos-2. Using sterile discs of both sealers in complete media, 24- and 72-h extracts were prepared. The extracts were exchanged with Saos-2 or MG-63 cell culture media at 75% confluence, and after 24 h incubation, cell viability tests were performed for each extract and cell line using MTT and trypan blue dye exclusion assays. Corresponding incubated media were used as negative control groups. For both extracts and sealers, cytotoxicity was observed in both cell lines. For Saos-2, there was no statistical difference in toxicity between the sealers for either extract (p > 0.05). For MG-63, the 2Seal 24-h extract and the AH Plus 72-h extract had greater cytotoxicity than the other extracts (p < 0.05(. Both AH Plus and 2Seal demonstrated significant cytotoxicity in these two cell lines. In contrast to 2Seal, the cytotoxicity of AH Plus in the MG-63 cell line increased with extraction time from 24 to 72 h. The AH Plus and 2Seal 24-h extracts showed different levels of cytotoxicity in the MG-63 cell line, while in the Saos-2 cell line there were no detectable differences. This may reflect higher sensitivity of the MG-63 cell line compared to Saos-2 toward cytotoxicity induced by these two sealers, or different kinetics of toxicant release from the sealers. PMID:24551778

  7. 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. PMID:24105757

  8. 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

  9. 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

  10. TCDD and a Putative Endogenous AhR Ligand, ITE, Elicit the Same Immediate Changes in Gene Expression in Mouse Lung Fibroblasts

    PubMed Central

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

    2010-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, mediates toxicity of several classes of xenobiotics and also has important physiological roles in differentiation, reproduction, and immunity, although the endogenous ligand(s) mediating these functions is/are as yet unidentified. One candidate endogenous ligand, 2-(1′H-indolo-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), is a potent AhR agonist in vitro, activates the murine AhR in vivo, but does not induce toxicity. We hypothesized that ITE and the toxic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may modify transcription of different sets of genes to account for their different toxicity. To test this hypothesis, primary mouse lung fibroblasts were exposed to 0.5μM ITE, 0.2nM TCDD, or vehicle for 4 h, and total gene expression was evaluated using microarrays. After this short-term and low-dose treatment, several hundred genes were changed significantly, and the response to ITE and TCDD was remarkably similar, both qualitatively and quantitatively. Induced gene sets included the expected battery of AhR-dependent xenobiotic-metabolizing enzymes, as well as several sets that reflect the inflammatory role of lung fibroblasts. Real time quantitative RT-qPCR assay of several selected genes confirmed these microarray data and further suggested that there may be kinetic differences in expression between ligands. These data suggest that ITE and TCDD elicit an analogous change in AhR conformation such that the initial transcription response is the same. Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible. PMID:19933214

  11. Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children

    PubMed Central

    2012-01-01

    Background Toll-like receptors (TLRs) form an essential part of the innate immune system, which plays a fundamental role in rapidly and effectively controlling infections and initiating adaptive immunity. There are no published data concerning the importance of polymorphisms of TLRs in conditioning susceptibility to influenza or the severity of the disease. The aim of this study was to evaluate whether selected polymorphisms of TLR2, TLR3 and TLR4 influence the incidence and clinical picture of pandemic A/H1N1/2009 influenza. Results The study involved 272 healthy children attending our Emergency Room for influenza-like illness (ILI), including 51 (18.8%) with pandemic A/H1N1/2009 influenza as revealed by real-time polymerase chain reaction, and 164 healthy controls examined after minor surgery. Genomic DNA was extracted from whole blood samples and five single-nucleotide polymorphisms (SNPs) were studied: TLR2 rs5743708, TLR3 rs5743313, TLR3 rs5743315, TLR4 rs4986790 and TLR4 rs4986791. The TLR3 rs5743313/CT polymorphism was found in all of the children with pneumonia and influenza infection, but in a significantly smaller number of those with A/H1N1/2009 influenza without pneumonia (<0.0001). TLR2, TLR3 rs5743315/AC and TLR4 polymorphisms were equally distributed in all of the groups regardless of the presence of the pandemic A/H1N1/2009 virus and clinical diagnosis. Viral load was comparable in all of the study groups. Conclusions There is a close relationship between the presence of TLR3 rs5743313/CT and an increased risk of pneumonia in children infected by the pandemic A/H1N1/2009 influenza virus. PMID:23151015

  12. 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

  13. Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian evidence synthesis

    PubMed Central

    Pebody, R G; Paterson, B J; Tom, B D M; Birrell, P J; Charlett, A; Lipsitch, M; Angelis, D De

    2011-01-01

    Objective To assess the impact of the 2009 A/H1N1 influenza pandemic in England during the two waves of activity up to end of February 2010 by estimating the probabilities of cases leading to severe events and the proportion of the population infected. Design A Bayesian evidence synthesis of all available relevant surveillance data in England to estimate severity of the pandemic. Data sources All available surveillance systems relevant to the pandemic 2009 A/H1N1 influenza outbreak in England from June 2009 to February 2010. Pre-existing influenza surveillance systems, including estimated numbers of symptomatic cases based on consultations to the health service for influenza-like illness and cross sectional population serological surveys, as well as systems set up in response to the pandemic, including follow-up of laboratory confirmed cases up to end of June 2009 (FF100 and Fluzone databases), retrospective and prospective follow-up of confirmed hospitalised cases, and reported deaths associated with pandemic 2009 A/H1N1 influenza. Main outcome measures Age specific and wave specific probabilities of infection and symptomatic infection resulting in hospitalisation, intensive care admission, and death, as well as infection attack rates (both symptomatic and total). The probabilities of intensive care admission and death given hospitalisation over time are also estimated to evaluate potential changes in severity across waves. Results In the summer wave of A/H1N1 influenza, 0.54% (95% credible interval 0.33% to 0.82%) of the estimated 606 100 (419 300 to 886 300) symptomatic cases were hospitalised, 0.05% (0.03% to 0.08%) entered intensive care, and 0.015% (0.010% to 0.022%) died. These correspond to 3200 (2300 to 4700) hospital admissions, 310 (200 to 480) intensive care admissions, and 90 (80 to 110) deaths in the summer wave. In the second wave, 0.55% (0.28% to 0.89%) of the 1 352 000 (829 900 to 2 806 000) estimated symptomatic cases were

  14. 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

  15. 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

  16. 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

  17. 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

  18. Molecular characterization of the predominant influenza A(H1N1)pdm09 virus in Mexico, December 2011-February 2012.

    PubMed

    de la Rosa-Zamboni, Daniela; Vázquez-Pérez, Joel A; Avila-Ríos, Santiago; Carranco-Arenas, Ana Paola; Ormsby, Christopher E; Cummings, Craig A; Soto-Nava, Maribel; Hernández-Hernández, Víctor A; Orozco-Sánchez, Carmen O; la Barrera, Claudia Alvarado-de; Pérez-Padilla, Rogelio; Reyes-Terán, Gustavo

    2012-01-01

    When the A(H1N1)pdm09 pandemic influenza virus moved into the post-pandemic period, there was a worldwide predominance of the seasonal influenza A(H3N2) and B viruses. However, A(H1N1)pdm09 became the prevailing subtype in the 2011-2012 influenza season in Mexico and most of Central America. During this season, we collected nasopharyngeal swabs of individuals presenting with influenza-like illness at our institution in Mexico City. Samples were tested for seasonal A(H3N2) and B influenza viruses, as well as A(H1N1)pdm09 by real-time reverse transcription-polymerase chain reaction. Of 205 samples tested, 46% were positive to influenza, all of them A(H1N1)pdm09. The clinical characteristics of patients showed a similar pattern to the 2009 pandemic cases. Using next generation sequencing, we obtained whole genome sequences of viruses from 4 different patients, and in 8 additional viruses we performed partial Sanger sequencing of the HA segment. Non-synonymous changes found in the Mexican isolates with respect to the prototype isolate H1N1 (A/California/04/2009) included HA S69T, K163R and N260D unique to 2012 Mexican and North American isolates and located within or adjacent to HA antigenic sites; HA S143G, S185T, A197T and S203T previously reported in viruses from the 2010-2011 season, located within or adjacent to HA antigenic sites; and HA E374K located in a relevant site for membrane fusion. All Mexican isolates had an oseltamivir-sensitive genotype. Phylogenetic analysis with all 8 influenza gene segments showed that 2012 Mexican sequences formed a robust, distinct cluster. In all cases, 2012 Mexican sequences tended to group with 2010-2011 Asian and European sequences, but not with 2009 Mexican sequences, suggesting a possible recent common ancestor between these latter regions and the 2012 Mexican viruses. It remains to be defined if these viral changes represent an important antigenic drift that would enable viral immune evasion and/or affect influenza vaccine

  19. 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

  20. Influence of TCDD and natural Ah receptor agonists on benzo[a]pyrene-DNA adduct formation in the Caco-2 human colon cell line.

    PubMed

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

    2008-01-01

    Several compounds originating from cruciferous vegetables and citrus fruits bind to and activate the aryl hydrocarbon receptor (AhR). This receptor plays an important role in the toxicity of the known tumour promoter and potent AhR-agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, vegetables and fruits are generally considered as healthy. Therefore, besides the AhR activation, the natural AhR agonists (NAhRAs) are assumed to show other health-concerning effects. AhR activation induces several cytochrome P450 phase I enzymes involved, e.g. in the bioactivation of carcinogenic polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), and may as such stimulate DNA adduct formation of those compounds. Therefore, the influence of TCDD, indolo[3,2-b]carbazole (ICZ, an NAhRA originating from cruciferous vegetables) and an NAhRA-containing extract of grapefruit juice (GJE) on BaP-DNA adduct formation in the human Caco-2 cell line was studied. Also, we investigated if different effects of TCDD, ICZ and GJE on adduct formation could be related to the modulation of transcription of biotransformation- and DNA-repair enzymes. Co-exposure to high AhR-activating concentrations of both TCDD and ICZ significantly reduced the amount of BaP-DNA adducts at 0.1 microM BaP, while at higher concentrations of BaP no influence was observed. In contrast, exposure to 0.1 microM BaP combined with GJE showed a significant increase in BaP-DNA adducts, and a significant decrease at 0.3 and 1 microM BaP. These differences could not be related to transcription of the phase I and II enzymes CYP1A1, CYP1B1, NQO1, GSTP1 and UGT1A6 or to transcription of the nucleotide excision repair enzymes ERCC1, XPA, XPC, XPF and XPG. We conclude that ICZ showed a similar effect on BaP-DNA adduct formation than TCDD, while GJE influenced the adduct formation in a different way. The difference in the influence on adduct formation may be due to effects at the level of enzyme activity, rather than gene

  1. Detection of mild to moderate influenza A/H7N9 infection by China’s national sentinel surveillance system for influenza-like illness: case series

    PubMed Central

    Ip, Dennis KM; Liao, Qiaohong; Wu, Peng; Gao, Zhancheng; Cao, Bin; Feng, Luzhao; Xu, Xiaoling; Jiang, Hui; Li, Ming; Bao, Jing; Zheng, Jiandong; Zhang, Qian; Chang, Zhaorui; Li, Yu; Liu, Fengfeng; Ni, Michael Y; Wu, Joseph T; Cowling, Benjamin J; Yang, Weizhong

    2013-01-01

    Objective To characterise the complete case series of influenza A/H7N9 infections as of 27 May 2013, detected by China’s national sentinel surveillance system for influenza-like illness. Design Case series. Setting Outpatient clinics and emergency departments of 554 sentinel hospitals across 31 provinces in mainland China. Cases Infected individuals were identified through cross-referencing people who had laboratory confirmed A/H7N9 infection with people detected by the sentinel surveillance system for influenza-like illness, where patients meeting the World Health Organization’s definition of influenza-like illness undergo weekly surveillance, and 10-15 nasopharyngeal swabs are collected each week from a subset of patients with influenza-like illness in each hospital for virological testing. We extracted relevant epidemiological data from public health investigations by the Centers for Disease Control and Prevention at the local, provincial, and national level; and clinical and laboratory data from chart review. Main outcome measure Epidemiological, clinical, and laboratory profiles of the case series. Results Of 130 people with laboratory confirmed A/H7N9 infection as of 27 May 2013, five (4%) were detected through the sentinel surveillance system for influenza-like illness. Mean age was 13 years (range 2-26), and none had any underlying medical conditions. Exposure history, geographical location, and timing of symptom onset of these five patients were otherwise similar to the general cohort of laboratory confirmed cases so far. Only two of the five patients needed hospitalisation, and all five had mild or moderate disease with an uneventful course of recovery. Conclusion Our findings support the existence of a “clinical iceberg” phenomenon in influenza A/H7N9 infections, and reinforce the need for vigilance to the diverse presentation that can be associated with A/H7N9 infection. At the public health level, indirect evidence suggests a substantial

  2. 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

  3. Immunogenicity of a monovalent influenza A(H1N1)pdm09 vaccine in patients with hematological malignancies

    PubMed Central

    Ide, Yuichiro; Imamura, Yutaka; Ohfuji, Satoko; Fukushima, Wakaba; Ide, Saburo; Tsutsumi, Chiyo; Koga, Masahisa; Maeda, Kazuhiro; Hirota, Yoshio

    2014-01-01

    Patients with hematological malignancies have high risk for morbidity and mortality from influenza. This study was conducted to evaluate the immunogenicity and reactogenicity of an influenza A(H1N1)pdm09 vaccine among such subjects. Fifty subjects were vaccinated twice during the 2009–2010 season. The antibody response was expressed in terms of mean fold rise (MFR) of geometric mean titer, seroresponse proportion (sR), and seroprotection proportion (sP). The first vaccination induced only a small response, and additional antibody was acquired after the second dose (MFR 2.3 and 3.9, sR 32% and 54%, and sP 30% and 48% after the first and the second vaccination, respectively). Rituximab treatment showed an especially inhibitory effect (MFR 1.3, sR 9% and sP 0%). When analyzed using logistic regression models, only rituximab was found to have an independent effect; the adjusted odds ratio for sR was 0.09 (P = 0.05). Influenza vaccination of patients with hematological malignancies resulted in adepuate response, and the second vaccination induced additional antibody. It is therefore recommended to vaccinate this group twice. PMID:25424946

  4. Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes.

    PubMed

    Borza, Alexandra; Plöttner, Sabine; Wolf, Alexander; Behm, Claudia; Selinski, Silvia; Hengstler, Jan G; Roos, Peter H; Bolt, Hermann M; Kuhlmann, Jürgen; Föllmann, Wolfram

    2008-12-01

    Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes. PMID:18989657

  5. Microevolution of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Humans, Egypt, 2007–2011

    PubMed Central

    Younan, Mary; Poh, Mee Kian; Elassal, Emad; Davis, Todd; Rivailler, Pierre; Balish, Amanda L.; Simpson, Natosha; Jones, Joyce; Deyde, Varough; Loughlin, Rosette; Perry, Ije; Gubareva, Larisa; ElBadry, Maha A.; Truelove, Shaun; Gaynor, Anne M.; Mohareb, Emad; Amin, Magdy; Cornelius, Claire; Pimentel, Guillermo; Earhart, Kenneth; Naguib, Amel; Abdelghani, Ahmed S.; Refaey, Samir; Klimov, Alexander I.; Kandeel, Amr

    2013-01-01

    We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007–2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. PMID:23260983

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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. PMID:24534766

  16. Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London.

    PubMed

    Birrell, Paul J; Ketsetzis, Georgios; Gay, Nigel J; Cooper, Ben S; Presanis, Anne M; Harris, Ross J; Charlett, André; Zhang, Xu-Sheng; White, Peter J; Pebody, Richard G; De Angelis, Daniela

    2011-11-01

    The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution. PMID:22042838

  17. Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London

    PubMed Central

    Birrell, Paul J.; Ketsetzis, Georgios; Gay, Nigel J.; Cooper, Ben S.; Presanis, Anne M.; Harris, Ross J.; Charlett, André; Zhang, Xu-Sheng; White, Peter J.; Pebody, Richard G.; De Angelis, Daniela

    2011-01-01

    The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a Bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution. PMID:22042838

  18. Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic.

    PubMed

    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

  19. 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

  20. [Pandemic influenza A(H1N1): the experience of the Spanish Laboratories of Influenza Network (ReLEG)].

    PubMed

    Cuevas González-Nicolás, María Teresa; Ledesma Moreno, Juan; Pozo Sánchez, Francisco; Casas Flecha, Inmaculada; Pérez-Breña, Pilar

    2010-01-01

    There are three types of influenza viruses: A, B, C. These viruses evolves constantly due to two main characteristics: the first one is the lack of the correction ability of the viral polymerase which causes the accumulation of single nucleotide mutations in the viral genes introduced by an error-prone viral RNA polymerase, (antigenic shift). The second one is the nature of their genome, formed by eight segments, which allows the interchange of genes between two different viral strains (antigenic drift). This viral plasticity, has allowed to the influenza A viruses to infect new host species and to cause infections with a pandemic characteristics. The Spanish influenza surveillance system, SVGE (its Spanish acronym), arises as a response to the possibility of facing a pandemic situation, especially after the transmission of avian influenza viruses to humans. This surveillance system is formed by sixteen physician and paediatrics network, nineteen epidemiological services coordinated by the National Epidemiological Centre (CNE) and eighteen laboratories , the Spanish Laboratories of Influenza network (ReLEG), coordinated by the National Centre of Microbiology. The aim of this article is to show the action of the ReLEG, in the pandemic caused by the influenza virus A(H1N1) during the season 2009-2010. The main objective of this network is the surveillance of the circulating viruses by means of their detection and their subsequent antigenic and genetic characterization, including the detection of resistance mutations against the main drugs, such as Oseltamivir. PMID:21203714

  1. Algebraic analysis of social networks for bio-surveillance: the cases of SARS-Beijing-2003 and AH1N1 influenza-México-2009.

    PubMed

    Hincapié, Doracelly; Ospina, Juan

    2011-01-01

    Algebraic analysis of social networks exhibited by SARS-Beijing-2003 and AH1N1 flu-México-2009 was realized. The main tools were the Tutte polynomials and Maple package Graph-Theory. The topological structures like graphs and networks were represented by invariant polynomials. The evolution of a given social network was represented like an evolution of the algebraic complexity of the corresponding Tutte polynomial. The reduction of a given social network was described like an involution of the algebraic complexity of the associated Tutte polynomial. The outbreaks of SARS and AH1N1 Flu were considered like represented by a reduction of previously existing contact networks via the control measures executed by health authorities. From Tutte polynomials were derived numerical indicators about efficiency of control measures. PMID:21431617

  2. Early detection of influenza A(H5) viruses with affinity for the human sialic acid receptor by MALDI-TOF mass spectrometry based mutation detection.

    PubMed

    Yea, C; McCorrister, S; Westmacott, G; Petric, M; Tellier, R

    2011-03-01

    Highly pathogenic avian influenza (HPAI) A(H5N1) strains have been causing sporadic cases of disease in South East Asia and Africa for many years. These cases are associated with a high fatality rate, and it is feared that the virus could evolve into a strain capable of causing a pandemic. It is likely that a requirement for a A(H5) pandemic to occur is a switch in the receptor affinity of the virus. Candidate mutations in the hemagglutinin glycoprotein have been identified in the literature, and their emergence in circulating viruses would be an ominous development. This study describes a method to identify the presence of these mutations, even within a quasispecies, using RT-PCR followed by in vitro translation and peptide characterization by MALDI-TOF mass spectrometry. PMID:21195111

  3. 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.

  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. PMID:27410735

  5. 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.

  6. Reconstruction of the Evolutionary Dynamics of A(H3N2) Influenza Viruses Circulating in Italy from 2004 to 2012

    PubMed Central

    Ebranati, Erika; Gozalo-Margüello, Monica; Veo, Carla; Bubba, Laura; Amendola, Antonella; Ciccozzi, Massimo; Galli, Massimo; Zanetti, Alessandro Remo; Baldanti, Fausto; Zehender, Gianguglielmo

    2015-01-01

    Background Influenza A viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (HA) domain causes seasonal epidemics. The A(H3N2) virus has higher mutation rate than the A(H1N1) virus. The aim of this study was to reconstruct the evolutionary dynamics of the A(H3N2) viruses circulating in Italy between 2004 and 2012 in the light of the forces driving viral evolution. Methods Phylodinamic analyses were made using a Bayesian method, and codon-specific positive selection acting on the HA coding sequence was evaluated. Results Global and local phylogenetic analyses showed that the Italian strains collected between 2004 and 2012 grouped into five significant Italian clades that included viral sequences circulating in different epidemic seasons. The time of the most recent common ancestor (tMRCA) of the tree root was between May and December 2003. The tMRCA estimates of the major clades suggest that the origin of a new viral strain precedes the effective circulation of the strain in the Italian population by 6–31 months, thus supporting a central role of global migration in seeding the epidemics in Italy. The study of selection pressure showed that four codons were under positive selection, three of which were located in antigenic sites. Analysis of population dynamics showed the alternation of periods of exponential growth followed by a decrease in the effective number of infections corresponding to epidemic and inter-epidemic seasons. Conclusions Our analyses suggest that a complex interaction between the immune status of the population, migrations, and a few selective sweeps drive the influenza A(H3N2) virus evolution. Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation. PMID:26331945

  7. 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

  8. 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. PMID:26921801

  9. 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

  10. Risk factors for mortality among 2009 A/H1N1 influenza hospitalizations in Maricopa County, Arizona, April 2009 to March 2010.

    PubMed

    Chowell, G; Ayala, A; Berisha, V; Viboud, C; Schumacher, M

    2012-01-01

    We analyzed individual-level data on pandemic influenza A/H1N1pdm hospitalizations from the enhanced surveillance system of the Maricopa County Department of Public Health, AZ, USA from April 1st, 2009 to March 31st, 2010. We also assessed the the risk of death among A/H1N1 hospitalizations using multivariate logistic regression. Hospitalization rates were significantly higher among Native Americans (risk ratio (RR)  =  6.2; 95% CI: 6.15, 6.21), non-Hispanic Black (RR = 3.84; 95% CI: 3.8, 3.9), and Hispanics (RR = 2.0; 95% CI: 2.0, 2.01) compared to non-Hispanic Whites. Throughout the spring, 59.2% of hospitalized patients received antiviral treatment; the proportion of patients treated increased significantly during the fall to 74.4% (Chi-square test, P < 0.0001). In our best-fit logistic model, the adjusted risk of death among A/H1N1 inpatients was significantly higher during the fall wave (August 16, 2009 to March 31, 2010, OR = 3.94; 95% CI: 1.72, 9.03) compared to the spring wave (April 1, 2009 to August 15, 2009). Moreover, chronic lung disease (OR = 3.5; 95% CI: 1.7, 7.4), cancer within the last 12 months (OR = 4.3; 95%CI: 1.3, 14.8), immuno-suppression (OR = 4.0; 95% CI: 1.84, 8.9), and admission delays (OR = 4.6; 95% CI: 2.2, 9.5) were significantly associated with an increased the risk of death among A/H1N1 inpatients. PMID:22844347

  11. Detection of 2009 pandemic influenza A(H1N1) virus Infection in different age groups by using rapid influenza diagnostic tests

    PubMed Central

    Gao, Fengxiang; Loring, Carol; Laviolette, Michael; Bolton, Denise; Daly, Elizabeth R.; Bean, Christine

    2011-01-01

    Please cite this paper as: Gao et al. (2011) Detection of 2009 pandemic influenza A(H1N1) virus Infection in different age groups by using rapid influenza diagnostic tests. Influenza and Other Respiratory Viruses 6(3), e30–e34. Background  The performance of rapid influenza diagnostic tests (RIDTs) in detecting influenza A(H1N1) 2009 has varied widely. Evaluations of RIDTs among infected individuals across all age groups have not been described in depth. Objectives  Determine RIDT clinical sensitivity in comparison with influenza detection using real‐time RT‐PCR among patients infected with influenza A(H1N1) 2009 across all age groups. Study design  This study analyzed respiratory specimens received by the New Hampshire Public Health Laboratories (NHPHL) from September 1, 2009, through December 31, 2009. RIDT performance was evaluated among different age groups of patients determined to be infected with influenza A (H1N1) 2009, and the association between age and RIDT sensitivity was determined. Results  Of 1373 specimens examined, 269 tested positive for influenza A(H1N1) 2009 by real‐time RT‐PCR (rRT‐PCR) and had RIDT results available. Overall clinical sensitivity and specificity of RIDTs were 53·9 and 98·5%, respectively. By age group, clinical sensitivity was 85·7% in patients <2 years old, 60·3% in patients between 2‐ and 39 years old, and 33·3% in patients aged 40 and older. Logistic regression analysis indicated that increasing age was negatively associated with RIDT performance. Conclusion  Rapid influenza diagnostic test sensitivity decreased significantly with increasing age. Findings from this study may impact a clinician’s interpretation of RIDT test results and ultimately have implications in clinical decision‐making. PMID:22114876

  12. Bond strength to root dentin and fluid filtration test of AH Plus/gutta-percha, EndoREZ and RealSeal systems

    PubMed Central

    MAHDI, Alaa Abdul; BOLAÑOS-CARMONA, Victoria; GONZALEZ-LOPEZ, Santiago

    2013-01-01

    Objectives To investigate the bond strength and seal ability produced by AH Plus/gutta-percha, EndoREZ and RealSeal systems to root canal dentin. Material and Methods Sixty extracted single-root human teeth, instrumented manually to size 40, were divided into three groups (n=20) according to the sealer used; G1: AH Plus, G2: EndoREZ, and G3: RealSeal sealers. After filling using the lateral condensation technique, each sealer group was randomly divided into two subgroups according to the tests applied (n=10 for µPush-out test and n=10 for fluid filtration test). A fluid filtration method was used for quantitative evaluation of apical leakage. Four 1-mm-thick slices (cervical and medium level) were obtained from each root sample and a µPush-out test was performed. Failure modes were examined under microscopy at 40x, and a one-way ANOVA was applied to analyze the permeability. Non-parametrical statistics for related (Friedman's and Wilcoxon's rank tests) or unrelated samples (Kruskal-Wallis' and Mann-Whitney's tests) allowed for comparisons of µPush-out strength values among materials at the different levels. Statistical significance was accepted for p values <.05. Results There are no significant differences among fluid filtration of the three sealers. The sealer/core material does not significantly influence the µPush-out bond strength values (F=2.49; p=0.10), although statistically significant differences were detected with regard to root level (Chi2=23.93; p<0.001). AH Plus and RealSeal obtained higher bond strength to intraradicular dentin in the medium root slices. Conclusions There are no significant differences between the permeability and global µPush-out bond strength to root canal dentin achieved by AH Plus/gutta-percha, EndoREZ and RealSeal systems. PMID:24037078

  13. 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.

  14. 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.

  15. Impact of AhR, CYP1A1 and GSTM1 genetic polymorphisms on TP53 R273G mutations in individuals exposed to polycyclic aromatic hydrocarbons.

    PubMed

    Gao, Meili; Li, Yongfei; Xue, Xiaochang; Long, Jiangang; Chen, Lan; Shah, Walayat; Kong, Yu

    2014-01-01

    This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers. PMID:24761888

  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. Characterization of Quasispecies of Pandemic 2009 Influenza A Virus (A/H1N1/2009) by De Novo Sequencing Using a Next-Generation DNA Sequencer

    PubMed Central

    Kuroda, Makoto; Katano, Harutaka; Nakajima, Noriko; Tobiume, Minoru; Ainai, Akira; Sekizuka, Tsuyoshi; Hasegawa, Hideki; Tashiro, Masato; Sasaki, Yuko; Arakawa, Yoshichika; Hata, Satoru; Watanabe, Masahide; Sata, Tetsutaro

    2010-01-01

    Pandemic 2009 influenza A virus (A/H1N1/2009) has emerged globally. In this study, we performed a comprehensive detection of potential pathogens by de novo sequencing using a next-generation DNA sequencer on total RNAs extracted from an autopsy lung of a patient who died of viral pneumonia with A/H1N1/2009. Among a total of 9.4×106 40-mer short reads, more than 98% appeared to be human, while 0.85% were identified as A/H1N1/2009 (A/Nagano/RC1-L/2009(H1N1)). Suspected bacterial reads such as Streptococcus pneumoniae and other oral bacteria flora were very low at 0.005%, and a significant bacterial infection was not histologically observed. De novo assembly and read mapping analysis of A/Nagano/RC1-L/2009(H1N1) showed more than ×200 coverage on average, and revealed nucleotide heterogeneity on hemagglutinin as quasispecies, specifically at two amino acids (Gly172Glu and Gly239Asn of HA) located on the Sa and Ca2 antigenic sites, respectively. Gly239 and Asn239 on antigenic site Ca2 appeared to be minor amino acids compared with the highly distributed Asp239 in H1N1 HAs. This study demonstrated that de novo sequencing can comprehensively detect pathogens, and such in-depth investigation facilitates the identification of influenza A viral heterogeneity. To better characterize the A/H1N1/2009 virus, unbiased comprehensive techniques will be indispensable for the primary investigations of emerging infectious diseases. PMID:20428231

  18. Risk Factors for Mortality among 2009 A/H1N1 Influenza Hospitalizations in Maricopa County, Arizona, April 2009 to March 2010

    PubMed Central

    Chowell, G.; Ayala, A.; Berisha, V.; Viboud, C.; Schumacher, M.

    2012-01-01

    We analyzed individual-level data on pandemic influenza A/H1N1pdm hospitalizations from the enhanced surveillance system of the Maricopa County Department of Public Health, AZ, USA from April 1st, 2009 to March 31st, 2010. We also assessed the the risk of death among A/H1N1 hospitalizations using multivariate logistic regression. Hospitalization rates were significantly higher among Native Americans (risk ratio (RR)  =  6.2; 95% CI: 6.15, 6.21), non-Hispanic Black (RR = 3.84; 95% CI: 3.8, 3.9), and Hispanics (RR = 2.0; 95% CI: 2.0, 2.01) compared to non-Hispanic Whites. Throughout the spring, 59.2% of hospitalized patients received antiviral treatment; the proportion of patients treated increased significantly during the fall to 74.4% (Chi-square test, P < 0.0001). In our best-fit logistic model, the adjusted risk of death among A/H1N1 inpatients was significantly higher during the fall wave (August 16, 2009 to March 31, 2010, OR = 3.94; 95% CI: 1.72, 9.03) compared to the spring wave (April 1, 2009 to August 15, 2009). Moreover, chronic lung disease (OR = 3.5; 95% CI: 1.7, 7.4), cancer within the last 12 months (OR = 4.3; 95%CI: 1.3, 14.8), immuno-suppression (OR = 4.0; 95% CI: 1.84, 8.9), and admission delays (OR = 4.6; 95% CI: 2.2, 9.5) were significantly associated with an increased the risk of death among A/H1N1 inpatients. PMID:22844347

  19. An in vitro study of apical and coronal microleakage of laterally condensed gutta percha with Ketac-Endo and AH-26.

    PubMed

    Oliver, C M; Abbott, P V

    1998-08-01

    The purpose of this in vitro study was to compare both apical and coronal dye penetration when Ketac-Endo and AH-26 sealers were used with laterally condensed gutta percha. Crowns were removed from 28 teeth and the root canals were biomechanically prepared. The teeth were divided into two groups of 12-teeth each and a control group of 4 teeth. Root canals in the two experimental groups were filled with laterally condensed gutta percha and either Ketac-Endo or AH-26 sealer. The Ketac-Endo group had the coronal 3 mm of gutta percha and sealer removed and the resultant cavity was filled with Ketac-Endo alone. After the sealers had set, the root surfaces were coated with nail varnish except at the apex and at the coronal end. Positive controls had no root fillings and were coated with nail varnish in the same manner while the negative controls were sealed apically and coronally with Cavit prior to sealing the entire external root surface with nail varnish. Specimens were placed in 2% methylene blue dye in a vacuum of 660 mm of mercury for five minutes and then left immersed for a further two days. The roots were vertically sectioned to determine the following mean levels of dye penetration: Ketac-Endo, 1.08 mm apically and 6.29 mm coronally; AH-26, 0.75 mm apically and 6.67 mm coronally. Positive controls had total leakage and negative controls had no leakage. This study demonstrated that the apical and coronal seals obtained with Ketac-Endo and AH-26 were not significantly different although the apical seal obtained with each material was significantly better than the corresponding coronal seal. PMID:9775474

  20. Effectiveness of pandemic and seasonal influenza vaccine in preventing pandemic influenza A(H1N1)2009 infection in England and Scotland 2009-2010.

    PubMed

    Hardelid, P; Fleming, D M; McMenamin, J; Andrews, N; Robertson, C; SebastianPillai, P; Ellis, J; Carman, W; Wreghitt, T; Watson, J M; Pebody, R G

    2011-01-01

    Following the global spread of pandemic influenza A(H1N1)2009, several pandemic vaccines have been rapidly developed. The United Kingdom and many other countries in the northern hemisphere implemented seasonal and pandemic influenza vaccine programmes in October 2009. We present the results of a case–control study to estimate effectiveness of such vaccines in preventing confirmed pandemic influenza infection. Some 5,982 individuals with influenza-like illness seen in general practices between November 2009 and January 2010 were enrolled. Those testing positive on PCR for pandemic influenza were assigned as cases and those testing negative as controls. Vaccine effectiveness was estimated as the relative reduction in odds of confirmed infection between vaccinated and unvaccinated individuals. Fourteen or more days after immunisation with the pandemic vaccine, adjusted vaccine effectiveness (VE) was 72% (95% confidence interval (CI): 21% to 90%). If protection was assumed to start after seven or more days, the adjusted VE was 71% (95% CI: 37% to 87%). Pandemic influenza vaccine was highly effective in preventing confirmed infection with pandemic influenza A(H1N1)2009 from one week after vaccination. No evidence of effectiveness against pandemic influenza A(H1N1)2009 was found for the 2009/10 trivalent seasonal influenza vaccine (adjusted VE of -30% (95% CI: -89% to 11%)). PMID:21251487

  1. Precursor systems analyses of automated highway systems. Commercial and transit AHS analysis. Volume 7. Final report, 9 September 1993-30 October 1994

    SciTech Connect

    1995-05-01

    The program described by the 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 AHS effort was conducted by a team formed and directed by the Calspan Advanced Technology Center. Primary Team members included Calspan, Parsons Brinckerhoff, Dunn Engineering Associates, and Princeton University. Supporting members of the team were BMW, New York Thruway Authority, New York State Department of Transportation, Massachusetts Department of Transportation, the New Jersey Department of Transportation, Boston Research, Vitro Corporation, and Michael P. Walsh of Walsh Associates. The 17 task reports (A through P plus Representative Systems Configurations) are organized into 8 volumes. This volume describes Commercial and Transit AHS Analysis (Task F.) This task was performed as two independent and parallel efforts. Parsons Brinckerhoff performed the work reported in the main body of the report and Appendix A. That work was supervised by Marvin Gersten and supported by Jeanine Jankowski, both of Parsons Brinckerhoff. A separate and parallel analysis, performed by Prinecton University, appears as Appendix B (with its own Executive Summary). The work was developed by Alain Kornhauser.

  2. The nuclear magnetic resonance solution structure of the synthetic AhPDF1.1b plant defensin evidences the structural feature within the γ-motif.

    PubMed

    Meindre, Fanny; Lelièvre, Dominique; Loth, Karine; Mith, Oriane; Aucagne, Vincent; Berthomieu, Pierre; Marquès, Laurence; Delmas, Agnès F; Landon, Céline; Paquet, Françoise

    2014-12-16

    Plant defensins (PDF) are cysteine-rich peptides that are major actors in the innate immunity in plants. Besides their antifungal activity, some PDF such as Arabidopsis halleri PDF1.1b confer zinc tolerance in plants. Here we present (i) an efficient protocol for the production of AhPDF1.1b by solid-phase peptide synthesis followed by controlled oxidative folding to obtain the highly pure native form of the defensin and (ii) the three-dimensional (3D) nuclear magnetic resonance structure of AhPDF1.1b, the first 3D structure of plant defensin obtained with a synthetic peptide. Its fold is organized around the typical cysteine-stabilized α-helix β-sheet motif and contains the γ-core motif involved in the antifungal activity of all plant defensins. On the basis of our structural analysis of AhPDF1 defensins combined with previous biological data for antifungal and zinc tolerance activities, we established the essential role of cis-Pro41 within the γ-core. In fact, the four consecutive residues (Val39-Phe40-Pro41-Ala42) are strictly conserved for plant defensins able to tolerate zinc. We hypothesized that structural and/or dynamic features of this sequence are related to the ability of the defensin to chelate zinc. PMID:25419866

  3. Gibberella moniliformis AH13 with antitumor activity, an endophytic fungus strain producing triolein isolated from Adlay (Coix lacryma-jobi: poaceae).

    PubMed

    Jia, Min; Ming, Qian-Liang; Zhang, Qiao-Yan; Chen, Yu; Cheng, Nuo; Wu, Wen-wen; Han, Ting; Qin, Lu-Ping

    2014-09-01

    In this study, the isolation of an endophytic fungus from the leaves of the medicinal herb adlay (Coix lacryma-jobi L. var. ma-yuen Stapf) is reported for the first time. The fungus produced Triolein (trioleoylglycerol), a major constituent of triacylglycerols (TAGs) of adlay, in rice medium under shake-flask and bench-scale fermentation conditions. The fungus was identified as Gibberella moniliformis (Fusarium verticillioides) by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Triolein was identified by HPLC-ELSD coupled with APCI-MS and confirmed through comparison with authentic standard. The concentration of triolein produced by G. moniliformis AH13 reached 2.536 ± 0.006 mg/g dry weight of mycelium. Moreover, the EtOAc extract of G. moniliformis AH13 showed strong antitumor activity against four types of tumor cells (A549, HCT116, MDA-MB-231, and SW1990). These results suggest that G. moniliformis AH13 in adlay has significant scientific and industrial potential to meet the pharmaceutical demands and sustainable energy requirements for TAGs in a cost-effective, easily accessible, and reproducible way and is also a potential novel source of natural antitumor bioactive agents. PMID:24810291

  4. 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. PMID:24146347

  5. Angiogenic and inflammatory markers in acute respiratory distress syndrome and renal injury associated to A/H1N1 virus infection.

    PubMed

    Bautista, Edgar; Arcos, Magali; Jimenez-Alvarez, Luís; García-Sancho, Ma Cecilia; Vázquez, María E; Peña, Erika; Higuera, Anjarath; Ramírez, Gustavo; Fernández-Plata, Rosario; Cruz-Lagunas, Alfredo; García-Moreno, Sara A; Urrea, Francisco; Ramírez, Remedios; Correa-Rotter, Ricardo; Pérez-Padilla, José Rogelio; Zúñiga, Joaquín

    2013-06-01

    Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death. PMID:23542734

  6. Detection of oseltamivir-resistant pandemic influenza A(H1N1)pdm2009 in Brazil: can community transmission be ruled out?

    PubMed

    Souza, Thiago Moreno L; Resende, Paola C; Fintelman-Rodrigues, Natalia; Gregianini, Tatiana Schaffer; Ikuta, Nilo; Fernandes, Sandra Bianchini; Cury, Ana Luisa Furtado; Rosa, Maria do Carmo Debur; Siqueira, Marilda M

    2013-01-01

    Although surveillance efforts that monitor the emergence of drug-resistant strains of influenza are critical, systematic analysis is overlooked in most developing countries. We report on the occurrence of strains of pandemic influenza A(H1N1)pdm09 with resistance and decreased susceptibility to oseltamivir (OST) in Brazil in 2009, 2011 and 2012. We found 7 mutant viruses, 2 with the mutation S247N and other 5 with the mutation H275Y. Most of these viruses were from samples concentrated in the southern region of Brazil. Some of these resistant viruses were detected prior to the initiation of OST treatment, suggesting that community transmission of mutant viruses may exist. Moreover, we show that one of these OST-resistant (H275Y) strains of A(H1N1)pdm09 was discovered in the tri-border region between Brazil, Argentina and Paraguay, highlighting that this strain could also be found in other Latin American countries. Our findings reinforce the importance of enhanced antiviral resistance surveillance in Brazil and in other Latin American countries to confirm or rule out the community transmission of OST-resistant strains of A(H1N1)pdm09. PMID:24244615

  7. Evaluation of immediate and delayed post space preparation on sealing ability of Resilon–Epiphany and Gutta percha-AH plus sealer

    PubMed Central

    Dhaded, Neha; Uppin, Veerendra M.; Dhaded, Sunil; Patil, Chetan

    2013-01-01

    Aim: To evaluate the influence of immediate and delayed post space preparation on sealing ability of Resilon-Epiphany and Gutta percha-AH plus. Materials and Methods: Eighty extracted permanent maxillary central and lateral incisors were decoronated. Roots canals were prepared and obturated. Samples were divided into four groups depending on the time of post space preparation and obturated material. Group I and II: Immediate and delayed post space preparation respectively with Gutta percha/AH plus as obturating material. Group III and IV: Immediate and delayed post space preparation with Resilon/Epiphany as the obturating material. The samples were kept in methylene blue dye, sectioned and then measured under stereomicroscope and studied under SEM. Statistical Analysis: The data was subjected to statistical analysis using unpaired t-test. Results: There was significant difference found between immediate and delayed post space preparation in Resilon-Epiphany group (P = 0.0109) as well as in AH plus-GP group (<0.0001). Difference in the sealing ability of the two materials was seen in delayed group (P = 0.0202). No statistically significant result was found between the two obturating materials when post space was prepared immediately (P = 0.0875). Conclusion: Within the limitations of this study, there was significantly less leakage when post space is prepared immediately in both the groups. Resilon-Epiphany shows better results when post space is delayed amongst the two whereas in immediate post space preparation there is no significant difference. PMID:24347884

  8. Enhanced Mammalian Transmissibility of Seasonal Influenza A/H1N1 Viruses Encoding an Oseltamivir-Resistant Neuraminidase

    PubMed Central

    Rahmat, Saad; Pica, Natalie

    2012-01-01

    Between 2007 and 2009, oseltamivir resistance developed among seasonal influenza A/H1N1 (sH1N1) virus isolates at an exponential rate, without a corresponding increase in oseltamivir usage. We hypothesized that the oseltamivir-resistant neuraminidase (NA), in addition to being relatively insusceptible to the antiviral effect of oseltamivir, might confer an additional fitness advantage on these viruses by enhancing their transmission efficiency among humans. Here we demonstrate that an oseltamivir-resistant clinical isolate, an A/Brisbane/59/2007(H1N1)-like virus isolated in New York State in 2008, transmits more efficiently among guinea pigs than does a highly similar, contemporaneous oseltamivir-sensitive isolate. With reverse genetics reassortants and point mutants of the two clinical isolates, we further show that expression of the oseltamivir-resistant NA in the context of viral proteins from the oseltamivir-sensitive virus (a 7:1 reassortant) is sufficient to enhance transmissibility. In the guinea pig model, the NA is the critical determinant of transmission efficiency between oseltamivir-sensitive and -resistant Brisbane/59-like sH1N1 viruses, independent of concurrent drift mutations that occurred in other gene products. Our data suggest that the oseltamivir-resistant NA (specifically, one or both of the companion mutations, H275Y and D354G) may have allowed resistant Brisbane/59-like viruses to outtransmit sensitive isolates. These data provide in vivo evidence of an evolutionary mechanism that would explain the rapidity with which oseltamivir resistance achieved fixation among sH1N1 isolates in the human reservoir. PMID:22532693

  9. Seasonality of Influenza A(H7N9) Virus in China—Fitting Simple Epidemic Models to Human Cases

    PubMed Central

    Lin, Qianying; Lin, Zhigui; Chiu, Alice P. Y.; He, Daihai

    2016-01-01

    Background Three epidemic waves of influenza A(H7N9) (hereafter ‘H7N9’) human cases have occurred between March 2013 and July 2015 in China. However, the underlying transmission mechanism remains unclear. Our main objective is to use mathematical models to study how seasonality, secular changes and environmental transmission play a role in the spread of H7N9 in China. Methods Data on human cases and chicken cases of H7N9 infection were downloaded from the EMPRES-i Global Animal Disease Information System. We modelled on chicken-to-chicken transmission, assuming a constant ratio of 10−6 human case per chicken case, and compared the model fit with the observed human cases. We developed three different modified Susceptible-Exposed-Infectious-Recovered-Susceptible models: (i) a non-periodic transmission rate model with an environmental class, (ii) a non-periodic transmission rate model without an environmental class, and (iii) a periodic transmission rate model with an environmental class. We then estimated the key epidemiological parameters and compared the model fit using Akaike Information Criterion and Bayesian Information Criterion. Results Our results showed that a non-periodic transmission rate model with an environmental class provided the best model fit to the observed human cases in China during the study period. The estimated parameter values were within biologically plausible ranges. Conclusions This study highlighted the importance of considering secular changes and environmental transmission in the modelling of human H7N9 cases. Secular changes were most likely due to control measures such as Live Poultry Markets closures that were implemented during the initial phase of the outbreaks in China. Our results suggested that environmental transmission via viral shedding of infected chickens had contributed to the spread of H7N9 human cases in China. PMID:26963937

  10. Tumor growth inhibition and nutritional effect of D-amino acid solution in AH109A hepatoma-bearing rats.

    PubMed

    Sasamura, T; Matsuda, A; Kokuba, Y

    1998-02-01

    We examined the inhibitional and nutritional effects of total parenteral nutrition (TPN) containing D-amino acids (D-phenylalanine, D-Phe; D-valine, D-Val; D-leucine, D-Leu; D-methionine, D-Met) on tumor growth in AH109A hepatoma-bearing rats. Five experimental groups were examined: a control amino acid solution group (control group), D-Phe group, D-Val group, D-Leu group and D-Met group. The analysis of tumor volume and weight revealed significant tumor growth inhibition in the D-Val group as compared with the control group. In the D-Val group, decreases of DNA and protein contents in the tumor tissues were also observed. The D-Leu and D-Met groups showed a tendency toward tumor growth inhibition. The protein content in the liver tissues of these two groups was significantly higher as compared with the control group. The DNA content in the liver tissue was also significantly higher in the D-Met group. The body weight including the tumor (on the final day of TPN) was significantly lower in the D-Val group as compared with the control group, but there was no significant difference in the groups for body weights not including tumors (carcass body weight). The hematocrit and hemoglobin values, indicators of anemia, were significantly higher in the D-Val group as compared with the control group. From these results, regarding tumor growth inhibition, the D-Val solution had the strongest inhibitory effect with no negative influence on the host, and improvement of nutritional status was also suggested in the rats that received the D-Leu or D-Met solutions. PMID:9591236

  11. Long Term Immune Responses to Pandemic Influenza A/H1N1 Infection in Solid Organ Transplant Recipients

    PubMed Central

    Baluch, Aliyah; Humar, Atul; Egli, Adrian; Gubbay, Jonathan; Lisboa, Luiz; Wilson, Leticia; Kumar, Deepali

    2011-01-01

    In solid organ transplant (SOT) recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1) resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI) testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8–15.4) after infection. After excluding those with cross-reactive antibody, 7/19 (36.8%) patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50%) and 8/22 (36.4%) patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection. PMID:22194870

  12. Spatial Modeling of Wild Bird Risk Factors for Highly Pathogenic A(H5N1) Avian Influenza Virus Transmission.

    PubMed

    Prosser, Diann J; Hungerford, Laura L; Erwin, R Michael; Ottinger, Mary Ann; Takekawa, John Y; Newman, Scott H; Xiao, Xiangming; Ellis, Erle C

    2016-05-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 yr, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae) are reported as secondary transmitters of HPAIV and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using geographic information software and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values and then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 to 30 km resolution for multiscale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications. PMID:27309075

  13. Seasonal Oscillation of Human Infection with Influenza A/H5N1 in Egypt and Indonesia

    PubMed Central

    Murray, Eleanor J.; Morse, Stephen S.

    2011-01-01

    As of June 22, 2011, influenza A/H5N1 has caused a reported 329 deaths and 562 cases in humans, typically attributed to contact with infected poultry. Influenza H5N1 has been described as seasonal. Although several studies have evaluated environmental risk factors for H5N1 in poultry, none have considered seasonality of H5N1 in humans. In addition, temperature and humidity are suspected to drive influenza in temperate regions, but drivers in the tropics are unknown, for H5N1 as well as other influenza viruses. An analysis was conducted to determine whether human H5N1 cases occur seasonally in association with changes in temperature, precipitation and humidity. Data analyzed were H5N1 human cases in Indonesia (n = 135) and Egypt (n = 50), from January 1, 2005 (Indonesia) or 2006 (Egypt) through May 1, 2008 obtained from WHO case reports, and average daily weather conditions obtained from NOAA's National Climatic Data Center. Fourier time series analysis was used to determine seasonality of cases and associations between weather conditions and human H5N1 incidence. Human H5N1 cases in Indonesia occurred with a period of 1.67 years/cycle (p<0.05) and in Egypt, a period of 1.18 years/cycle (p≅0.10). Human H5N1 incidence in Egypt, but not Indonesia, was strongly associated with meteorological variables (κ2≥0.94) and peaked in Egypt when precipitation was low, and temperature, absolute humidity and relative humidity were moderate compared to the average daily conditions in Egypt. Weather conditions coinciding with peak human H5N1 incidence in Egypt suggest that human infection may be occurring primarily via droplet transmission from close contact with infected poultry. PMID:21909409

  14. Purification and biochemical characterization of two detergent-stable serine alkaline proteases from Streptomyces sp. strain AH4.

    PubMed

    Touioui, Souraya Boulkour; Jaouadi, Nadia Zaraî; Boudjella, Hadjira; Ferradji, Fatma Zohra; Belhoul, Mouna; Rekik, Hatem; Badis, Abdelmalek; Bejar, Samir; Jaouadi, Bassem

    2015-07-01

    Streptomyces sp. strain AH4 exhibited a high ability to produce two extracellular proteases when cultured on a yeast malt-extract (ISP2)-casein-based medium. Pure proteins were obtained after heat treatment (30 min at 70 °C) and ammonium sulphate fractionation (30-60 %), followed by size exclusion HPLC column. Matrix assisted laser desorption ionization-time of flight mass spectrometry analysis revealed that the purified enzymes (named SAPS-P1 and SAPS-P2) were monomers with molecular masses of 36,417.13 and 21,099.10 Da, respectively. Their identified N-terminal amino acid displayed high homologies with those of Streptomyces proteases. While SAPS-P1 was optimally active at pH 12.0 and 70 °C, SAPS-P2 showed optimum activity at pH 10.0 and 60 °C. Both enzymes were completely stable within a wide range of temperature (45-75 °C) and pH (8.0-11.5). They were noted to be completely inhibited by phenylmethanesulfonyl fluoride and diisopropyl fluorophosphates, which confirmed their belonging to the serine proteases family. Compared to SAPS-P2, SAPS-P1 showed high thermostability and excellent stability towards bleaching, denaturing, and oxidizing agents. Both enzymes displayed marked stability and compatibility with a wide range of commercial laundry detergents and significant catalytic efficiencies compared to Subtilisin Carlsberg and Protease SG-XIV. Overall, the results indicated that SAPS-P1 and SAPS-P2 can be considered as potential promising candidates for future application as bioadditives in detergent formulations. PMID:26002109

  15. Estimating the life course of influenza A(H3N2) antibody responses from cross-sectional data.

    PubMed

    Kucharski, Adam J; Lessler, Justin; Read, Jonathan M; Zhu, Huachen; Jiang, Chao Qiang; Guan, Yi; Cummings, Derek A T; Riley, Steven

    2015-03-01

    The immunity of a host population against specific influenza A strains can influence a number of important biological processes, from the emergence of new virus strains to the effectiveness of vaccination programmes. However, the development of an individual's long-lived antibody response to influenza A over the course of a lifetime remains poorly understood. Accurately describing this immunological process requires a fundamental understanding of how the mechanisms of boosting and cross-reactivity respond to repeated infections. Establishing the contribution of such mechanisms to antibody titres remains challenging because the aggregate effect of immune responses over a lifetime are rarely observed directly. To uncover the aggregate effect of multiple influenza infections, we developed a mechanistic model capturing both past infections and subsequent antibody responses. We estimated parameters of the model using cross-sectional antibody titres to nine different strains spanning 40 years of circulation of influenza A(H3N2) in southern China. We found that "antigenic seniority" and quickly decaying cross-reactivity were important components of the immune response, suggesting that the order in which individuals were infected with influenza strains shaped observed neutralisation titres to a particular virus. We also obtained estimates of the frequency and age distribution of influenza infection, which indicate that although infections became less frequent as individuals progressed through childhood and young adulthood, they occurred at similar rates for individuals above age 30 y. By establishing what are likely to be important mechanisms driving epochal trends in population immunity, we also identified key directions for future studies. In particular, our results highlight the need for longitudinal samples that are tested against multiple historical strains. This could lead to a better understanding of how, over the course of a lifetime, fast, transient antibody

  16. [Severe respiratory disease in an intensive care unit during influenza A(H1N1) 2009 pandemia].

    PubMed

    Aquino-Esperanza, José; Rodríguez, Pablo O; Boughen, Santiago; Raimondi, Alejandro; Attie, Shiry; Maskin, Patricio; Bonelli, Ignacio; Valentini, Ricardo

    2010-01-01

    We describe characteristics of patients admitted to our intensive care unit with severe acute respiratory illness and influenza-like syndrome during the first months of the pandemic influenza A(H1N1) 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66). A 54% (17) had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections) was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively). Six patients died (19%); they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset) was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043). There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities. PMID:20920955

  17. 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. PMID:20979988

  18. Clinical epidemiology and predictors of outcome in children hospitalised with influenza A(H1N1)pdm09 in 2009: a prospective national study

    PubMed Central

    Khandaker, Gulam; Zurynski, Yvonne; Ridley, Greta; Buttery, Jim; Marshall, Helen; Richmond, Peter C; Royle, Jenny; Gold, Michael; Walls, Tony; Whitehead, Bruce; McIntyre, Peter; Wood, Nicholas; Booy, Robert; Elliott, Elizabeth J

    2014-01-01

    Background There are few large-scale, prospective studies of influenza A(H1N1)pdm09 in children that identify predictors of adverse outcomes. Objectives We aimed to examine clinical epidemiology and predictors for adverse outcomes in children hospitalised with influenza A(H1N1)pdm09 in Australia. Methods Active hospital surveillance in six tertiary paediatric referral centres (June–September, 2009). All children aged <15 years admitted with laboratory-confirmed influenza A(H1N1)pdm09 were studied. Results Of 601 children admitted with laboratory-confirmed influenza, 506 (84·2%) had influenza A(H1N1)pdm09. Half (51·0%) of children with influenza A(H1N1)pdm09 were previously healthy. Hospital stay was longer in children with pre-existing condition (mean 6·9 versus 4·9 days; P = 0·02) as was paediatric intensive care unit (PICU) stay (7·0 versus 2·3 days; P = 0·005). Rapid diagnosis decreased both antibiotic use and length of hospital and PICU stay. Fifty (9·9%) children were admitted to a PICU, 30 (5·9%) required mechanical ventilation and 5 (0·9%) died. Laboratory-proven bacterial co-infection and chronic lung disease were significant independent predictors of PICU admission (OR 6·89, 95% CI 3·15–15·06 and OR 3·58, 95% CI 1·41–9·07, respectively) and requirement for ventilation (OR 5·61, 95% CI 2·2–14·28 and OR 5·18, 95% CI 1·8–14·86, respectively). Chronic neurological disease was a predictor of admission to PICU (OR 2·30, 95% CI 1·14–4·61). Conclusions During the 2009 pandemic, influenza was a major cause of hospitalisation in tertiary paediatric hospitals. Co-infection and underlying chronic disease increased risk of PICU admission and/or ventilation. Half the children admitted were previously healthy, supporting a role for universal influenza vaccination in children. PMID:25263176

  19. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.

    PubMed

    Jürchott, Karsten; Schulz, Axel Ronald; Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas; Babel, Nina; Thiel, Andreas; Neumann, Avidan Uriel

    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

  20. 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

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

    SciTech Connect

    Jaguin, Marie; Fardel, Olivier; Lecureur, Valérie

    2015-06-15

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

  2. Occurrence of AH1N1 viral infection and clinical features in symptomatic patients who received medical care during the 2009 influenza pandemic in Central Mexico

    PubMed Central

    2012-01-01

    Background In 2009 a new influenza serotype (AH1N1) was identified in Mexico that spread rapidly generating worldwide alarm. San Luis Potosi (SLP) was the third state with more cases reported in that year. The clinical identification of this flu posed a challenge to medical staff. This study aimed at estimating the AH1N1 infection, hospitalization and mortality rates, and at identifying related clinical features in persons who received medical care during the influenza pandemic. Methods Retrospective study with persons with flu-like illness who received public or private medical care in SLP from 15.03.09 to 30.10.09. Physicians purposely recorded many clinical variables. Samples from pharyngeal exudate or bronchoalveolar lavage were taken to diagnose AH1N1 using real-time PCR. Clinical predictors were identified using multivariate logistic regression with infection as a dependent variable. Odds ratios (OR) with 95% confidence intervals (CI) were computed. Analyses were stratified by age group based on the distribution of positive cases. Results From the 6922 persons with flu symptoms 6158 had available laboratory results from which 44.9% turned out to be positive for AH1N1. From those, 5.8% were hospitalized and 0.7% died. Most positive cases were aged 5–14 years and, in this subgroup, older age was positively associated with A H1N1 infection (95% CI 1.05-1.1); conversely, in patients aged 15 years or more, older age was negatively associated with the infection (95% CI 0.97-0.98). Fever was related in those aged 15 years or more (95% CI 1.4-3.5), and headache (95% CI 1.2-2.2) only in the 0–14 years group. Clear rhinorrhea and cough were positively related in both groups (p < 0.05). Arthralgia, dyspnea and vaccination history were related to lesser risk in persons aged 15 years or more, just as dyspnea, purulent rhinorrhea and leukocytosis were in the 0–14 years group. Conclusion This study identified various signs and symptoms for the clinical diagnosis

  3. Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

    PubMed Central

    Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

    2015-01-01

    Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

  4. Low Acceptability of A/H1N1 Pandemic Vaccination in French Adult Population: Did Public Health Policy Fuel Public Dissonance?

    PubMed Central

    Schwarzinger, Michaël; Flicoteaux, Rémi; Cortarenoda, Sébastien; Obadia, Yolande; Moatti, Jean-Paul

    2010-01-01

    Background In July 2009, French public health authorities embarked in a mass vaccination campaign against A/H1N1 2009 pandemic-influenza. We explored the attitudes and behaviors of the general population toward pandemic vaccination. Methodology/Principal Findings We conducted a cross-sectional online survey among 2,253 French representative adults aged 18 to 64 from November 17 to 25, 2009 (completion rate: 93.8%). The main outcome was the acceptability of A/H1N1 vaccination as defined by previous receipt or intention to get vaccinated (“Yes, certainly”, “Yes, probably”). Overall 17.0% (CI 95%, 15.5% to 18.7%) of respondents accepted A/H1N1 vaccination. Independent factors associated with acceptability included: male sex (p = .0001); older age (p = .002); highest or lowest level of education (p = .016); non-clerical occupation (p = .011); having only one child (p = .008); and having received seasonal flu vaccination in prior 3 years (p<.0001). Acceptability was also significantly higher among pregnant women (37.9%) and other at risk groups with chronic diseases (34.8%) (p = .002). Only 35.5% of respondents perceived A/H1N1 influenza illness as a severe disease and 12.7% had experienced A/H1N1 cases in their close relationships with higher acceptability (p<.0001 and p = .006, respectively). In comparison to 26.0% respondents who did not consult their primary care physician, acceptability was significantly higher among 8.0% respondents who were formally advised to get vaccinated, and lower among 63.7% respondents who were not advised to get vaccinated (respectively: 15.8%, 59.5% and 11.7%- p<.0001). Among respondents who refused vaccination, 71.2% expressed concerns about vaccine safety. Conclusions/Significance Our survey occurred one week before the peak of the pandemic in France. We found that alarming public health messages aiming at increasing the perception of risk severity were counteracted by daily personal experience which

  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 Central

    Houser, Katherine V.; Pearce, Melissa B.; Katz, Jacqueline M.

    2013-01-01

    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. PMID:24089569

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

    PubMed Central

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

    2016-01-01

    Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission. PMID:26733380

  7. Comparison of 2010-2011 H3N2 influenza A viruses isolated from swine and the A(H3N2)v isolated from humans in 2011

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the end of 2011, 12 U.S. cases of humans infected with swine H3N2 virus containing the matrix gene from pandemic H1N1 2009 virus (H1N1pdm09) were detected and named A(H3N2)v. This study used a swine model to compare the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2...

  8. Ah, Retirement! Hmm, Retirement?

    ERIC Educational Resources Information Center

    Vance, Jack O.

    1976-01-01

    Discusses the disadvantages of compulsory retirement at age 65 for senior business executives and suggests several possible ways companies can make good use of the experience and expertise of retirement-age executives. (Available from Business Horizons, School of Business, Indiana University, Bloomington, Indiana 47401; $2.50, single copy) (JG)

  9. Development of a selective modulator of aryl hydrocarbon (Ah) receptor activity that exhibits anti-inflammatory properties.

    PubMed

    Murray, Iain A; Krishnegowda, Gowdahalli; DiNatale, Brett C; Flaveny, Colin; Chiaro, Chris; Lin, Jyh-Ming; Sharma, Arun K; Amin, Shantu; Perdew, Gary H

    2010-05-17

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR in normal physiology is still an area of intense investigation. For example, this receptor plays an important role in certain immune responses. We have previously determined that the AHR can mediate repression of acute-phase genes in the liver. For this observation to be therapeutically useful, selective activation of the AHR would likely be necessary. Recently, the selective estrogen receptor ligand WAY-169916 has also been shown to be a selective AHR ligand. WAY-169916 can efficiently repress cytokine-mediated acute-phase gene expression (e.g., SAA1) yet fail to mediate a dioxin response element-driven increase in transcriptional activity. The goals of this study were to structurally modify WAY-169916 to block binding to the estrogen receptor and increase its affinity for the AHR. A number of WAY-169916 derivatives were synthesized and subjected to characterization as AHR ligands. The substitution of a key hydroxy group for a methoxy group ablates binding to the estrogen receptor and increases its affinity for the AHR. The compound 1-allyl-7-trifluoromethyl-1H-indazol-3-yl]-4-methoxyphenol (SGA 360), in particular, exhibited essentially no AHR agonist activity yet was able to repress cytokine-mediated SAA1 gene expression in Huh7 cells. SGA 360 was tested in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated ear inflammatory edema model using C57BL6/J and Ahr(-/-) mice. Our findings indicate that SGA 360 significantly inhibits TPA-mediated ear swelling and induction of a number of inflammatory genes (e.g., Saa3, Cox2, and Il6) in C57BL6/J mice. In contrast, SGA 360 had no effect on TPA-mediated ear swelling or inflammatory gene expression in Ahr(-/-) mice. Collectively, these results indicate that SGA 360 is a selective Ah receptor modulator (SAhRM) that exhibits anti

  10. Serum activin A and B, and follistatin in critically ill patients with influenza A(H1N1) infection

    PubMed Central

    2014-01-01

    Background Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients. Methods A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7. Results Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all). Conclusions Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure. PMID:24885241

  11. ITE and TCDD differentially regulate the vascular remodeling of rat placenta via the activation of AhR.

    PubMed

    Wu, Yanming; Chen, Xiao; Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

    2014-01-01

    Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

  12. ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR

    PubMed Central

    Zhou, Qian; He, Qizhi; Kang, Jiuhong; Zheng, Jing; Wang, Kai; Duan, Tao

    2014-01-01

    Vascular remodeling in the placenta is essential for normal fetal development. The previous studies have demonstrated that in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an environmental toxicant) induces the intrauterine fetal death in many species via the activation of aryl hydrocarbon receptor (AhR). In the current study, we compared the effects of 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and TCDD on the vascular remodeling of rat placentas. Pregnant rats on gestational day (GD) 15 were randomly assigned into 5 groups, and were exposed to a single dose of 1.6 and 8.0 mg/kg body weight (bw) ITE, 1.6 and 8.0 µg/kg bw TCDD, or an equivalent volume of the vehicle, respectively. The dams were sacrificed on GD20 and the placental tissues were gathered. The intrauterine fetal death was observed only in 8.0 µg/kg bw TCDD-exposed group and no significant difference was seen in either the placental weight or the fetal weight among all these groups. The immunohistochemical and histological analyses revealed that as compared with the vehicle-control, TCDD, but not ITE, suppressed the placental vascular remodeling, including reduced the ratio of the placental labyrinth zone to the basal zone thickness (at least 0.71 fold of control), inhibited the maternal sinusoids dilation and thickened the trophoblastic septa. However, no marked difference was observed in the density of fetal capillaries in the labyrinth zone among these groups, although significant differences were detected in the expression of angiogenic growth factors between ITE and TCDD-exposed groups, especially Angiopoietin-2 (Ang-2), Endoglin, Interferon-γ (IFN-γ) and placenta growth factor (PIGF). These results suggest ITE and TCDD differentially regulate the vascular remodeling of rat placentas, as well as the expression of angiogenic factors and their receptors, which in turn may alter the blood flow in the late gestation and partially resulted in

  13. Production impact of influenza A(H1N1)pdm09 virus infection on fattening pigs in Norway.

    PubMed

    Er, Chiek; Skjerve, Eystein; Brun, Edgar; Hofmo, Peer Ola; Framstad, Tore; Lium, Bjørn

    2016-02-01

    Newly emerged influenza A(H1N1)pdm09 virus infection in Norwegian pigs, although often observed in a subclinical form, can lower the pig's growth performance by reducing feed efficiency in terms of a poorer feed conversion ratio. Infected pigs would consume more feed and require protracted production time to reach market weight. In our observational longitudinal study, growth performance data from 728 control pigs and 193 infected pigs with known viral shedding time points were analyzed using mixed linear regression models to give estimates of the marginal effects of infection. Gaussian curves describing the variability of the estimates at the individual pig level formed the fundamental inputs to our stochastic models. The models were constructed to simulate the summed negative effects of the infection at the batch level of 150 fattening pigs growing from 33 to 100 kg. Other inputs of variability and uncertainty were 1) batch transmission points, 2) pig infection points to reflect the disease transmission dynamics of the virus, and 3) final prevalence of infected pigs in the batch. Monte Carlo random sampling gave 5,000 estimates on the outputs of the marginal effects for each pig. These results were summed up to provide estimates for a batch size of 150 pigs. This figure was adjusted by our final prevalence distribution function, which was also derived from the longitudinal study with 12 cohorts of infected pigs. For a 150-fattening-pig herd randomly selected from the population, the marginal effects of the infection were 1) 835 kg (fifth percentile) to 1,350 kg (95th percentile) increased feed intake and 2) 194 (fifth percentile) to 334 (95th percentile) pig days in excess of expected figures for an uninfected batch. A batch infected during growth phase 3 (81 to 100 kg BW) gave the worst results since the longitudinal study showed that a pig infected during growth phase 3 required more feed and a greater protracted production time compared to younger infected

  14. Clinical effectiveness of neuraminidase inhibitors--oseltamivir, zanamivir, laninamivir, and peramivir--for treatment of influenza A(H3N2) and A(H1N1)pdm09 infection: an observational study in the 2010-2011 influenza season in Japan.

    PubMed

    Shobugawa, Yugo; Saito, Reiko; Sato, Isamu; Kawashima, Takashi; Dapat, Clyde; Dapat, Isolde Caperig; Kondo, Hiroki; Suzuki, Yasushi; Saito, Kousuke; Suzuki, Hiroshi

    2012-12-01

    The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. In this study, we analyzed the clinical data of 211 patients infected with influenza A virus subtype H3N2 (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 influenza season. The duration of fever from the first dose of the NAI to fever alleviation to <37.5 °C was evaluated as an indicator of the clinical effectiveness of the NAIs in the influenza-infected patients. For the A(H3N2)-infected patients, Kaplan-Meier analysis showed the peramivir treatment group had the fastest time of fever alleviation to <37.5 °C (median 17.0 h, 95 % confidence interval [CI] 7.2-26.8 h) of the four treatment groups. No significant difference was found in the time to fever alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir. Results of multivariate analysis, using a Cox proportional-hazards model (hazard ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status, time from onset to the clinic visit, and body temperature showed significantly faster fever alleviation in the peramivir treatment group compared with the oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the oseltamivir and zanamivir treatment groups were compared, and no significant difference in time to alleviation of fever was observed between the two groups. Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring oseltamivir resistance. Further evaluation of the clinical effectiveness of the newly released NAIs for influenza-infected patients, including those infected with A(H1N1)pdm09, is needed. PMID:22644080

  15. Use of Cumulative Incidence of Novel Influenza A/H1N1 in Foreign Travelers to Estimate Lower Bounds on Cumulative Incidence in Mexico