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Sample records for glufosinate antagonizes clethodim

  1. Bermudagrass (Cynodon spp) dose-response relationships with clethodim, glufosinate and glyphosate.

    Science.gov (United States)

    Webster, Theodore M; Hanna, Wayne W; Mullinix, Benjamin G

    2004-12-01

    Greenhouse studies were conducted to evaluate the sensitivity of three commercial cultivars, eight experimental cultivars and common bermudagrass to clethodim, glufosinate and glyphosate. Each herbicide was applied at eight doses. Data were regressed on herbicide dose using a log-logistic curve (R2 = 0.56-0.95 for clethodim, R2 = 0.60-0.94 for glufosinate, and R2 = 0.70-0.96 for glyphosate). The herbicide rate that elicited a 50% plant response (I50) in the bermudagrass cultivars ranged from 0.04 to 0.19 kg ha(-1) clethodim, 0.19 to 1.33 kg ha(-1) glufosinate and 0.34 to 1.14 kg ha(-1) glyphosate. Relative to other cultivars, common bermudagrass was intermediate in its response to clethodim and among the most tolerant cultivars to glufosinate and glyphosate. TifSport was relatively tolerant to clethodim and glufosinate compared with other cultivars, but relatively sensitive to glyphosate. One cultivar, 94-437, was consistently among the most sensitive cultivars to each of the herbicides. While there were differential herbicide tolerances among the tested bermudagrass cultivars, there did not appear to be any naturally occurring herbicide resistance that could be commercially utilized. However, research indicated that breeding efforts should target herbicide resistance that is at least four times the registered use rate. Also, TifSport and Tifway have been identified as suitable representatives of triploid hybrid bermudagrass cultivars to be used to evaluate the success of turfgrass renovation programs. 2004 Society of Chemical Industry.

  2. 75 FR 26673 - Clethodim; Pesticide Tolerances

    Science.gov (United States)

    2010-05-12

    ... regulation establishes tolerances for residues of clethodim in or on the raw agricultural commodity artichoke... clethodim, in or on the raw agricultural commodity artichoke, globe at 1.3 parts per million (ppm... bushberry subgroup 13-07B tolerance from 3.0 ppm to 0.20 ppm and the globe artichoke tolerance from 1.3 ppm...

  3. Assessment of Poa annua resistance to clethodim in Costa Rica

    International Nuclear Information System (INIS)

    Rodriguez-Ruiz, Ana Maria; Herrera-Murillo, Franklin; Chaves-Barrantes, Nestor; Hernandez-Diaz, Alberto

    2015-01-01

    The presence of resistance to clethodim in Poa annua populations was observed in onion fields in the highlands of Cartago, Costa Rica. Two experiments were conducted; the first one was carried out, in 2007, in a greenhouse at the Fabio Baudrit Moreno Agricultural Experiment Station (EEAFBM, in Spanish), with seeds of plants from a farm where clethodim has exercised good control (S population), and from another farm where clethodim has showed a deficient control (R population). Both S and R populations were treated with different doses of clethodim (0,5X, 1,0X, 1,5X and 2,0X), being X the recommended commercial dose. In this experiment, control of the R population was 44% and 17% at doses of 1.5X and 2.0X, respectively, whereas control of the S population was 100% at either of those doses. The second experiment was carried out in 2009, seeds of two other P. annua populations were collected in a similar way: one population from an area where weed control has been satisfactory (S), and the other population from an area of the farm where control was deficient (R). Seeds were sown, depending on the type, in plastic pots and sprayed with clethodim at doses of: 0. 1X, 2X, 4X, 8X, and 16X. There were significant differences in the reactions to clethodim of both P. annua populations The S population showed a higher percentage of control and less surviving plants than the R population. Several plants of the R population resisted up to 16X commercial doses of clethodim. Results of both experiments suggest the presence of P. annua populations resistant to clethodim. (author) [es

  4. Assessment of Poa annua resistance to clethodim in Costa Rica.

    Directory of Open Access Journals (Sweden)

    Ana María Rodríguez-Ruiz

    2015-06-01

    Full Text Available The objective of this study was to check for the presence of resistance to clethodim in Poa annua populations observed in onion fields in the highlands of Cartago, Costa Rica. Two experiments were conducted; the first one was carried out, in 2007, in a greenhouse at the Fabio Baudrit Moreno Agricultural Experiment Station (EEAFBM, in Spanish, with seeds of plants from a farm where clethodim exercised good control (S population, and from another farm where clethodim showed a deficient control (R population. Both S and R populations were treated with different doses of clethodim (0.5X, 1.0X, 1.5X and 2.0X, being X the recommended commercial dose. In this experiment, control of the R population was 44% and 17% at doses of 1.5X and 2.0X, respectively, whereas control of the S population was 100% at either of those doses. The second experiment was carried out in 2009, seeds of two other P. annua populations were collected in a similar way: one population from an area where weed control was satisfactory (S, and the other population from an area of the farm where control was deficient (R. Seeds were sown, depending on the type, in plastic pots and sprayed with clethodim at doses of: 0. 1X, 2X, 4X, 8X, and 16X. There were significant differences in the reactions to clethodim of both P. annua populations The S population showed a higher percentage of control and less surviving plants than the R population. Several plants of the R population resisted up to 16X commercial doses of clethodim. Results of both experiments suggest the presence of P. annua populations resistant to clethodim.

  5. Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum.

    Science.gov (United States)

    Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T

    2000-09-01

    Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

  6. Glufosinate ammonium selection of transformed Arabidopsis.

    Science.gov (United States)

    Weigel, Detlef; Glazebrook, Jane

    2006-12-01

    INTRODUCTIONOne of the most commonly used markers for the selection of transgenic Arabidopsis is resistance to glufosinate ammonium, an herbicide that is sold under a variety of trade names including Basta and Finale. Resistance to glufosinate ammonium is conferred by the bacterial bialophos resistance gene (BAR) encoding the enzyme phosphinotricin acetyl transferase (PAT). This protocol describes the use of glufosinate ammonium to select transformed Arabidopsis plants. The major advantage of glufosinate ammonium selection is that it can be performed on plants growing in soil and does not require the use of sterile techniques.

  7. Inheritance of evolved clethodim resistance in Lolium rigidum populations from Australia.

    Science.gov (United States)

    Saini, Rupinder Kaur; Malone, Jenna; Gill, Gurjeet; Preston, Christopher

    2017-08-01

    In Australia, the extensive use of clethodim for the control of Lolium rigidum has resulted in the evolution of many clethodim-resistant L. rigidum populations. Five clethodim-resistant populations of L. rigidum were analysed for the inheritance of clethodim resistance. Reciprocal crosses were made between resistant (R) and susceptible (S) populations. Within crosses, dose-responses of reciprocal F 1 families of all populations except A61 were similar to each other, indicating that clethodim resistance in these populations is encoded on the nuclear genome. The level of dominance observed in the dose-response experiments ranged from partial to complete within the herbicide rate used. In the A61 population, within each cross, the response of F 1 from the maternal and paternal parent was different, indicating that resistance is inherited through the female parent. All backcross populations segregated in a different manner. Only one population, FP, fitted a single-gene model (1:1). Two populations fitted two-gene models: a 3:1 inheritance model for F4 and a 1:3 inheritance model for A91. For population E2, no clear pattern of inheritance was determined, suggesting more complex inheritance. The results of this study indicate that different patterns of clethodim resistance in L. rigidum exist. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Chronotoxicity of glufosinate ammonium in mice.

    Science.gov (United States)

    Yoshiyama, Y; Kobayashi, T; Kondo, R; Tomonaga, F; Ohwada, T

    1995-02-01

    The effect of a circadian-stage dependent dosing schedule on the toxicity of glufosinate was studied in mice. Male ICR mice were housed in a standardized 12:12 light:dark cycle for 3 w. Each animal was given 1500 or 3000 mg glufosinate/kg po. A highly significant circadian rhythm occurred in the resulting mortality, with the highest mortality from doses given during the light phase and the lowest from doses administered during the dark phase. The circadian-stage dependent dosing schedule had a marked influence on the pattern of acute glufosinate toxicity in mice.

  9. 40 CFR 180.473 - Glufosinate ammonium; tolerances for residues.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Glufosinate ammonium; tolerances for... § 180.473 Glufosinate ammonium; tolerances for residues. (a) General. Tolerances are established for residues of the herbicide glufosinate-ammonium (butanoic acid, 2-amino-4-(hydroxymethylphosphinyl...

  10. Characterisation of glufosinate resistance mechanisms in Eleusine indica.

    Science.gov (United States)

    Jalaludin, Adam; Yu, Qin; Zoellner, Peter; Beffa, Roland; Powles, Stephen B

    2017-06-01

    An Eleusine indica population has evolved resistance to glufosinate, a major post-emergence herbicide of global agriculture. This population was analysed for target-site (glutamine synthetase) and non-target-site (glufosinate uptake, translocation and metabolism) resistance mechanisms. Glutamine synthetase (GS) activity extracted from susceptible (S) and resistant (R*) plants was equally sensitive to glufosinate inhibition, with IC 50 values of 0.85 mm and 0.99 mm, respectively. The extractable GS activity was also similar in S and R* samples. Foliar uptake of [ 14 C]-glufosinate did not differ in S and R* plants, nor did glufosinate net uptake in leaf discs. Translocation of [ 14 C]-glufosinate into untreated shoots and roots was also similar in both populations, with 44% to 47% of the herbicide translocated out from the treated leaf 24 h after treatment. The HPLC and LC-MS analysis of glufosinate metabolism revealed no major metabolites in S or R* leaf tissue. Glufosinate resistance in this resistant population is not due to an insensitive GS, or increased activity, or altered glufosinate uptake and translocation, or enhanced glufosinate metabolism. Thus, target-site resistance is likely excluded and the exact resistance mechanism(s) remain to be determined. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  11. Neurological effects of glufosinate poisoning with a brief review.

    Science.gov (United States)

    Watanabe, T; Sano, T

    1998-01-01

    Herbicides containing glufosinate ammonium are widely used in many countries including Japan. Many Japanese cases of accidental and suicidal poisoning by glufosinate have been reported since 1989. We report a case of a 64-year old man who ingested glufosinate in an attempted suicide. The patient suffered mental disturbances and hematological changes together with gastrointestinal effects shortly after ingesting the poison, and later developed generalized convulsions, impaired respiration and circulatory failure. During recovery he exhibited loss of short-term memory (retrograde and anterograde amnesia). Neurotoxicity is a characteristic of glufosinate poisoning, although the mechanism is not clear. From the analysis of clinical symptoms of previously published cases, glufosinate toxicity appears to arise both from the active ingredient and the surfactant in the formulation.

  12. Rapeseed with tolerance to the non selective herbicide glufosinate ammonium

    Energy Technology Data Exchange (ETDEWEB)

    Rasche, E. [Hoechst Schering AgrEvo GmbH, Frankfurt am Main (Germany)

    1998-12-31

    Weed control with herbicides is essential to grow rapeseed. Glufosinate Ammonium is used as a non selective herbicide successfully in many countries for over 10 years. It conforms well with ever increasing safety standards for human beings, animals and the environment. The tolerance of rapeseed and other crop plants was achieved by genetic modification. A resistance gene (PAT or BAR) was transfered into previously susceptible rapeseed plants. This new approach allowed the development of Glufosinate Ammonium as an almost ideal selective herbicide. In cooperation with major seed companies and by own breeding programmes new Glufosinate tolerant rapeseed varieties and hybrids are developed. Data on metabolism, toxicity, residues, efficacy etc. were generated to get registration for the selective herbicide use. In addition various studies were done for safety assessments of the PAT gene and the modified rapeseed. In spring 1995 Canadian authorities granted worldwide the first approvals for the selective use of Glufosinate Ammonium (trademark Liberty) and Glufosinate tolerant (trademark and logo Liberty Link) spring rapeseed (Canola). After a successful launch in 1995 about 150.000 ha of Liberty Link Canola were grown and treated with Liberty in 1996. The Liberty Link Canola growers were very well satisfied. In a grower survey 84% stated that they will definitely use the Liberty Link System again. In Europe registrations for Glufosinate Ammonium as a selective herbicide and for the first Glufosinate tolerant rapeseed varieties are expected in the course of 1997. The Liberty Link System will be launched in rapeseed most probably in 1998. (orig.)

  13. A toxicokinetic analysis in a patient with acute glufosinate poisoning.

    Science.gov (United States)

    Hirose, Y; Kobayashi, M; Koyama, K; Kohda, Y; Tanaka, T; Honda, H; Hori, Y; Yoshida, K; Kikuchi, M

    1999-05-01

    Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2alpha of 1.84 and T1/2beta of 9.59 h. The apparent distribution volume at beta-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/min. The indication for extracorporeal hemopurification for this poisoning has been discussed.

  14. Glufosinate Herbicide Intoxication Causing Unconsciousness, Convulsion, and 6th Cranial Nerve Palsy

    OpenAIRE

    Park, Jae-seok; Kwak, Soo-Jung; Gil, Hyo-wook; Kim, So-Young; Hong, Sae-yong

    2013-01-01

    Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on six...

  15. Apoptosis induced by glufosinate ammonium in the neuroepithelium of developing mouse embryos in culture.

    Science.gov (United States)

    Watanabe, T

    1997-01-24

    Glufosinate ammonium structurally resembles glutamate and blocks glutamine synthetase. Glufosinate was recently found to be dysmorphogenic in mammals in vitro. The present study examined the cell death induced specifically by glufosinate in the neuroepithelium of mouse embryos. Electron micrograph revealed characteristic chromatin condensation and segregation, extracellular apoptotic bodies, and cell fragments phagocytosed in macrophages in the neuroepithelium of the brain vesicle and neural tube. Moreover neuroepithelial cells undergoing DNA fragmentation were histochemically identified. DNA gel electrophoresis of the neuroepithelial layer revealed a DNA ladder. These observations demonstrate that glufosinate specifically induced apoptosis in the neuroepithelium of embryos.

  16. SENSITIVITY OF MORNINGGLORY PLANTS AND THEIR PROGENIES TO GLUFOSINATE AMMONIUM

    OpenAIRE

    BRITO, I.P.F.S.; MORAES, C.P.; MARCHESI, B.B.; CARBONARI, C.A.; VELINI, E.D.

    2017-01-01

    ABSTRACT The sensitivity of weed species to herbicides is variable, and the behavior can be repeated or not in the next generation. The objective of this study was to evaluate the response of morningglory plants to different doses of glufosinate ammonium and the sensitivity of plant populations and their progenies to the herbicide. Three studies were conducted, all in a greenhouse and repeated in two periods. In the first study, two experiments were conducted to examine the dose-response curv...

  17. Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

    Science.gov (United States)

    Matsumura, N; Takeuchi, C; Hishikawa, K; Fujii, T; Nakaki, T

    2001-05-18

    Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

  18. First Case of Glufosinate-Resistant Rigid Ryegrass (Lolium rigidum Gaud. in Greece

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    Ilias S. Travlos

    2018-03-01

    Full Text Available Repeated applications of the same herbicide(s, which are characterized by the same mode of action, increase selection pressure, which in turn favours the evolution of herbicide-resistant weeds. Glufosinate is a broad-spectrum non-selective herbicide being used for weed control for many years around the world. Rigid ryegrass (Lolium rigidum Gaud. is an economically important grass weed in Greece. Recent complaints by growers about control failure of rigid ryegrass with glufosinate require further investigation and have been the basis of this study. The objectives of this study were to confirm the existence of glufosinate-resistant L. rigidum in Greece and evaluate the effect of L. rigidum growth stage on glufosinate efficacy. Twenty populations of rigid ryegrass from Greece were sampled from five regions, and whole plant dose–response studies were conducted for five populations under controlled conditions with eight rates of glufosinate (0.0, 0.098, 0.187, 0.375, 0.75, 1.5, 3.0, and 6.0 kg a.i. ha−1. Glufosinate resistance was confirmed in three out of five populations with the level of resistance ranging from three-to seven-fold compared with the susceptible populations based on above-ground biomass reduction. Results also revealed that the level of glufosinate-resistance of rigid ryegrass was dependent on the growth stage at which it was applied.

  19. Field dissipation and storage stability of glufosinate ammonium and its metabolites in soil.

    Science.gov (United States)

    Zhang, Yun; Wang, Kai; Wu, Junxue; Zhang, Hongyan

    2014-01-01

    A simple analytical method was developed to measure concentrations of glufosinate ammonium and its metabolites, 3-methylphosphinico-propionic acid (MPP) and 2-methylphosphinico-acetic acid (MPA), in field soil samples. To determine the minimum quantification limit, samples were spiked at different levels (0.1, 0.5, and 1.0 mg/kg). Soil samples were extracted with ammonium hydroxide solution 5% (v/v), concentrated, and reacted with trimethyl orthoacetate (TMOA) in the presence of acetic acid for derivatization. The derivatives were quantified by gas chromatography (GC) using a flame photometric detector (FPD). The linear correlation coefficients of glufosinate ammonium, MPP, and MPA in soil were 0.991, 0.999, and 0.999, respectively. The recoveries of this method for glufosinate ammonium, MPP, and MPA in soil were 77.2-95.5%, 98.3-100.3%, and 99.3-99.6% with relative standard deviations (RSD) of 1.8-4.1%, 0.4-1.4%, and 1.3-2.0%, respectively. Glufosinate ammonium dissipated rapidly in soil to MPA in hours and gradually degraded to MPP. The half-life of glufosinate ammonium degradation in soil was 2.30-2.93 days in an open field. In soil samples stored at -20°C glufosinate ammonium was stable for two months. The results of this study should provide guidance for the safe application of the herbicide glufosinate ammonium to agricultural products and the environment.

  20. Photoelectrochemical detection of the herbicide clethodim by using the modified metal-organic framework amino-MIL-125(Ti)/TiO2

    International Nuclear Information System (INIS)

    Jin, Dangqin; Yu, Liangyun; Xu, Qin; Hu, Xiaoya

    2015-01-01

    We describe a sensitive photoelectrochemical (PEC) sensor for the determination of the herbicide clethodim. The PEC sensor was constructed by using amino-MIL-125/TiO 2 (MIL stands for Materials from Institute Lavoisier), an amino-functionalized metal-organic framework (MOF) modified with TiO2. The amino-MIL-125/TiO 2 was synthesized by a simple one-step solvothermal method and placed on a glassy carbon electrode where it displays photoelectrocatalytic activity. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy and X-ray diffractometry (XRD) were used to characterize the amino-MIL-125/TiO2. In the sensing process, amino-MIL-125/TiO 2 is illuminated by visible light to produce electrons. These excited electrons are delivered to the glassy carbon electrode, leaving positively charged holes (h+) on the surface of the amino-MIL-125/TiO 2 . The holes react with H 2 O to generate hydroxy radicals (•OH). Clethodim rapidly attacks the hydroxy radicals and improves the efficiency of charge separation, this leading to an enhanced photocurrent. Under the optimal experimental conditions, this photoelectrochemical method enables clethodim to be quantified in the concentration range from 0.2 to 25 μmol L −1 , with a detection limit (3 S/N) of 10 nmol L −1 . The assay was applied to the determination of clethodim in soil samples, and results were in acceptable agreement with data obtained by liquid chromatography/mass spectrometry. (author)

  1. Circadian response of annual weeds to glyphosate and glufosinate.

    Science.gov (United States)

    Martinson, Krishona B; Sothern, Robert B; Koukkari, Willard L; Durgan, Beverly R; Gunsolus, Jeffrey L

    2002-03-01

    Five field experiments were conducted in 1998 and 1999 in Minnesota to examine the influence of time of day efficacy of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [2-amino-4-(hydroxymethyl-phosphinyl)butanoic acid] applications on the control of annual weeds. Each experiment was designed to be a randomized complete block with four replications using plot sizes of 3 x 9 m. Glyphosate and glufosinate were applied at rates of 0.421 kg ae/ha and 0.292 kg ai/ha, respectively, with and without an additional adjuvant that consisted of 20% nonionic surfactant and 80% ammonium sulfate. All treatments were applied with water at 94 L/ha. Times of day for the application of herbicide were 06:00h, 09:00h, 12:00h, 15:00h, 18:00h, 21:00h, and 24:00h. Efficacy was evaluated 14 d after application by visual ratings. At 14 d, a circadian response to each herbicide was found, with greatest annual weed control observed with an application occurring between 09:00h and 18:00h and significantly less weed control observed with an application at 06:00h, 21:00h, or 24:00h. The addition of an adjuvant to both herbicides increased overall efficacy, but did not overcome the rhythmic time of day effect. Results of the multiple regression analysis showed that after environmental temperature, time of day was the second most important predictor of percent weed kill. Thus, circadian timing of herbicide application significantly influenced weed control with both glyphosate and glufosinate.

  2. Glufosinate (phosphinothricin), a natural amino acid with unexpected herbicidal properties.

    Science.gov (United States)

    Hoerlein, G

    1994-01-01

    Glufosinate ammonium (phosphinothricin ammonium) (GLA) is the active ingredient of Basta and several other herbicides used worldwide. It is produced as part of the tripeptide L-phosphinothricyl-L-alanyl-L-alanin, which was first isolated from Streptomyces viridichromogenes or Streptomyces hygroscopicus. Its structure is confirmed by degradation and synthesis. Several processes for the preparation of D,L- and L-phosphinothricin are described. Glufosinate is a structural analog of glutamate and inhibits the glutamine synthetase. The result is a rapid build-up of a high ammonia level and a concomitant depletion of glutamine and several other amino acids in the plant. These effects are accompanied by a rapid decline of photosynthetic CO2-fixation and are followed by chlorosis and desiccation. The results of numerous toxicological studies show that glufosinate ammonium and its commercial formulations are safe for users and consumers under the conditions of recommended use. The fast and complete degradation in soil and surface water prevents movement of residues into groundwater. The toxicological threshold levels for all the nontarget organisms tested are well above the potential exposure levels and therefore do not reflect any hazard for nontarget organisms in the ecosystem. Basta is a nonselective foliar applied herbicide for the control of undesirable mono- and dicotyledonous plants in orchards, vineyards, and plantations for minimum tillage, and as a harvest aid. A synthetic phosphinothricin acetyltransferase (PAT) gene has been introduced via Agrobacterium tumefaciens into dicot crops, such as like tobacco, tomato, spring and winter rapeseed, alfalfa, and several horticultural crops. The PAT gene was also successfully introduced into maize protoplasts that could be regenerated into fertile plants. All transgenic crop plants tolerated a two- to threefold field dosage of Basta.

  3. Glufosinate herbicide intoxication causing unconsciousness, convulsion, and 6th cranial nerve palsy.

    Science.gov (United States)

    Park, Jae-seok; Kwak, Soo-Jung; Gil, Hyo-wook; Kim, So-Young; Hong, Sae-yong

    2013-11-01

    Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.

  4. VARIATION IN THE SENSITIVITY OF WANDERING JEW PLANTS TO GLUFOSINATE AMMONIUM

    OpenAIRE

    BRITO, IVANA PAULA FERRAZ SANTOS DE; MARCHESI, BRUNA BARBOZA; SILVA, ILCA PUERTAS FREITAS E; CARBONARI, CAIO ANTONIO; VELINI, EDIVALDO DOMINGUES

    2017-01-01

    ABSTRACT This study aimed to identify the response of wandering jew (Commelina benghalensis L.) plants to different doses of glufosinate ammonium and the sensitivity of plants populations to the herbicide. Two studies were conducted, both in a greenhouse, and were repeated at different times. In the first study, two experiments were conducted to examine the dose-response curve using seven different doses of the glufosinate ammonium herbicide (0, 50, 100, 200, 400, 800, and 1600 g a.i. ha-1) w...

  5. Glyphosate and glufosinate-ammonium runoff from a corn-growing area in Italy

    OpenAIRE

    Screpanti , Claudio; Accinelli , Cesare; Vicari , Alberto; Catizone , Pietro

    2005-01-01

    International audience; The main objective of this experiment was to estimate field-scale runoff losses of glyphosate and glufosinate-ammonium under natural rainfall conditions. Investigations were carried out at the Runoff Monitoring Station of the University of Bologna (Italy). Glyphosate and glufosinate-ammonium were applied as pre-emergence herbicides on 350-m2 field plots characterized by a uniform slope of 15%. Field plots were cultivated with corn. The persistence and sorption isotherm...

  6. VARIATION IN THE SENSITIVITY OF WANDERING JEW PLANTS TO GLUFOSINATE AMMONIUM

    OpenAIRE

    IVANA PAULA FERRAZ SANTOS DE BRITO; BRUNA BARBOZA MARCHESI; ILCA PUERTAS FREITAS E SILVA; CAIO ANTONIO CARBONARI; EDIVALDO DOMINGUES VELINI

    2017-01-01

    This study aimed to identify the response of wandering jew (Commelina benghalensis L.) plants to different doses of glufosinate ammonium and the sensitivity of plants populations to the herbicide. Two studies were conducted, both in a greenhouse, and were repeated at different times. In the first study, two experiments were conducted to examine the dose-response curve using seven different doses of the glufosinate ammonium herbicide (0, 50, 100, 200, 400, 800, and 1600 g a.i. ha-1) with four ...

  7. Nitrogen loss in Brachiaria decumbens after application of glyphosate or glufosinate-ammonium

    OpenAIRE

    Damin,Virginia; Franco,Henrique Coutinho Junqueira; Moraes,Milton Ferreira; Franco,Ademir; Trivelin,Paulo Cesar Ocheuze

    2008-01-01

    Nitrogen losses from the soil-plant system may be influenced by herbicide applications. In order to evaluate N loss in brachiaria (Brachiaria decumbens) after application of the herbicides glyphosate and glufosinate-ammonium, an experiment was carried out in a greenhouse as a completely randomized design, with three treatments and six replicates. Treatments were as follows: i) desiccation of brachiaria-plants with glyphosate; ii) desiccation of brachiaria-plants with glufosinate-ammonium; and...

  8. A comparative study of direct hemoperfusion and hemodialysis for the removal of glufosinate ammonium.

    Science.gov (United States)

    Tanaka, J; Yamashita, M; Yamamoto, T

    1995-01-01

    BASTA is a herbicide containing glufosinate ammonium 18.5% and a surface-active agent. There were six fatalities in 34 cases of glufosinate ammonium poisoning reported by the Japan Poison Information Center. To evaluate efficacy in the removal of glufosinate ammonium from the blood, two bottles were prepared containing 600 mL of heparinized bovine blood with 1 mL or 3 mL of BASTA. Direct hemoperfusion or hemodialysis was performed for two hours at a flow rate of 50 mL/min. The final glufosinate ammonium concentration of the blood bottle containing 1 mL of BASTA decreased to 96.9% of the initial concentration after direct hemoperfusion and to 0.5% after hemodialysis. The final glufosinate ammonium concentration of the bottle containing 3 mL of BASTA decreased to 62.2% after direct hemoperfusion and to 0.9% after hemodialysis. Hemodialysis is more effective than direct hemoperfusion for removal of glufosinate ammonium from blood.

  9. Glufosinate ammonium--some aspects of its mode of action in mammals.

    Science.gov (United States)

    Hack, R; Ebert, E; Ehling, G; Leist, K H

    1994-05-01

    The broad-spectrum herbicide glufosinate ammonium is a structural analogue of glutamate and acts in plants by inhibition of glutamine synthetase leading to a complete breakdown of ammonia metabolism. Owing to the structural analogy of glufosinate ammonium to glutamate, its effect on various glutamate-utilizing systems needed to be investigated in mammals. Although in laboratory animals glufosinate ammonium causes an inhibition of glutamine synthetase activity in different tissues, this inhibition led to slight increases of glutamate and ammonia levels at high sublethal and lethal doses only. After oral administration for 28 days, glufosinate ammonium had no effect on glutathione and carbohydrate metabolism and no effect on biosynthesis of non-essential amino acids in rats and dogs. Glufosinate ammonium does not interfere with various neurotransmitter receptors in vitro and does not influence the catecholamine neurotransmitter tissue concentrations after iv application. The results of these studies show that--in contrast to the plant metabolism--in mammals the inhibition of glutamine synthetase activity in various tissues does not lead to a breakdown of ammonia metabolism. The mammalian metabolism obviously compensates for this inhibition of glutamine synthetase activity by various other metabolic pathways. It is concluded that under the conditions of recommended use of glufosinate ammonium as an active ingredient in herbicides, a detrimental effect on the health of both users and consumers is extremely unlikely.

  10. Glufosinate Ammonium-Induced Pathogen Inhibition and Defense Responses Culminate in Disease Protection in bar-Transgenic Rice1[C

    Science.gov (United States)

    Ahn, Il-Pyung

    2008-01-01

    Glufosinate ammonium diminished developments of rice (Oryza sativa) blast and brown leaf spot in 35S:bar-transgenic rice. Pre- and postinoculation treatments of this herbicide reduced disease development. Glufosinate ammonium specifically impeded appressorium formation of the pathogens Magnaporthe grisea and Cochliobolus miyabeanus on hydrophobic surface and on transgenic rice. In contrast, conidial germination remained unaffected. Glufosinate ammonium diminished mycelial growth of two pathogens; however, this inhibitory effect was attenuated in malnutrition conditions. Glufosinate ammonium caused slight chlorosis and diminished chlorophyll content; however, these alterations were almost completely restored in transgenic rice within 7 d. Glufosinate ammonium triggered transcriptions of PATHOGENESIS-RELATED (PR) genes and hydrogen peroxide accumulation in transgenic rice and PR1 transcription in Arabidopsis (Arabidopsis thaliana) wild-type ecotype Columbia harboring 35S:bar construct. All transgenic Arabidopsis showed robust hydrogen peroxide accumulation by glufosinate ammonium. This herbicide also induced PR1 transcription in etr1 and jar1 expressing bar; however, no expression was observed in NahG and npr1. Fungal infection did not alter transcriptions of PR genes and hydrogen peroxide accumulation induced by glufosinate ammonium. Infiltration of glufosinate ammonium did not affect appressorium formation of M. grisea in vivo but inhibited blast disease development. Hydrogen peroxide scavengers nullified blast protection and transcriptions of PR genes by glufosinate ammonium; however, they did not affect brown leaf spot progression. In sum, both direct inhibition of pathogen infection and activation of defense systems were responsible for disease protection in bar-transgenic rice. PMID:17981989

  11. Glufosinate ammonium-induced pathogen inhibition and defense responses culminate in disease protection in bar-transgenic rice.

    Science.gov (United States)

    Ahn, Il-Pyung

    2008-01-01

    Glufosinate ammonium diminished developments of rice (Oryza sativa) blast and brown leaf spot in 35S:bar-transgenic rice. Pre- and postinoculation treatments of this herbicide reduced disease development. Glufosinate ammonium specifically impeded appressorium formation of the pathogens Magnaporthe grisea and Cochliobolus miyabeanus on hydrophobic surface and on transgenic rice. In contrast, conidial germination remained unaffected. Glufosinate ammonium diminished mycelial growth of two pathogens; however, this inhibitory effect was attenuated in malnutrition conditions. Glufosinate ammonium caused slight chlorosis and diminished chlorophyll content; however, these alterations were almost completely restored in transgenic rice within 7 d. Glufosinate ammonium triggered transcriptions of PATHOGENESIS-RELATED (PR) genes and hydrogen peroxide accumulation in transgenic rice and PR1 transcription in Arabidopsis (Arabidopsis thaliana) wild-type ecotype Columbia harboring 35S:bar construct. All transgenic Arabidopsis showed robust hydrogen peroxide accumulation by glufosinate ammonium. This herbicide also induced PR1 transcription in etr1 and jar1 expressing bar; however, no expression was observed in NahG and npr1. Fungal infection did not alter transcriptions of PR genes and hydrogen peroxide accumulation induced by glufosinate ammonium. Infiltration of glufosinate ammonium did not affect appressorium formation of M. grisea in vivo but inhibited blast disease development. Hydrogen peroxide scavengers nullified blast protection and transcriptions of PR genes by glufosinate ammonium; however, they did not affect brown leaf spot progression. In sum, both direct inhibition of pathogen infection and activation of defense systems were responsible for disease protection in bar-transgenic rice.

  12. Transformation of the herbicide [14C]glufosinate in soils

    International Nuclear Information System (INIS)

    Smith, A.E.

    1989-01-01

    The degradation of 2 μg/g [ 14 C]glufosinate (DL-homoalan-4-ylmethylphosphinic acid) was studied in clay, clay loam, and sandy loam soils at 85% field capacity and at 20 degree C. Over a 4-week period the soils were extracted and analyzed for transformation products by radiochemical and gas chromatographic techniques. In all soils there was release of [ 14 C]carbon dioxide and formation of [ 14 C]-3-(hydroxymethylphosphinyl)propionic acid (MPPA) as major degradation products. Within 21 days, about 55% of the applied 14 C herbicide had been transformed to MPPA in the sandy loam and 19% to [ 14 C]carbon dioxide. After 28 days, approximately 45% of the 14 C herbicide had been transformed to MPPA in the clay and clay loam and 10% released as [ 14 C]carbon dioxide. At all samplings, other 14 C transformation products appeared to be insignificant

  13. Summary of safety evaluation toxicity studies of glufosinate ammonium.

    Science.gov (United States)

    Ebert, E; Leist, K H; Mayer, D

    1990-05-01

    This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

  14. Reversible Splenial Lesion Syndrome (RESLES) Following Glufosinate Ammonium Poisoning.

    Science.gov (United States)

    Jeong, Tae Oh; Yoon, Jae Chol; Lee, Jae Baek; Jin, Young Ho; Hwang, Seung Bae

    2015-01-01

    Isolated and reversible lesion restricted to the splenium of the corpus callosum, known as reversible splenial lesion syndrome, have been reported in patients with infection, high-altitude cerebral edema, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Here, we report a 39-year-old female patient with glufosinate ammonium (GLA) poisoning who presented with confusion and amnesia. Diffusion-weighted magnetic resonance imaging of the brain revealed cytotoxic edema of the splenium of the corpus callosum. The lesion was not present on follow-up MR imaging performed 9 months later. We postulate that a GLA-induced excitotoxic mechanism was the cause of this reversible splenial lesion. Copyright © 2015 by the American Society of Neuroimaging.

  15. Avaliação da eficiência de controle de plantas daninhas gramíneas do herbicida clethodim em algodoeiro herbáceo (Gossypium hirsutum var. latifolium Hutch. Evaluation of the efficiency on the control of gramineous weeds by the herbicide clethodim in a herbaceous cotton crop (Gossypium hirsutum var. latifolium Hutch.

    Directory of Open Access Journals (Sweden)

    J.P. Laca-Buendia

    1992-01-01

    Full Text Available Com o objetivo de conhecer a eficiência do herbicida clethodim no controle de plantas daninhas gramíneas e seu comportamento seletivo na cultura do algodão, cv. IAC-20, foi instalado um experimento em solo aluvial de textura arenosa. Foram estudados os seguintes tratamentos: clethodim + óleo mineral nas doses de 0,84 0,96 e 0,108 kg/ha + 0,5 % v/v, sethoxydim + óleo mineral a 0,23 kg/ha + 0,5% v/v em pós-emergência, alachlor a 2,4 kg/ha em pós-emergência, trifluralin a 0,89 kg/ha em pós-plantio incorporado, uma testemunha capinada e outra sem capina. As espécies de plantas daninhas mais freqüentes foram: Cenchrus echinatus L. (capim-carrapicho, Eleusine indica (L. Gaertn. (capim-pé-de-galinha e Brachiaria plantaginea (Link. Hitch. (capim-marmelada. Nenhum dos herbicidas testados apresento injúria à cultura. Quanto à produção, esses herbicidas apresentaram diferenças significativas em relação à testemunha capinada (828 kg/ha, sendo que o tratamento com clethodim + óleo mineral a 0,108 kg/ha + 0,5% v/v (528 kg/ha foi o único que apresentou diferenças significativas com a testemunha sem capina (330 kg/ha. Na altura da planta, a testemunha capinada somente apresentou diferenças significativas em relação ao tratamento com trifluralin e a testemunha sem capina. O carrapicho-de-burro e o capim-pé-de-galinha foram eficientemente controlados pelo clethodim + óleo mineral, em todas as doses estudadas, e sethoxydim + óleo mineral, com controle acima de 80% aos 45 dias da aplicação. O capim-marmelada foi eficientemente controlado pelo clethodim + óleo mineral a 0,096 e 0,108 kg/ha + 0,5% v/v, com 86% e 94%, respectivamente, seguido de sethoxydim + óleo mineral com 83%, e trifluralin com 71% de controle, até 45 dias após aplicação. O total de gramíneas foi eficientemente controlado pelo clethodim + óleo mineral 0,108 kg/ha + 0,5% v/v com 94,2% seguido de clethodim + óleo mineral 0,096 kg/ha + 0,5% v/v, com 85% e

  16. Field Dissipation and Storage Stability of Glufosinate Ammonium and Its Metabolites in Soil

    Directory of Open Access Journals (Sweden)

    Yun Zhang

    2014-01-01

    Full Text Available A simple analytical method was developed to measure concentrations of glufosinate ammonium and its metabolites, 3-methylphosphinico-propionic acid (MPP and 2-methylphosphinico-acetic acid (MPA, in field soil samples. To determine the minimum quantification limit, samples were spiked at different levels (0.1, 0.5, and 1.0 mg/kg. Soil samples were extracted with ammonium hydroxide solution 5% (v/v, concentrated, and reacted with trimethyl orthoacetate (TMOA in the presence of acetic acid for derivatization. The derivatives were quantified by gas chromatography (GC using a flame photometric detector (FPD. The linear correlation coefficients of glufosinate ammonium, MPP, and MPA in soil were 0.991, 0.999, and 0.999, respectively. The recoveries of this method for glufosinate ammonium, MPP, and MPA in soil were 77.2–95.5%, 98.3–100.3%, and 99.3–99.6% with relative standard deviations (RSD of 1.8–4.1%, 0.4–1.4%, and 1.3–2.0%, respectively. Glufosinate ammonium dissipated rapidly in soil to MPA in hours and gradually degraded to MPP. The half-life of glufosinate ammonium degradation in soil was 2.30–2.93 days in an open field. In soil samples stored at −20°C glufosinate ammonium was stable for two months. The results of this study should provide guidance for the safe application of the herbicide glufosinate ammonium to agricultural products and the environment.

  17. Field Dissipation and Storage Stability of Glufosinate Ammonium and Its Metabolites in Soil

    Science.gov (United States)

    Zhang, Yun; Wang, Kai; Wu, Junxue; Zhang, Hongyan

    2014-01-01

    A simple analytical method was developed to measure concentrations of glufosinate ammonium and its metabolites, 3-methylphosphinico-propionic acid (MPP) and 2-methylphosphinico-acetic acid (MPA), in field soil samples. To determine the minimum quantification limit, samples were spiked at different levels (0.1, 0.5, and 1.0 mg/kg). Soil samples were extracted with ammonium hydroxide solution 5% (v/v), concentrated, and reacted with trimethyl orthoacetate (TMOA) in the presence of acetic acid for derivatization. The derivatives were quantified by gas chromatography (GC) using a flame photometric detector (FPD). The linear correlation coefficients of glufosinate ammonium, MPP, and MPA in soil were 0.991, 0.999, and 0.999, respectively. The recoveries of this method for glufosinate ammonium, MPP, and MPA in soil were 77.2–95.5%, 98.3–100.3%, and 99.3–99.6% with relative standard deviations (RSD) of 1.8–4.1%, 0.4–1.4%, and 1.3–2.0%, respectively. Glufosinate ammonium dissipated rapidly in soil to MPA in hours and gradually degraded to MPP. The half-life of glufosinate ammonium degradation in soil was 2.30–2.93 days in an open field. In soil samples stored at −20°C glufosinate ammonium was stable for two months. The results of this study should provide guidance for the safe application of the herbicide glufosinate ammonium to agricultural products and the environment. PMID:25374604

  18. Fate of the herbicide glufosinate-ammonium in the sandy, low-organic-carbon aquifer at CFB Borden, Ontario, Canada

    Science.gov (United States)

    Allen-King, Richelle M.; Butler, Barbara J.; Reichert, Barbara

    1995-04-01

    The herbicide glufosinate-ammonium was persistent in aerobic sandy aquifer material in laboratory batch and field in situ microcosms when added at concentrations of 50-400 μg L -1. In contrast, the compound is biotransformed relatively quickly in surface soil. Glufosinate transformation and metabolite (3-methylphosphinyl-propionic acid) production in carbonamended laboratory microcosms demonstrated that the aquifer system was carbon-limited with respect to glufosinate transformation. Microbiological test showed that flufosinateammonium and sodium-glufosinate was be used as a nitrogen source, in the presence of sufficient carbon. Glufosinate was not used by the native microorganisms as a source of phosphorus, nor metabolized as a sole carbon and energy source. Ammonium appeared to be preferred over glufosinate as a nitrogen source. When representative microbial strains isolated from the Borden aquifer were tested, most were glufosinate-ammonium tolerant. Complete inhibition of some isolates was demonstrated only at very high concentrations of 2-4 g L -1. The research suggests that in an aquifer with a relatively low clay content and little labile organic carbon, such as the sandy aquifer at the field site, glufosinate will be persistent and transport will be essentially unretarded. The availability of alternative nitrogen sources was also indicated as a parameter that can affect persistence.

  19. Runoff of the herbicides triclopyr and glufosinate ammonium from oil palm plantation soil.

    Science.gov (United States)

    Tayeb, M A; Ismail, B S; Khairiatul-Mardiana, J

    2017-10-11

    This study focused on the residue detection of the herbicides triclopyr and glufosinate ammonium in the runoff losses from the Tasik Chini oil palm plantation area and the Tasik Chini Lake under natural rainfall conditions in the Malaysian tropical environment. Triclopyr and glufosinate ammonium are post-emergence herbicides. Both herbicides were foliar-sprayed on 0.5 ha of oil palm plantation plots, which were individualized by an uneven slope of 10-15%. Samples were collected at 1, 3, 7, 15, 30, 45, 60, 90, and 120 days after treatment. The concentrations of both herbicides quickly diminished from those in the analyzed sample by the time of collection. The highest residue levels found in the field surface leachate were 0.031 (single dosage, triclopyr), 0.041 (single dosage, glufosinate ammonium), 0.017 (double dosage, triclopyr), and 0.037 μg/kg (double dosage, glufosinate ammonium). The chromatographic peaks were observed at "0" day treatment (2 h after herbicide application). From the applied active ingredients, the triclopyr and glufosinate losses were 0.025 and 0.055%, respectively. The experimental results showed that both herbicides are less potent than other herbicides in polluting water systems because of their short persistence and strong adsorption onto soil clay particles.

  20. Developmental and dysmorphogenic effects of glufosinate ammonium on mouse embryos in culture.

    Science.gov (United States)

    Watanabe, T; Iwase, T

    1996-01-01

    The effects of glufosinate ammonium on embryonic development in mice were examined using whole embryo and micromass cultures of midbrain and limb bud cells. In day 8 embryos cultured for 48 hr, glufosinate caused significant overall embryonic growth retardation and increased embryolethality to 37.5% at 10 micrograms/ml (5.0 x 10(-5) M). All embryos in the treated groups exhibited specific morphological defects including hypoplasia of the prosencephalon (forebrain) (100%) and visceral arches (100%). In day 10 embryos cultured for 24 hr, glufosinate significantly reduced the crown-rump length and the number of somite pairs, and produced a high incidence of morphological defects (84.6%) at 10 micrograms/ml. These embryos were characterized by blister in the lateral head (100%), hypoplasia of prosencephalon (57.1%), and cleft lips (42.9%) at 20 micrograms/ml (10.0 x 10(-5) M). Histological examination of the treated embryos showed numerous cell death (pyknotic debris) present throughout the neuroepithelium in the brain vesicle and neural tube, but did not involve the underlying mesenchyme. In micromass culture, glufosinate inhibited the differentiation of midbrain cells in day 12 embryos with 50% inhibition occurring at 0.55 microgram/ml (2.8 x 10(-6) M). The ratios of 50% inhibition concentration for cell proliferation to cell differentiation in limb bud cells were 0.76 and 1.52 in day 11 and 12 embryos, respectively. These findings indicate that glufosinate ammonium is embryotoxic in vitro. In addition to causing growth retardation, glufosinate specifically affected the neuroepithelium of the brain vesicle and neural tube, leading to neuroepithelial cell death.

  1. Serial ammonia measurement in patients poisoned with glufosinate ammonium herbicide.

    Science.gov (United States)

    Moon, J M; Chun, B J

    2016-05-01

    This study investigated whether ammonia concentrations can predict delayed neurotoxicity development and neurotoxicity latency in glufosinate ammonium (GLA) herbicide-poisoned patients presenting with an alert mental state and stable hemodynamics. This retrospective observational case study included 26 patients divided into 2 groups: neurotoxicity during hospitalization (complicated group) and without neurotoxicity (noncomplicated group). Thirteen patients (50.0%) experienced neurotoxicity at 16 h post-ingestion. Although ammonia concentrations at presentation did not differ significantly between the two groups, the ammonia level in the complicated group increased significantly at the next measurement and remained significantly higher than that in the noncomplicated group until 48 h after ingestion. The peak ammonia concentration before neurotoxicity development was an independent predictor of neurotoxicity (odds ratio: 1.047, 95% confidence interval: 1.010-1.087, p value = 0.014), and the optimal cutoff value of peak ammonia concentration for predicting neurotoxicity was 101.5 μg/dL. The rate of ammonia increase was not associated with the time latency from ingestion to neurotoxicity development. This study showed that serial ammonia measurements in GLA-poisoned patients may identify those who are at high risk of developing neurotoxicity. However, as this study enrolled few patients, further qualified trials are required to confirm our results and to reveal the etiology of hyperammonemia and its causality in neurotoxicity. © The Author(s) 2015.

  2. Two cases of glufosinate poisoning with late onset convulsions.

    Science.gov (United States)

    Tanaka, J; Yamashita, M; Yamashita, M; Matsuo, H; Yamamoto, T

    1998-08-01

    Glufosinate ammonium (GLA), the active ingredient in the non-selective herbicide BASTA (18.5% GLA), is a phosphinic acid analogue of glutamic acid. We report 2 cases of GLA poisoning with late onset convulsions and increased serum CK in spite of low blood concentrations of GLA after hemodialysis. A 69-y-old female was admitted to the emergency department after taking 500 ml of BASTA. On arrival she was conscious, and gut decontamination, hemodialysis and hemoperfusion were performed. However, 8 1/2 hours after ingestion, general convulsions occurred. Her serum OK increased to a peak of 24,900 IU/L on the third day of admission. An 87-y-old male was admitted to the emergency department 3 1/2 hours after taking 200 ml of BASTA and receiving gastric lavage at a local emergency room. On arrival he was conscious, and serial activated charcoal and hemodialysis was performed. Blood concentration of GLA after hemodialysis decreased from 1.56 micrograms/ml to 0.68 micrograms/ml. Thirty hours after admission he had general convulsions. GLA was not detected in the cerebrospinal fluid 6 h after the convulsions. His serum CK increased to a peak of 17,870 IU/L on the fifth day of admission.

  3. Bacterial Associations: Antagonism to Symbiosis

    Digital Repository Service at National Institute of Oceanography (India)

    Nair, S.

    mutualism through commensalisms and competition, to antagonism, determined ultimately by balancing the cost of the association against the benefits received (Pianka, 1994). A continuum can be envisioned that spans a dynamic bridge from antagonism... when two organisms form a relationship, which provides an advantage for both the partners at least temporarily. In commensalisms only one partner derives benefit and the other does not. Symbiosis The word, ?symbiosis? is derived from the Greek word...

  4. Insecticidal activity of glufosinate through glutamine depletion in a caterpillar.

    Science.gov (United States)

    Kutlesa, N J; Caveney, S

    2001-01-01

    The herbicide glufosinate-ammonium (GLA) is a competitive inhibitor of glutamine synthetase (GS), an enzyme converting glutamate to glutamine in both plants and animals. Because GS is essential for ammonia detoxification in plants, GLA treatment disrupts photorespiration by causing a build-up of ammonia and a loss of glutamine in plant tissues. This study reports that GLA applied to leaf surfaces is also toxic to 5th-instar caterpillars of the skipper butterfly Calpodes ethlius (LD50 = 400 mg kg-1). After ingesting GLA, caterpillars stopped feeding and became dehydrated through a loss of rectal function. Caterpillars showed symptoms of neurotoxicity, such as proleg tremors, body convulsions and complete paralysis before death. Incubation of several tissues isolated from normal feeding-stage caterpillars with the GS substrates glutamate and ammonium showed that GLA inhibited GS activity in vitro. Within 24 h of ingesting GLA, caterpillars had a greatly reduced glutamine content and the ammonium ion levels had more than doubled. Injection of ammonium chloride into non-GLA-treated caterpillars had no deleterious effect, suggesting that glutamine depletion, and not a rise in body ammonium, was the primary cause of GLA toxicity following GS inhibition. This was supported by the observation that the onset of the symptoms of GLA poisoning could be postponed by giving GLA-fed caterpillars several subsequent daily injections of glutamine. The effective GLA dose fed to 5th-instar caterpillars in this study was comparable to the amount that might realistically by acquired from feeding on GLA-treated crops.

  5. Comparison of the effectiveness of Basta, Bialaphos and Glufosinate Ammonium for selecting Transformed Oil Palm Tissues

    International Nuclear Information System (INIS)

    A Rahman Nurfahisza; Md Aman Rafiqah; Ghulam Kadir Ahmad Parveez; Omar Abdul Rashid

    2016-01-01

    One of the important requirements for producing transgenic plants is the ability to isolate true transformed cells and regenerate into complete plants without chimera and escapes. Therefore, an efficient selection process is essential. In this study, three different selection agents, namely Basta, bialaphos and glufosinate ammonium were evaluated on embryogenic calli and embryoids, for their effectiveness on selecting transformed oil palm tissues. Un transformed tissues were used in this study as the minimal concentrations which inhibit the growth of the tissues would be the optimum concentrations for selecting the transformed cells. Based on this study, the growth of embryogenic calli was shown to be fully inhibited at 10 mg litre -1 of Basta. Meanwhile, only 3 mg litre -1 of bialaphos and glufosinate ammonium are needed to inhibit the embryogenic calli. For oil palm embryo id cultures, the minimal concentration for Basta was determined at 20 mg litre -1 as compared to 5 mg litre -1 for bialaphos and glufosinate ammonium. This result indicated that a higher concentration of Basta is needed to completely inhibit the growth of oil palm tissues as compared to bialaphos and glufosinate ammonium. Furthermore, these observations revealed that embryogenic calli are more sensitive to the three selection agents as compared to embryoids. The information gained from this study will be used as a guideline to increase the efficiency for selecting transformed oil palm cells and producing transgenic oil palm. (author)

  6. VARIATION IN THE SENSITIVITY OF WANDERING JEW PLANTS TO GLUFOSINATE AMMONIUM

    Directory of Open Access Journals (Sweden)

    IVANA PAULA FERRAZ SANTOS DE BRITO

    2017-01-01

    Full Text Available This study aimed to identify the response of wandering jew (Commelina benghalensis L. plants to different doses of glufosinate ammonium and the sensitivity of plants populations to the herbicide. Two studies were conducted, both in a greenhouse, and were repeated at different times. In the first study, two experiments were conducted to examine the dose-response curve using seven different doses of the glufosinate ammonium herbicide (0, 50, 100, 200, 400, 800, and 1600 g a.i. ha-1 with four replicates each. In the second study, which examined the range in sensitivity of wandering jew plants to glufosinate ammonium, 26 plants were sprayed with a dose of 200 g a.i. ha-1 herbicide. Visual assessments of percent injury and measurements of leaf tissue ammonium content were conducted. The use of untreated wandering jew control plants allowed for the correlation of glufosinate ammonium treatment with the ammonium concentrations in treated plant tissues; the ammonium concentration increased as a function of herbicide application, albeit not linearly with the dose. Ammonium content varied among individuals of the wandering jew plant population.

  7. Analysis of reproductive toxicity and classification of glufosinate-ammonium.

    Science.gov (United States)

    Schulte-Hermann, Rolf; Wogan, Gerald N; Berry, Colin; Brown, Nigel A; Czeizel, Andrew; Giavini, Erminio; Holmes, Lewis B; Kroes, Robert; Nau, Heinz; Neubert, Diether; Oesch, Franz; Ott, Tilmann; Pelkonen, Olavi; Robert-Gnansia, Elisabeth; Sullivan, Frank M

    2006-04-01

    CONCLUSION REGARDING CLASSIFICATION OF GLUFOSINATE-AMMONIUM: Science Partners' Evaluation Group (Evaluation Group) has conducted an independent analysis of the herbicide glufosinate-ammonium (GA) relative to its potential to cause reproductive toxicity in humans. Further, the Evaluation Group has evaluated the implementation of Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC) and Council Directive 91/414/EEC, with respect to classification of chemicals posing potential reproductive hazards. After consideration of all information available to us relevant to the potential of glufosinate-ammonium (GA) to cause reproductive toxicity, the Science Partners Evaluation Group concludes that no classification of GA is justified. The following form the basis of this conclusion. There are no human data to suggest that GA causes reproductive toxicity in women or in their conceptus. The issue concerning possible reproductive hazard to humans is raised solely on the basis of positive animal test results that show GA to cause preimplantation or implantation losses in rats. SPECIFICALLY: a. Daily treatment with GA had no detectable effect on the earliest stages of the reproductive sequence including gametogenesis, ovulation, mating and conception; b. Treatment with GA interfered with rat gestation before and at the stage when the conceptus implants into the uterus. This effect occurred at doses of 360 ppm in the feed (corresponding to daily doses of 27.8 mg/kg bw) and above; and c. After implantation, no further effect of GA on prenatal and post-natal development was recognized. Previous concerns that GA might be toxic to embryonic stages after implantation were not supported by the data. Abortions and stillbirth seen were associated with, and regarded as secondary to, maternal toxicity. There was no evidence suggesting the induction of malformations in the offspring. The mechanism underlying this adverse effect in experimental laboratory

  8. Effects of soil phosphorus status on environmental risk assessment of glyphosate and glufosinate-ammonium.

    Science.gov (United States)

    Laitinen, Pirkko; Siimes, Katri; Rämö, Sari; Jauhiainen, Lauri; Eronen, Liisa; Oinonen, Seija; Hartikainen, Helinä

    2008-01-01

    The increased use of herbicides poses a risk to the aquatic environment. Easy and economical methods are needed to identify the fields where specific environment protection measures are needed. Phosphorus (P) and organophosphorus herbicides compete for the same adsorption sites in soil. In this study the relationship between P obtained in routine Finnish agronomic tests (acid ammonium acetate [P(AC)]) and adsorption of glyphosate and glufosinate-ammonium was investigated to determine whether P(AC) values could be used in the risk assessment. The adsorption of glyphosate ((N-(phosphonomethyl)glycine) and glufosinate-ammonium (2-amino-4-(hydroxymethylphosphinyl)butanoic acid) was studied in a clay and a sandy loam soil enriched with increasing amounts of P added as potassium dihydrogen phosphate. Desorption was also determined for some P-enriched soil samples. The adsorption of both herbicides diminished with increasing P(AC) value. The correlations between Freundlich adsorption coefficients obtained in the adsorption tests and P(AC) were nonlinear but significant (r > 0.98) in both soils. The exponential models of the relationship between soil P(AC) values and glyphosate adsorption were found to fit well to an independent Finnish soil data set (P glufosinate-ammonium). The desorption results showed that glufosinate-ammonium sorption is not inversely related to soil P status, and the high correlation coefficients obtained in the test of the model were thus artifacts caused by an abnormal concentration of exchangeable potassium in soil. The solved equations are a useful tool in assessing the leaching risks of glyphosate, but their use for glufosinate-ammonium is questionable.

  9. Effects of glufosinate on antioxidant enzymes, subcellular structure, and gene expression in the unicellular green alga Chlorella vulgaris.

    Science.gov (United States)

    Qian, Haifeng; Chen, Wei; Sheng, G Daniel; Xu, Xiaoyan; Liu, Weiping; Fu, Zhengwei

    2008-07-30

    Greater exposure to herbicide increases the likelihood of harmful effects in humans and the environment. Glufosinate, a non-selective herbicide, inhibits glutamine synthetase (GS) and thus blocks ammonium assimilation in plants. In the present study, the aquatic unicellular alga Chlorella vulgaris was chosen to assess the effects of acute glufosinate toxicity. We observed physiological changes during 12-96 h of exposure, and gene transcription during 6-48 h of exposure. Exposure to glufosinate increased malondialdehyde content by up to 2.73 times compared with the control, suggesting that there was some oxidative damage. Electron microscopy also showed that there were some chloroplast abnormalities in response to glufosinate. The activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) also increased markedly in the presence of glufosinate. Maximum activities of SOD, POD, and CAT were 2.90, 2.91, and 2.48 times that of the control, respectively. These elevated activities may help alleviate oxidative damage. A real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL. The results showed that glufosinate reduced the transcript abundances of the three genes after 12h exposure. The lowest abundances of psaB, psbC and rbcL transcripts in response to glufosinate exposure were 38%, 16% and 43% of those of the control, respectively. Our results demonstrate that glufosinate affects the activities of antioxidant enzymes, disrupts chloroplast ultrastructure, and reduces transcription of photosynthesis-related genes in C. vulgaris.

  10. Takotsubo Cardiomyopathy as a Delayed Complication with a Herbicide Containing Glufosinate Ammonium in a Suicide Attempt: A Case Report

    OpenAIRE

    Tominaga, Keiichiro; Izumi, Manabu; Suzukawa, Masayuki; Shinjo, Takafumi; Izawa, Yoshimitsu; Yonekawa, Chikara; Ano, Masaki; Yamashita, Keisuke; Muronoi, Tomohiro; Mochiduki, Reiko

    2012-01-01

    Background. Glufosinate ammonium has a famous delayed complication as respiratory failure, however, delayed cardiogenic complication is not well known. Objectives. The aim of this study is to report a takotsubo cardiomyopathy as a delayed complication of glufosinate ammonium for suicide attempt. Case Report. A 75-year-old woman ingested about 90 mL of Basta, herbicide for suicide attempt at arousal during sleep. She came to our hospital at twelve hours after ingesting. She was admitted to our...

  11. Effects of glufosinate on antioxidant enzymes, subcellular structure, and gene expression in the unicellular green alga Chlorella vulgaris

    International Nuclear Information System (INIS)

    Qian Haifeng; Chen Wei; Sheng, G. Daniel; Xu Xiaoyan; Liu Weiping; Fu Zhengwei

    2008-01-01

    Greater exposure to herbicide increases the likelihood of harmful effects in humans and the environment. Glufosinate, a non-selective herbicide, inhibits glutamine synthetase (GS) and thus blocks ammonium assimilation in plants. In the present study, the aquatic unicellular alga Chlorella vulgaris was chosen to assess the effects of acute glufosinate toxicity. We observed physiological changes during 12-96 h of exposure, and gene transcription during 6-48 h of exposure. Exposure to glufosinate increased malondialdehyde content by up to 2.73 times compared with the control, suggesting that there was some oxidative damage. Electron microscopy also showed that there were some chloroplast abnormalities in response to glufosinate. The activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) also increased markedly in the presence of glufosinate. Maximum activities of SOD, POD, and CAT were 2.90, 2.91, and 2.48 times that of the control, respectively. These elevated activities may help alleviate oxidative damage. A real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL. The results showed that glufosinate reduced the transcript abundances of the three genes after 12 h exposure. The lowest abundances of psaB, psbC and rbcL transcripts in response to glufosinate exposure were 38%, 16% and 43% of those of the control, respectively. Our results demonstrate that glufosinate affects the activities of antioxidant enzymes, disrupts chloroplast ultrastructure, and reduces transcription of photosynthesis-related genes in C. vulgaris

  12. Effects of glufosinate on antioxidant enzymes, subcellular structure, and gene expression in the unicellular green alga Chlorella vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Qian Haifeng; Chen Wei; Sheng, G. Daniel; Xu Xiaoyan; Liu Weiping [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Fu Zhengwei [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China)], E-mail: azwfu2003@yahoo.com.cn

    2008-07-30

    Greater exposure to herbicide increases the likelihood of harmful effects in humans and the environment. Glufosinate, a non-selective herbicide, inhibits glutamine synthetase (GS) and thus blocks ammonium assimilation in plants. In the present study, the aquatic unicellular alga Chlorella vulgaris was chosen to assess the effects of acute glufosinate toxicity. We observed physiological changes during 12-96 h of exposure, and gene transcription during 6-48 h of exposure. Exposure to glufosinate increased malondialdehyde content by up to 2.73 times compared with the control, suggesting that there was some oxidative damage. Electron microscopy also showed that there were some chloroplast abnormalities in response to glufosinate. The activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) also increased markedly in the presence of glufosinate. Maximum activities of SOD, POD, and CAT were 2.90, 2.91, and 2.48 times that of the control, respectively. These elevated activities may help alleviate oxidative damage. A real-time polymerase chain reaction (PCR) assay showed changes in transcript abundances of three photosynthetic genes, psaB, psbC, and rbcL. The results showed that glufosinate reduced the transcript abundances of the three genes after 12 h exposure. The lowest abundances of psaB, psbC and rbcL transcripts in response to glufosinate exposure were 38%, 16% and 43% of those of the control, respectively. Our results demonstrate that glufosinate affects the activities of antioxidant enzymes, disrupts chloroplast ultrastructure, and reduces transcription of photosynthesis-related genes in C. vulgaris.

  13. Resistance to glufosinate is proportional to phosphinothricin acetyltransferase expression and activity in LibertyLink(®) and WideStrike(®) cotton.

    Science.gov (United States)

    Carbonari, Caio A; Latorre, Débora O; Gomes, Giovanna L G C; Velini, Edivaldo D; Owens, Daniel K; Pan, Zhiqiang; Dayan, Franck E

    2016-04-01

    Insertion of the gene encoding phosphinothricin acetyltransferase (PAT) has resulted in cotton plants resistant to the herbicide glufosinate. However, the lower expression and commensurate reduction in PAT activity is a key factor in the low level of injury observed in the WideStrike(®) cotton and relatively high level of resistance observed in LibertyLink(®) cotton. LibertyLink(®) cotton cultivars are engineered for glufosinate resistance by overexpressing the bar gene that encodes phosphinothricin acetyltransferase (PAT), whereas the insect-resistant WideStrike(®) cultivars were obtained using the similar pat gene as a selectable marker. The latter cultivars carry some level of resistance to glufosinate which enticed certain farmers to select this herbicide for weed control with WideStrike(®) cotton. The potency of glufosinate on conventional FM 993, insect-resistant FM 975WS, and glufosinate-resistant IMACD 6001LL cotton cultivars was evaluated and contrasted to the relative levels of PAT expression and activity. Conventional cotton was sensitive to glufosinate. The single copy of the pat gene present in the insect-resistant cultivar resulted in very low RNA expression of the gene and undetectable PAT activity in in vitro assays. Nonetheless, the presence of this gene provided a good level of resistance to glufosinate in terms of visual injury and effect on photosynthetic electron transport. The injury is proportional to the amount of ammonia accumulation. The strong promoter associated with bar expression in the glufosinate-resistant cultivar led to high RNA expression levels and PAT activity which protected this cultivar from glufosinate injury. While the insect-resistant cultivar demonstrated a good level of resistance to glufosinate, its safety margin is lower than that of the glufosinate-resistant cultivar. Therefore, farmers should be extremely careful in using glufosinate on cultivars not expressly designed and commercialized as resistant to this

  14. Seletividade de amonio-glufosinate isolado e em mistura com pyrithiobac-sodium em algodoeiro transgênico LL® Selectivity of ammonium-glufosinate applied alone or in mixture with pyrithiobac sodium in transgenic LL® cotton

    Directory of Open Access Journals (Sweden)

    G.B.P. Braz

    2012-12-01

    Full Text Available Com a recente introdução no Brasil de variedades transgênicas de algodoeiro que apresentam resistência ao amonio-glufosinate (LL®, há escassez de informações tanto a respeito da seletividade de reaplicações desse herbicida, quanto no que se refere a misturas com outros herbicidas. Objetivou-se no presente trabalho avaliar a seletividade de aplicações sequenciais de amonio-glufosinate isolado e em associação com pyrithiobac-sodium em algodão transgênico LL®. Dessa forma, foi instalado um experimento em delineamento de blocos casualizados em arranjo fatorial (3x3+1, empregando-se oito repetições. O primeiro fator correspondeu à aplicação dos tratamentos amonio-glufosinate (500 g ha-1 e amonio-glufosinate + pyrithiobac-sodium (500 + 42 g ha-1 e 500 + 56 g ha-1. O segundo fator foi o número de aplicações sequenciais em pós-emergência do algodoeiro (uma, duas ou três. O tratamento adicional foi composto por testemunha sem aplicação de herbicida. A associação do pyrithiobac-sodium ao amonio-glufosinate causou maiores níveis de fitointoxicação inicial, embora não tenham havido mais sintomas duas semanas após as aplicações. A qualidade de fibra do algodoeiro não foi influenciada por nenhum dos tratamentos herbicidas. O amonio-glufosinate isolado foi seletivo para o algodão LL® em até três aplicações em pós-emergência. O algodoeiro apresentou ainda tolerância a uma aplicação da mistura de amonio-glufosinate + pyrithiobac-sodium, e não se observou qualquer efeito negativo sobre a produtividade de algodão em caroço.Due to the recent introduction of transgenic cotton varities with resistance to ammonium-glufosinate (LL® in Brazil, there is a lack of information related both to the selectivity of sequential reapplications of ammonium-glufosinate and to tank mixture with other herbicides. This work aimed to evaluate the selectivity of sequential applications of ammonium-glufosinate isolated or in

  15. Interaction of 2,4-D or Dicamba with Glufosinate for Control of Glyphosate-Resistant Giant Ragweed (Ambrosia trifida L. in Glufosinate-Resistant Maize (Zea mays L.

    Directory of Open Access Journals (Sweden)

    Zahoor A. Ganie

    2017-07-01

    Full Text Available Glyphosate-resistant (GR giant ragweed is a problematic broadleaf weed in crops including maize and soybean in the Midwestern United States. Commercialization of crops with 2,4-D or dicamba and glufosinate resistance will allow post-emergence (POST applications of these herbicides. Therefore, information is needed on how 2,4-D/dicamba will interact with glufosinate in various rate combinations. The objectives of this study were to evaluate the interaction of glufosinate plus 2,4-D and/or dicamba for control of GR giant ragweed, and to determine their effect on GR giant ragweed density, biomass, maize injury, and yield. Field experiments were conducted in 2013 and 2014 in a field infested with GR giant ragweed in Nebraska, United States. The treatments included POST applications of glufosinate (450 or 590 g ai ha-1, 2,4-D, or dicamba at 280 or 560 g ae ha-1 applied alone and in tank-mixtures in glufosinate-resistant maize. The results showed that dicamba applied alone resulted in 56 to 62% and 73 to 83% control at 14 and 28 days after treatment (DAT, respectively, and ≥95% control at 60 DAT or at harvest compared to 17 to 30% and 57 to 73% control with 2,4-D applied alone at 280 and 560 g ai ha-1, respectively. Glufosinate tank-mixed with 2,4-D and/or dicamba consistently provided ≥89% control of GR giant ragweed, except that control with glufosinate plus 2,4-D varied from 80 to 92% at 60 DAT and at harvest. The comparison between the observed and expected control (determined by Colby’s equation suggested an additive interaction between glufosinate and 2,4-D or dicamba for control of GR giant ragweed. Contrast analysis also indicated that GR giant ragweed control with glufosinate plus 2,4-D or dicamba was either consistently higher or comparable with individual herbicides excluding 2,4-D applied alone. Herbicide programs, excluding 2,4-D at 280 g ae ha-1, resulted in ≥80% reduction in GR giant ragweed density. Tank-mixing glufosinate with

  16. Dose reduzida de clethodim no controle de papua na cultura da soja, em função da época de aplicação Reduced rate of clethodim for alexandergrass: control in soybeans as a function of application time

    Directory of Open Access Journals (Sweden)

    Nilson G. Fleck

    1997-01-01

    Full Text Available Foi realizado um experimento a campo em Eldorado do Sul, RS, no ano agrícola de 19 94 /9 5, para avaliar o controle de papuã (Brachiaria plantaginea (Linck Hitchc., que ocorreu numa população média de 95 plantas/m2. Foi avaliado o herbicida clethodim à dose-plena (120g/ ha e à meia-dose (60g/ha. A cultivar de soja utilizada foi RS-7 Jacuí e usado o delineamento experimental em blocos casualizados com quatro repetições. Os tratamentos foram aplicados aos 14, 21, 28 e 35 dias após a emergência da soja (DAE. Foram mantidas testemunhas capinadas, com operações iniciadas nas mesmas épocas de aplicação do herbicida, e uma testemunha infestada durante todo o ciclo da cultura. O controle foi avaliado visualmente, em três ocasiões, através de escala percentual. Os graus de controle de papua obtidos à dose-plena foram equivalentes entre si quando aplicado nas três primeiras épocas, com eficiência entre 95 e 98% na última avaliação. A meia-dose mostrou, para as três primeiras épocas de aplicação, resultados semelhantes aos de doseplena, porém em níveis um pouco inferiores, situando-se entre 85 e 95% o controle obtido na última avaliação. O controle do papuã foi mediano quando clethodim foi aplicado aos 35 DAE, tanto par a dose-plena quanto para meiadose. Quanto ao rendimento de grãos, não houve diferença estatística significativa entre os tratamentos em suas várias modalidades, embora todos tenham superado a testemunha infestada, com incrementos na produtividade de grãos entre 73 e 10 5% . O experimento permite concluir pela viabilidade da utilização de meiadose de clethodim para o controle de papua em soja, realizando as aplicações preferencialmente até a quarta semana após a emergência da cultura.A field trial was carried out in Eldorado do Sul, RS, during the 1994/95 growing season to evaluate Alexandergrass (Brachiaria plantaginea (Linck Hitchc control, that occurred with na average population of 95

  17. Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium.

    Science.gov (United States)

    Park, S; Kim, D E; Park, S Y; Gil, H W; Hong, S Y

    2018-04-01

    The incidence and clinical aspects of seizures remain to be elucidated in patients with acute pesticide intoxication. The present study included subjects who ingested pesticide with the intention of committing suicide and were treated at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and December 2014. We analyzed the incidence and characterized the type and frequency of seizure, from the medical records of 464 patients with acute pesticide intoxication, according to the pesticide class. The effect of seizure on the clinical outcome was assessed. The incidence of seizure was 31.5% in patients who ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl] butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after seizure initiation, following treatment with antiseizure medication. Generalized tonic-clonic seizures were the most commonly observed (85.7% of the cases). Multivariable logistic regression analysis showed that the effect of seizure on mortality was not statistically significant. In conclusion, glufosinate ammonium herbicide is the most common seizurogenic pesticide class. Seizure itself was not a risk factor for mortality in patients with acute glufosinate ammonium intoxication.

  18. The effect of several adjuvants on glufosinate effectiveness in Conyza species.

    Science.gov (United States)

    Fernandez-Cerejido, M C; Bastida, F; Menendez, J

    2009-01-01

    The effect of several adjuvants on the effectiveness of glufosinate and the role of adherence and contact angle modifications due to the presence of these adjuvants in the spraying solution on the increase in efficacy observed on the broadleaved weeds Conyza albida and Conyza bonariensis has been determined under laboratory controlled conditions. The adjuvants used on the experiment were a mixture of methyl oleate and palmitate (MO/MP), a dodecylbenzene ammonium sulphonate (DBAS), a paraffinic oil (PO), an alkylglycol ester (AGE), and a lecithin + propionic acid + non ionic surfactant based product (LI-700). Dose-response experiments showed that C. albida displayed higher susceptibility to glufosinate than C. bonariensis, no matter the adjuvant tested. However, none of the mixtures increased the herbicide effectiveness on C. atlbida, with LI 700 and PO showing an antagonistic effect on the herbicide efficacy. On C. bonariensis, MO/MP and DBAS showed significant better results than non-amended glufosinate controls, with LI 700 showing again an antagonistic effect. Both adherence and contact angle studies were inconclusive, since adjuvants with best adherence and contact angle values were not the most effective ones. Therefore, other unknown parameters putatively modified by adjuvants such as herbicide penetration should be questioned.

  19. Effects of glufosinate-ammonium on off crop vegetation--interim results.

    Science.gov (United States)

    De Snoo, G R; De Jong, F M; Van Der Poll, R J; Van Der Linden, M G

    2001-01-01

    In 2000 a field study was conducted at four different locations concerning the effects of low dosages of glufosinate-ammonium, a leaf acting herbicide, on off crop vegetation. Therefore species rich road verges and ditch banks not adapted to a history of herbicide use were sprayed twice with different dosages of glufosinate-ammonium, simulating drift (0, 2, 4, 16, 32 and 64% of the maximum field dose: 800 g a.i./ha). The parameters studied were short term phytotoxic effects and the effects on biomass, species cover and number of species in autumn (Braun-Blanquêt relevés). The results show significant phytotoxic effects at all dosages of glufosinate-ammonium on the non-target vegetation. The low concentrations (2 and 4%) had most impact when applied early in the season (9% average at the 2% dosage and 22% at 4% dosage, after the first spraying. At high dosages (32 and 64%) a decrease of the biomass of the vegetation was found in August. A comparison between treatments in August shows a small decrease in species number and cover in the 64% compared to the control. In the comparison between the spring and August relevés, the decrease in the mean number of species was significantly stronger in the treated plots than in the untreated ones of 4% and higher. For monocotyledons in all treatments except 16%, a significantly stronger decrease in species number was found compared to the untreated. For dicotyledons only the 64% dosage differed from the untreated. Only at the 64% treatment the total cover of species decreased more than in the untreated plots. Since drift percentages of 2-4% can be expected at 1-2 m from a treated plot it can be concluded that the use of glufosinate-ammonium could result in visible short term phytotoxic effects (max 22%) on off-crop vegetation such as ditch banks and verges. There are also indications that effects on the number and cover of species in autumn can occur. Because in future glufosinate-ammonium could be used on a large scale in

  20. The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study.

    Science.gov (United States)

    Cha, Y S; Kim, H; Lee, Y; Choi, E H; Kim, H I; Kim, O H; Cha, K-C; Lee, K H; Hwang, S O

    2018-06-01

    Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient's presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 μg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

  1. Forward selection for multiple resistance across the non-selective glyphosate, glufosinate and oxyfluorfen herbicides in Lolium weed species.

    Science.gov (United States)

    Fernández, Pablo; Alcántara, Ricardo; Osuna, María D; Vila-Aiub, Martin M; Prado, Rafael De

    2017-05-01

    In the Mediterranean area, Lolium species have evolved resistance to glyphosate after decades of continual use without other alternative chemicals in perennial crops (olive, citrus and vineyards). In recent years, oxyfluorfen alone or mixed with glyphosate and glufosinate has been introduced as a chemical option to control dicot and grass weeds. Dose-response studies confirmed that three glyphosate-resistant Lolium weed species (L. rigidum, L. perenne, L. multiflorum) collected from perennial crops in the Iberian Peninsula have also evolved resistance to glufosinate and oxyfluorfen herbicides, despite their recent introduction. Based on the LD 50 resistance parameter, the resistance factor was similar among Lolium species and ranged from 14- to 21-fold and from ten- to 12-fold for oxyfluorfen and glufosinate respectively. Similarly, about 14-fold resistance to both oxyfluorfen and glufosinate was estimated on average for the three Lolium species when growth reduction (GR 50 ) was assessed. This study identified oxyfluorfen resistance in a grass species for the first time. A major threat to sustainability of perennial crops in the Iberian Peninsula is evident, as multiple resistance to non-selective glyphosate, glufosinate and oxyfluorfen herbicides has evolved in L. rigidum, L. perenne and L. multiflorum weeds. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  2. Metabolism of the herbicide glufosinate-ammonium in plant cell cultures of transgenic (rhizomania-resistant) and non-transgenic sugarbeet (Beta vulgaris), carrot (Daucus carota), purple foxglove (Digitalis purpurea) and thorn apple (Datura stramonium).

    Science.gov (United States)

    Müller, B P; Zumdick, A; Schuphan, I; Schmidt, B

    2001-01-01

    The metabolism of the herbicide glufosinate-ammonium was investigated in heterotrophic cell suspension and callus cultures of transgenic (bar-gene) and non-transgenic sugarbeet (Beta vulgaris). Similar studies were performed with suspensions of carrot (Daucus carota), purple foxglove (Digitalis purpurea) and thorn apple (Datura stramonium). 14C-labelled chemicals were the (racemic) glufosinate, L-glufosinate, and D-glufosinate, as well as the metabolites N-acetyl L-glufosinate and 3-(hydroxymethylphosphinyl)propionic acid (MPP). Cellular absorption was generally low, but depended noticeably on plant species, substance and enantiomer. Portions of non-extractable residues ranged from 0.1% to 1.2% of applied 14C. Amounts of soluble metabolites resulting from glufosinate or L-glufosinate were between 0.0% and 26.7% of absorbed 14C in non-transgenic cultures and 28.2% and 59.9% in transgenic sugarbeet. D-Glufosinate, MPP and N-acetyl L-glufosinate proved to be stable. The main metabolite in transgenic sugarbeet was N-acetyl L-glufosinate, besides traces of MPP and 4-(hydroxymethylphosphinyl)butanoic acid (MPB). In non-transgenic sugarbeet, glufosinate was transformed to a limited extent to MPP and trace amounts of MPB. In carrot, D stramonium and D purpurea, MPP was also the main product; MPB was identified as a further trace metabolite in D stramonium and D purpurea.

  3. Selectivity of ammonium-glufosinate applied alone or in mixture with pyrithiobac sodium in transgenic LL® cotton

    OpenAIRE

    Braz, G.B.P.; Oliveira Jr, R.S.; Constantin, J.; Raimondi, M.A.; Franchini, L.H.M.; Biffe, D.F.; Arantes, J.G.Z.; Takano, H.K.

    2012-01-01

    Com a recente introdução no Brasil de variedades transgênicas de algodoeiro que apresentam resistência ao amonio-glufosinate (LL®), há escassez de informações tanto a respeito da seletividade de reaplicações desse herbicida, quanto no que se refere a misturas com outros herbicidas. Objetivou-se no presente trabalho avaliar a seletividade de aplicações sequenciais de amonio-glufosinate isolado e em associação com pyrithiobac-sodium em algodão transgênico LL®. Dessa forma, foi instalado um expe...

  4. Vasogenic edema in striatum following ingestion of glufosinate-containing herbicide.

    Science.gov (United States)

    Lee, Hui-Young; Song, Seo-Young; Lee, Seung-Hwan; Lee, Seo-Young; Kim, Sung-Hun; Ryu, Sook-Won

    2009-10-01

    Glufosinate-ammonium (GLA) is a broad-spectrum herbicide used worldwide. We report a patient who attempted suicide by ingesting a liquid herbicide containing GLA. A diffusion-weighted MRI showed cytotoxic edema in the hippocampus as well as vasogenic edema in the striata. To our knowledge, vasogenic edema caused by GLA-containing herbicide involving the striatum has not been reported in association with cytotoxic edema in the hippocampus. We assume that this herbicide affected the central nervous system via different mechanisms to produce both cytotoxic and vasogenic edema in the same patient.

  5. Sensitivity to Glufosinate-ammonium herbicide in plants of Glycine max cultivar INCASoy-27

    Directory of Open Access Journals (Sweden)

    Jorge Liusvert Pérez Pérez

    2014-10-01

    Full Text Available This work had as objective to define the minimum concentration of herbicide Glufosinate-ammonium that inhibits the growth of the soybean plants in greenhouse condition. The soybean plants were tried with different concentrations of herbicide (5; 10; 1 5; 20; 25; 30 mg L-1 and a control without herbicide. The increase of the concentrations increased the necrosis of the plants and the use of 20 mgL-1 Glufosinato de amonio herbicide was sufficient to inhibit the plant growth. These results allow using this method of selection in programs of genetic improvement and selection of transgenic soybean plants

  6. Field Dissipation and Storage Stability of Glufosinate Ammonium and Its Metabolites in Soil

    OpenAIRE

    Zhang, Yun; Wang, Kai; Wu, Junxue; Zhang, Hongyan

    2014-01-01

    A simple analytical method was developed to measure concentrations of glufosinate ammonium and its metabolites, 3-methylphosphinico-propionic acid (MPP) and 2-methylphosphinico-acetic acid (MPA), in field soil samples. To determine the minimum quantification limit, samples were spiked at different levels (0.1, 0.5, and 1.0 mg/kg). Soil samples were extracted with ammonium hydroxide solution 5% (v/v), concentrated, and reacted with trimethyl orthoacetate (TMOA) in the presence of acetic acid f...

  7. Glufosinate ammonium clean-up procedure from water samples using SPE

    Science.gov (United States)

    Tayeb M., A.; Ismail B., S.; Mardiana-Jansar, K.; Ta, Goh Choo; Agustar, Hani Kartini

    2015-09-01

    For the determination of glufosinate ammonium residue in soil and water samples, different solid phase extraction (SPE) sorbent efficiency was studied. Four different SPE sorbents i.e.: CROMABOND PS-H+, CROMABOND PS-OH-, ISOLUTE ENV+, Water Sep-Pak and OASIS HLB were used. Sample clean-up performance was evaluated using high performance liquid chromatography (Agilent 1220 infinity LC) with fluorescence detector. Detection of FMO-derivatives was done at λ ex = 260 nm and λ em= 310 nm. OASIS HLB column was the most suitable for the clean-up in view of the overall feasibility of the analysis.

  8. Integrated Palmer Amaranth Management in Glufosinate-Resistant Cotton: II. Primary, Secondary and Conservation Tillage

    Directory of Open Access Journals (Sweden)

    Michael G. Patterson

    2013-01-01

    Full Text Available A three year field experiment was conducted to evaluate the role of soil inversion, cover crops and spring tillage methods for Palmer amaranth between-row (BR and within-row (WR management in glufosinate-resistant cotton. Main plots were two soil inversion treatments: fall inversion tillage (IT and non-inversion tillage (NIT. Subplots were three cover treatments: crimson clover, cereal rye or none (i.e., winter fallow; and the sub subplots were four secondary spring tillage methods: disking followed by (fb cultivator (DCU, disking fb chisel plow (DCH, disking fb disking (DD and no tillage (NT. Averaged over years and soil inversion, the crimson clover produced maximum cover biomass (4390 kg ha−1 fb cereal rye (3698 kg ha−1 and winter fallow (777 kg ha−1. Two weeks after planting (WAP and before the postemergence (POST application, Palmer amaranth WR and BR density were two- and four-times less, respectively, in IT than NIT. Further, Palmer amaranth WR and BR density were reduced two-fold following crimson clover and cereal rye than following winter fallow at 2 WAP. Without IT, early season Palmer amaranth densities were 40% less following DCU, DCH and DD, when compared with IT. Following IT, no spring tillage method improved Palmer amaranth control. The timely application of glufosinate + S-metolachlor POST tank mixture greatly improved Palmer amaranth control in both IT and NIT systems. The highest cotton yields were obtained with DD following cereal rye (2251 kg ha−1, DD following crimson clover (2213 kg ha−1 and DD following winter fallow (2153 kg ha−1. On average, IT cotton yields (2133 kg ha−1 were 21% higher than NIT (1766 kg ha−1. Therefore, from an integrated weed management standpoint, an occasional fall IT could greatly reduce Palmer amaranth emergence on farms highly infested with glyphosate-resistant Palmer amaranth. In addition, a cereal rye or crimson clover cover crop can effectively reduce early season Palmer

  9. A case of transient diabetes insipidus associated with poisoning by a herbicide containing glufosinate.

    Science.gov (United States)

    Takahashi, H; Toya, T; Matsumiya, N; Koyama, K

    2000-01-01

    The herbicide BASTA (AgrEvo, Germany), containing glufosinate ammonium (20%) and an anionic surfactant, polyoxyethylene alkylether sulfate (33%), is widely used. In acute oral BASTA poisoning, patients develop a variety of clinical signs, including disturbed consciousness, convulsions, and apnea. These effects are suspected to be due to the effects of glufosinate on the central nervous system. A 60-year-old man ingested 500 mL of BASTA herbicide in a suicide attempt. He developed not only unconsciousness, respiratory distress, and convulsions but also an increase in urine output (7885 mL/d), elevated serum sodium (167 mEq/L), elevated plasma osmolality (332 mOsm/kg), and a decrease in both urine osmolality (200 mOsm/kg) and urine specific gravity (1.003), which suggested the development of diabetes insipidus. The plasma level of antidiuretic hormone remained within the normal range (1.3 pg/mL), despite high plasma osmolality. The administration of desmopressin was successful in normalizing urine volume, specific gravity, and osmolality. Serum sodium corrected gradually within 48 hours. The possible mechanisms causing the diabetes insipidus are discussed.

  10. Toxicity of the herbicide glufosinate-ammonium to predatory insects and mites of Tetranychus urticae (Acari: Tetranychidae) under laboratory conditions.

    Science.gov (United States)

    Ahn, Y J; Kim, Y J; Yoo, J K

    2001-02-01

    The toxicities of the herbicide glufosinate-ammonium to three predatory insect and two predatory mite species of Tetranychus urticae Koch were determined in the laboratory by the direct contact application. At a concentration of 540 ppm (a field application rate for weed control in apple orchards), glufosinate-ammonium was almost nontoxic to eggs of Amblyseius womersleyi Schicha, Phytoseiulus persimilis Athias-Henriot, and T. urticae but highly toxic to nymphs and adults of these three mite species, indicating that a common mode of action between predatory and phytophagous mites might be involved. In tests with predatory insects using 540 ppm, glufosinate-ammonium revealed little or no harm to larvae and pupae of Chrysopa pallens Rambur but was slightly harmful to eggs (71.2% mortality), nymphs (65.0% mortality), and adults (57.7% mortality) of Orius strigicollis Poppius. The herbicide showed no direct effect on eggs and adults of Harmonia axyridis (Pallas) but was harmful, slightly harmful, and harmless to first instars (100% mortality), fourth instars (51.1% mortality), and pupae (24.5% mortality), respectively. The larvae and nymphs of predators died within 12 h after treatment, suggesting that the larvicidal and nymphicidal action may be attributable to a direct effect rather than an inhibitory action of chitin synthesis. On the basis of our data, glufosinate-ammonium caused smaller effects on test predators than on T. urticae with the exception of P. persimilis, although the mechanism or cause of selectivity remains unknown. Glufosinate-ammonium merits further study as a key component of integrated pest management.

  11. Reducing the 2, 4 D+MCPA Antagonism from Hard Spray Waters by Ammonium Sulfate

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    Seyed Hossein Torabi

    2017-03-01

    Full Text Available Introduction: Water is the main carrier of herbicides (HC that its quality plays an important role in herbicide performance hard water has a high concentration of Ca++ and Mg++ and reviews have shown that calcium, manganese and zinc are the main factors reducing the effectiveness of weak acid herbicides. Weak acid herbicides such as glyphosate, paraquat, clethodim and 2, 4 D are compounds that release the H+ ions once dissolved in water, but just slightly. Therefore, herbicides that are weak acids partially dissociate. Herbicides not dissociated (the compound remains whole are more readily absorbed by plant foliage than those that dissociate. Dissociated herbicide molecules have a negative charge. After being dissociated, herbicides might remain as negatively charged molecules, or they might bind with other positively charged cations. Binding to some cations improves herbicide uptake and absorption, binding to others such as Ca++ and Mg++ antagonizes herbicide activity by decreasing absorption or activity in the cell. To correct such carriers, the use of adjuvants, such as ammonium sulphate (AMS, is recommended, which can reduce the use of herbicides and cause economic savings. The aim of this study was to investigate the simple effects and interactions between different amounts of AMS and carrier hardness (CH levels on 2, 4 D + MCPA herbicide efficacy in controlling white clover (Trifolium repens L. in turf grass. Materials and Methods: The experiment was laid out in a RCBD with three replications for each treatment during spring-summer 2013 in 10 years old mixed cold season turf grass (Festuca rubra + Poa pratensis + Poa pratensis dominated by white clover in Mashhad (Iran. The treatments were the factorial combination of four carrier hardness (CH rates (Deionized, 45, 90 and 180 ppm of Ca++ +Mg++ and three Ammonium Sulfate (AMS rates (0, 2, 3 and 4 Kg per100 L of carrier water were studied. The turf was sprayed with 2, 4 D + MCPA (67.5% SL at

  12. The effect of high concentrations of glufosinate ammonium on the yield components of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the bar gene.

    Science.gov (United States)

    Áy, Zoltán; Mihály, Róbert; Cserháti, Mátyás; Kótai, Éva; Pauk, János

    2012-01-01

    We present an experiment done on a bar(+) wheat line treated with 14 different concentrations of glufosinate ammonium-an effective component of nonselective herbicides-during seed germination in a closed experimental system. Yield components as number of spikes per plant, number of grains per spike, thousand kernel weight, and yield per plant were thoroughly analysed and statistically evaluated after harvesting. We found that a concentration of glufosinate ammonium 5000 times the lethal dose was not enough to inhibit the germination of transgenic plants expressing the bar gene. Extremely high concentrations of glufosinate ammonium caused a bushy phenotype, significantly lower numbers of grains per spike, and thousand kernel weights. Concerning the productivity, we observed that concentrations of glufosinate ammonium 64 times the lethal dose did not lead to yield depression. Our results draw attention to the possibilities implied in the transgenic approaches.

  13. The Effect of High Concentrations of Glufosinate Ammonium on the Yield Components of Transgenic Spring Wheat (Triticum aestivum L. Constitutively Expressing the bar Gene

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    Zoltán Áy

    2012-01-01

    Full Text Available We present an experiment done on a bar+ wheat line treated with 14 different concentrations of glufosinate ammonium—an effective component of nonselective herbicides—during seed germination in a closed experimental system. Yield components as number of spikes per plant, number of grains per spike, thousand kernel weight, and yield per plant were thoroughly analysed and statistically evaluated after harvesting. We found that a concentration of glufosinate ammonium 5000 times the lethal dose was not enough to inhibit the germination of transgenic plants expressing the bar gene. Extremely high concentrations of glufosinate ammonium caused a bushy phenotype, significantly lower numbers of grains per spike, and thousand kernel weights. Concerning the productivity, we observed that concentrations of glufosinate ammonium 64 times the lethal dose did not lead to yield depression. Our results draw attention to the possibilities implied in the transgenic approaches.

  14. The Effect of High Concentrations of Glufosinate Ammonium on the Yield Components of Transgenic Spring Wheat (Triticum aestivum L.) Constitutively Expressing the bar Gene

    OpenAIRE

    Áy, Zoltán; Mihály, Róbert; Cserháti, Mátyás; Kótai, Éva; Pauk, János

    2012-01-01

    We present an experiment done on a bar + wheat line treated with 14 different concentrations of glufosinate ammonium—an effective component of nonselective herbicides—during seed germination in a closed experimental system. Yield components as number of spikes per plant, number of grains per spike, thousand kernel weight, and yield per plant were thoroughly analysed and statistically evaluated after harvesting. We found that a concentration of glufosinate ammonium 5000 times the lethal dose w...

  15. Transgene Flow from Glufosinate-Resistant Rice to Improved and Weedy Rice in China

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    Yong-liang LU

    2014-09-01

    Full Text Available The development of transgenic rice with novel traits in China can increase rice productivity, but transgene flow to improved or weedy rice has become a major concern. We aimed to evaluate the potential maximum frequencies of transgene flow from glufosinate-resistant rice to improved rice cultivars and weedy rice. Treatments were arranged in randomized complete blocks with three replicates. Experiments were conducted between 2009 and 2010 at the Center for Environmental Safety Supervision and Inspection for Genetically Modified Plants, China National Rice Research Institute, Hangzhou, China. Glufosinate-resistant japonica rice 99-1 was the pollen donor. The pollen recipients were two inbred japonica rice (Chunjiang 016 and Xiushui 09, two inbred indica rice (Zhongzu 14 and Zhongzao 22, two indica hybrid rice (Zhongzheyou 1 and Guodao 1, and one weedy indica rice (Taizhou weedy rice. The offspring of recipients were planted in the field and sprayed with a commercial dose of glufosinate. Leaf tissues of survivors were analyzed by polymerase chain reaction to detect the presence of the transgene. The frequency of gene flow ranged from 0 to 0.488%. In 2009, the order of gene flow frequency was as follows: weedy rice > Chunjiang 016 > Xiushui 09 and Zhongzu 14 > Guodao 1, Zhongzheyou 1 and Zhongzao 22. Gene flow frequencies were generally higher in 2009 than in 2010, but did not differ significantly among rice materials. Gene flow frequency was the highest in weedy rice followed by the inbred japonica rice. The risk of gene flow differed significantly between years and year-to-year variance could mask risk differences among pollen recipients. Gene flow was generally lesser in taller pollen recipients than in shorter ones, but plant height only accounted for about 30% of variation in gene flow. When flowering synchrony was maximized, as in this study, low frequencies of gene flow occurred from herbicide-resistant japonica rice to other cultivars and

  16. Antagonism of acetylcholine by adrenaline antagonists

    Science.gov (United States)

    Benfey, B. G.; Grillo, S. A.

    1963-01-01

    Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guinea-pig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pA10 of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose-ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea-pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pA10 (60 min of contact) was 6.6. The pA10 of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2-diethylaminomethylbenzo-1,4-dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine. PMID:13967429

  17. Sensitivity of Phaseolus vulgaris cv. `CIAP 7247F' plants to Glufosinate ammonium herbicide in greenhouse

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    Idalmis Bermúdez-Caraballoso

    2014-01-01

    Full Text Available Genetic breeding in Phaseolus by genetic transformation requires an efficient selection system. The present investigation was aimed to determine the minimum lethal concentration of glufosinate-ammonium (Finale ® in beans plants cv. `CIAP 7247F' grown in greenhouse. Different concentrations of the herbicide were applied to the foliage of plants in acclimatization phase (20, 30 y 40 mg l-1 and the control. Results showed that the minimum lethal concentration in plants in acclimatization phase was 30 mg l-1. Results also demonstrated that is possible the use of the herbicide as a selective agent of beans transformants cv. `CIAP 7247F' carrying the bar gene. Keywords: genetic transformation, herbicide, selective agent, tissue culture

  18. Ação dos herbicidas atrazine e glufosinate de amônio no aproveitamento de nitrogênio pelas plantas de milho Herbicides atrazine and ammonium glufosinate action on nitrogen usage by corn plants

    OpenAIRE

    N.G. Fleck; M.A. Rizzardi; R. Neves; D. Agostinetto

    2001-01-01

    A absorção vegetal do nitrogênio (N) presente no solo ou fornecido via fertilização é regulada por um complexo enzimático que age de forma conjunta e ordenada na planta. O objetivo desta pesquisa foi investigar efeitos dos herbicidas atrazine e glufosinate de amônio na absorção do N pelas plantas e os efeitos que exercem em características de plantas de milho. Em um dos experimentos (experimento 1) foram testadas três doses de atrazine (0, 200 e 2.000 g i.a. ha-1) e de glufosinate de amônio (...

  19. Ação dos herbicidas atrazine e glufosinate de amônio no aproveitamento de nitrogênio pelas plantas de milho Herbicides atrazine and ammonium glufosinate action on nitrogen usage by corn plants

    Directory of Open Access Journals (Sweden)

    N.G. Fleck

    2001-08-01

    Full Text Available A absorção vegetal do nitrogênio (N presente no solo ou fornecido via fertilização é regulada por um complexo enzimático que age de forma conjunta e ordenada na planta. O objetivo desta pesquisa foi investigar efeitos dos herbicidas atrazine e glufosinate de amônio na absorção do N pelas plantas e os efeitos que exercem em características de plantas de milho. Em um dos experimentos (experimento 1 foram testadas três doses de atrazine (0, 200 e 2.000 g i.a. ha-1 e de glufosinate de amônio (0; 40 e 80 g i.a. ha-1 e duas doses de N (0 e 90 kg ha-1. No segundo experimento (experimento 2 foram testados três tratamentos herbicidas (atrazine, 200 g i.a. ha-1; glufosinate de amônio, 40 g i.a. ha-1; atrazine + glufosinate de amônio, 200 + 40 g i.a. ha-1; e testemunha, duas fontes de N (uréia e nitrato de amônio e duas doses de N (0 e 100 kg ha-1. Os efeitos dos tratamentos foram avaliados aos 10 e 20 dias após a aplicação (DAA dos herbicidas, no experimento 1, e quando as plantas de milho apresentavam 10 folhas desenvolvidas (15 DAA e no pendoamento do milho (40 DAA, no experimento 2. A partir da análise dos resultados obtidos, constatou-se que aplicação de N em cobertura na cultura do milho promove aumento na maioria dos componentes do rendimento e incrementa em 35% o rendimento de grãos e que esse efeito ocorre de forma independente da fonte de N utilizada: uréia ou nitrato de amônio. Não ocorre interação entre os fatores relacionados aos herbicidas inibidores do fotossistema II (atrazine e da síntese de glutamina (glufosinate de amônio e aplicação de N em cobertura no milho. O uso destes herbicidas em doses reduzidas (abaixo da recomendada, aplicados isoladamente ou combinados, não afetou o rendimento de grãos nem os componentes do rendimento da cultura do milho. O herbicida atrazine tem pequena influência nos teores de clorofila e de N em milho, mas, em algumas situações, sua ação é favorável, especialmente

  20. Fate of the herbicides glyphosate, glufosinate-ammonium, phenmedipham, ethofumesate and metamitron in two Finnish arable soils.

    Science.gov (United States)

    Laitinen, Pirkko; Siimes, Katri; Eronen, Liisa; Rämö, Sari; Welling, Leena; Oinonen, Seija; Mattsoff, Leona; Ruohonen-Lehto, Marja

    2006-06-01

    The fate of five herbicides (glyphosate, glufosinate-ammonium, phenmedipham, ethofumesate and metamitron) was studied in two Finnish sugar beet fields for 26 months. Soil types were sandy loam and clay. Two different herbicide-tolerant sugar beet cultivars and three different herbicide application schedules were used. Meteorological data were collected throughout the study and soil properties were thoroughly analysed. An extensive data set of herbicide residue concentrations in soil was collected. Five different soil depths were sampled. The study was carried out using common Finnish agricultural practices and represents typical sugar beet cultivation conditions in Finland. The overall observed order of persistence was ethofumesate > glyphosate > phenmedipham > metamitron > glufosinate-ammonium. Only ethofumesate and glyphosate persisted until the subsequent spring. Seasonal variation in herbicide dissipation was very high and dissipation ceased almost completely during winter. During the 2 year experiment no indication of potential groundwater pollution risk was obtained, but herbicides may cause surface water pollution. Copyright (c) 2006 Society of Chemical Industry

  1. Takotsubo cardiomyopathy as a delayed complication with a herbicide containing glufosinate ammonium in a suicide attempt: a case report.

    Science.gov (United States)

    Tominaga, Keiichiro; Izumi, Manabu; Suzukawa, Masayuki; Shinjo, Takafumi; Izawa, Yoshimitsu; Yonekawa, Chikara; Ano, Masaki; Yamashita, Keisuke; Muronoi, Tomohiro; Mochiduki, Reiko

    2012-01-01

    Background. Glufosinate ammonium has a famous delayed complication as respiratory failure, however, delayed cardiogenic complication is not well known. Objectives. The aim of this study is to report a takotsubo cardiomyopathy as a delayed complication of glufosinate ammonium for suicide attempt. Case Report. A 75-year-old woman ingested about 90 mL of Basta, herbicide for suicide attempt at arousal during sleep. She came to our hospital at twelve hours after ingesting. She was admitted to our hospital for fear of delayed respiratory failure. Actually, she felt down to respiratory failure, needing a ventilator with intubation at 20 hours after ingesting. Procedure around respiratory management had smoothly done with no delay. Her vital status had been stable, however, she felt down to circulatory failure and diagnosed as Takotsubo cardiomyopathy at about 41 hours after ingestion. There was no trigger activities or events to evoke mental and physical stresses. Conclusion. We could successfully manage takotsubo cardiomyopathy resulted in circulatory failure in a patient with glufosinate poisoning for suicide attempt. Takotsubo cardiomyopathy should be taken into consideration if circulatory failure is observed for unexplained reasons.

  2. Takotsubo Cardiomyopathy as a Delayed Complication with a Herbicide Containing Glufosinate Ammonium in a Suicide Attempt: A Case Report

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    Keiichiro Tominaga

    2012-01-01

    Full Text Available Background. Glufosinate ammonium has a famous delayed complication as respiratory failure, however, delayed cardiogenic complication is not well known. Objectives. The aim of this study is to report a takotsubo cardiomyopathy as a delayed complication of glufosinate ammonium for suicide attempt. Case Report. A 75-year-old woman ingested about 90 mL of Basta, herbicide for suicide attempt at arousal during sleep. She came to our hospital at twelve hours after ingesting. She was admitted to our hospital for fear of delayed respiratory failure. Actually, she felt down to respiratory failure, needing a ventilator with intubation at 20 hours after ingesting. Procedure around respiratory management had smoothly done with no delay. Her vital status had been stable, however, she felt down to circulatory failure and diagnosed as Takotsubo cardiomyopathy at about 41 hours after ingestion. There was no trigger activities or events to evoke mental and physical stresses. Conclusion. We could successfully manage takotsubo cardiomyopathy resulted in circulatory failure in a patient with glufosinate poisoning for suicide attempt. Takotsubo cardiomyopathy should be taken into consideration if circulatory failure is observed for unexplained reasons.

  3. The Antagonism Mechanism Of Trichoderma spp. Towards Fusarium solani Mold

    OpenAIRE

    Utami Sri Hastuti; Indriana Rahmawati

    2016-01-01

    The antagonism ability of seven Trichoderma isolates towards F.solani have been observed and tested by dual culture technique. The antagonism mechanism observed by microscopic observation with light microscope and Scanning Electron Microscopy (SEM). The research result showed seven species of Trichoderma molds have different antagonism ability towards F.solani each other. The antagonism mechanism observed by light microscope and Scanning Electron Microscopy were mycoparasitism, antibiosis, an...

  4. The Antagonism Mechanism Of Trichoderma spp. Towards Fusarium solani Mold

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    Utami Sri Hastuti

    2016-09-01

    Full Text Available The antagonism ability of seven Trichoderma isolates towards F.solani have been observed and tested by dual culture technique. The antagonism mechanism observed by microscopic observation with light microscope and Scanning Electron Microscopy (SEM. The research result showed seven species of Trichoderma molds have different antagonism ability towards F.solani each other. The antagonism mechanism observed by light microscope and Scanning Electron Microscopy were mycoparasitism, antibiosis, and competition.

  5. Hyperammonemia following glufosinate-containing herbicide poisoning: a potential marker of severe neurotoxicity.

    Science.gov (United States)

    Mao, Yan-Chiao; Wang, Jiaan-Der; Hung, Dong-Zong; Deng, Jou-Fang; Yang, Chen-Chang

    2011-01-01

    Glufosinate-ammonium (GLA) is the active ingredient of certain widely used non-selective contact herbicides ("e.g.," Basta). Although it is thought to be much less toxic to humans than to plants, deliberate ingestion of GLA could still lead to serious effects ("e.g.," neurotoxicity) or even death. Three cases presented with delayed-onset neurotoxicity including stupor, delirium, seizures, coma, and amnesia after ingesting large amount of Basta. Considering that GLA could irreversibly inhibit glutamine synthetase (GS) in plants, we performed serial measurements of serum ammonia in those patients and revealed marked hyperammonemia in all of them. All patients recovered with the sequelae of persistent amnesia after receiving intensive care and hemodialysis. We speculated that the occurrence of hyperammonemia might at least be partially related to GS inhibition in humans. Moreover, hyperammonemia could serve as a potential marker of severe neurotoxicity, especially prolonged amnesia, following massive ingestion of GLA-containing herbicides. The possible dose-response relation between GLA exposure and serum ammonia level, however, needs more investigations.

  6. Pre- and postnatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

    Science.gov (United States)

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

  7. Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization.

    Science.gov (United States)

    Herzine, Ameziane; Laugeray, Anthony; Feat, Justyne; Menuet, Arnaud; Quesniaux, Valérie; Richard, Olivier; Pichon, Jacques; Montécot-Dubourg, Céline; Perche, Olivier; Mortaud, Stéphane

    2016-01-01

    Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

  8. Resistance to Phosphinothricin (Glufosinate) and Its Utilization as a Nitrogen Source by Chlamydomonas reinhardtii.

    Science.gov (United States)

    Franco, A R; Lopez-Siles, F J; Cardenas, J

    1996-10-01

    Wild-type strain 21gr of the green alga Chlamydomonas reinhardtii was resistant to the ammonium salt of l-phosphinothricin (PPT, also called glufosinate), an irreversible inhibitor of glutamine synthetase activity and the main active component of the herbicide BASTA (AgrEvo, Frankfurt am Main, Germany). Under the same conditions, however, this strain was highly sensitive to l-methionine-S-sulfoximine, a structural analog of PPT which has been reported to be 5 to 10 times less effective than PPT as an inhibitor in plants. Moreover, this alga was able to grow with PPT as the sole nitrogen source when this compound was provided at low concentrations. This utilization of PPT was dependent upon the addition of acetate and light and did not take place in the presence of ammonium. Resistance was due neither to the presence of N-acetyltransferase or transaminase activity nor to the presence of glutamine synthetase isoforms resistant to PPT. By using l-[methyl-(sup14)C]PPT, we demonstrated that resistance is due to lack of PPT transport into the cells. This strongly suggests that PPT and l-methionine-S-sulfoximine enter the cells through different systems. Growth with PPT is supported by its deamination by an l-amino acid oxidase activity which has been previously described to be located at the periplasm.

  9. Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

    Science.gov (United States)

    Calas, André-Guilhem; Perche, Olivier; Richard, Olivier; Perche, Astrid; Pâris, Arnaud; Lauga, Fabien; Herzine, Ameziane; Palomo, Jennifer; Ardourel, Marie-Yvonne; Menuet, Arnaud; Mortaud, Stéphane; Pichon, Jacques; Montécot-Dubourg, Céline

    2016-05-04

    Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.

  10. Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

    Science.gov (United States)

    Maillet, Isabelle; Perche, Olivier; Pâris, Arnaud; Richard, Olivier; Gombault, Aurélie; Herzine, Ameziane; Pichon, Jacques; Huaux, Francois; Mortaud, Stéphane; Ryffel, Bernhard; Quesniaux, Valérie F J; Montécot-Dubourg, Céline

    2016-11-01

    Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  11. Cholinesterase activities and behavioral changes in Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed to glufosinate ammonium herbicide.

    Science.gov (United States)

    Peltzer, Paola M; Junges, Celina M; Attademo, Andrés M; Bassó, Agustín; Grenón, Paula; Lajmanovich, Rafael C

    2013-09-01

    In this study, amphibian tadpoles of Hypsiboas pulchellus were exposed to herbicide Liberty®, which contains glufosinate ammonium (GLA), for 48 h to the following concentrations: 0 (control), 3.55, 4.74, 6.32, 8.43, 11.25, 15, 20, 26.6, and 35.5 mg GLA L(-1). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, as well as swimming capabilities (swimming speed and mean distance) were measured in tadpoles whose concentrations displayed survival rates > 85 %. Our results reveal that sublethal concentrations of GLA significantly inhibited both AChE and BChE activities in tadpoles with respect to the control, showing a concentration-dependent inhibitory effect. The highest inhibition percentages of AChE (50.86%) and BChE (53.02%) were registered in tadpoles exposed to 15 mg GLA L(-1). At this concentration, a significant increase of the swimming speed and mean distance were found in exposed tadpoles with respect to the control, as well as a negative and significant correlation between swimming speed and BChE activity, thus suggesting that this enzyme inhibition is related to an increase in swimming speed. Therefore, exposure of tadpoles to GLA in the wild at concentrations similar to those tested here may have adverse consequences at population level because neurotransmission and swimming performance are essential for tadpole performance and survival.

  12. Glufosinate-ammonium reduces growth and aflatoxin B1 production by Aspergillus flavus.

    Science.gov (United States)

    Tubajikat, K M; Damann, K E

    2002-09-01

    The herbicide glufosinate-ammonium (GA) [butanoic acid, 2-amino-4-(hydroxymethylphosphinyl)-ammonium salt] was tested at concentrations from 2 to 2,000 g GA per ml for activity against growth and aflatoxin B1 (AFB) production by the mycotoxigenic fungus Aspergillus flavus Link:Fr. The highest concentration (2,000 microg GA per ml) reduced colony diameter of A. flavus strain AF13 by 80%. AFB1 production was inhibited by 90% at this concentration. Reduction in mycelial dry weight and AFB1 production in response to GA application ranged from 17.2 to 97.1% and from 39.1 to 90.1%, respectively. Of four concentrations tested, 2 microg GA per ml was weakly inhibitory. In the kernel screening assay, AFB1 production was inhibited 60 to 91% when kernels were preimmersed or immersed 5 days after incubation in 200 microg GA per ml. Both concentrations (2 and 200 microg GA per ml) reduced seed germination by 25 to 50%. Results indicate that GA has an inhibitory effect on growth and AFB1 production by A. flavus.

  13. Protein binding of glufosinate and factors affecting it revealed by an equilibrium dialysis technique.

    Science.gov (United States)

    Hori, Y; Koyama, K; Fujisawa, M; Nakajima, M; Shimada, K; Hirose, Y; Kohda, Y; Akuzawa, H

    2001-09-01

    We investigated the protein binding of glufosinate ammonium (GLF) and several factors affecting this binding using human serum albumin (HSA) and human volunteer serum under various conditions. The mean ratios of the free GLF (RFr-GLF) to 4% HSA were examined in the sera of patients described elsewhere at GLF levels from 1 microg/mL to 500 microg/mL; the range was found to be only from 0.80 to 0.88. Neither the incubation temperature nor buffers containing different chloride ion concentrations had any effect on the RFr-GLF to HSA. Moreover, the addition of heparin, glycoprotein-alpha1-acid (AAG), and sodium azide had no effect on the RFr-GLF. However, pH of the isotonic phosphate buffer and the addition of palmitic or oleic acid were seen to have an effect. In this study, the mean RFr-GLF to healthy human serum was 0.99. This high value was evidenced that GLF was rapidly excreted through the renal route.

  14. Perinatal exposure to glufosinate ammonium herbicide impairs neurogenesis and neuroblast migration through cytoskeleton destabilization

    Directory of Open Access Journals (Sweden)

    Ameziane Herzine

    2016-08-01

    Full Text Available Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ. During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA, leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray, Herzine et al. 2014 . Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

  15. Perinatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

    Directory of Open Access Journals (Sweden)

    Anthony eLaugeray

    2014-11-01

    Full Text Available Glufosinate ammonium (GLA is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in normalized brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between perinatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

  16. Glyphosate and glufosinate detection at electrogenerated NiAl-LDH thin films

    Energy Technology Data Exchange (ETDEWEB)

    Khenifi, Aicha [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Laboratoire de physico-chimie des materiaux, catalyse et environnement Usto, Oran, El M' nouar (Algeria); Derriche, Zoubir [Laboratoire de physico-chimie des materiaux, catalyse et environnement Usto, Oran, El M' nouar (Algeria); Forano, Claude; Prevot, Vanessa [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Mousty, Christine, E-mail: Christine.Mousty@univ-bpclermont.fr [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Scavetta, Erika, E-mail: scavetta@fci.unibo.it [Laboratorio di Chimica Analitica, Dipartimento di Chimica Fisica ed Inorganica, Universita degli Studi di Bologna (Italy); Ballarin, Barbara; Guadagnini, Lorella; Tonelli, Domenica [Laboratorio di Chimica Analitica, Dipartimento di Chimica Fisica ed Inorganica, Universita degli Studi di Bologna (Italy)

    2009-11-10

    An amperometric sensor based on Ni{sub 1-x}Al{sub x}(OH){sub 2}NO{sub 3x}.nH{sub 2}O layered double hydroxide (LDH) has been developed for the electrochemical analysis in one step of two herbicides: glyphosate (N-(phosphonomethyl)glycine, Glyp) and glufosinate ((DL-homoalanine-4-yl)-methylphosphinic acid, Gluf). NiAl-LDH was prepared by coprecipitation or by electrodeposition at the Pt electrode surface. Inorganic films were fully characterized by X-ray diffraction, Raman spectroscopy and scanning electron microscopy. Adsorption isotherms of Glyp onto this inorganic lamellar material have been established. Electrocatalytic oxidation of Glyp and Gluf is possible at the Ni{sup 3+} centres of the structure. The electrochemical responses of the NiAl-LDH modified electrode were obtained by cyclic voltammetry and chronoamperometry at 0.49 V/SCE as a function of herbicide concentration in 0.1 M NaOH solution. The electrocatalytic response showed a linear dependence on the Glyp concentration ranging between 0.01 and 0.9 mM with a detection limit of 1 {mu}M and sensitivity 287 mA/M cm{sup 2}. The sensitivity found for Gluf was lower (178 mA/M cm{sup 2}).

  17. Herbicide glufosinate inhibits yeast growth and extends longevity during wine fermentation.

    Science.gov (United States)

    Vallejo, Beatriz; Picazo, Cecilia; Orozco, Helena; Matallana, Emilia; Aranda, Agustín

    2017-09-29

    Glufosinate ammonium (GA) is a widely used herbicide that inhibits glutamine synthetase. This inhibition leads to internal amino acid starvation which, in turn, causes the activation of different nutrient sensing pathways. GA also inhibits the enzyme of the yeast Saccharomyces cerevisiae in such a way that, although it is not used as a fungicide, it may alter yeast performance in industrial processes like winemaking. We describe herein how GA indeed inhibits the yeast growth of a wine strain during the fermentation of grape juice. In turn, GA extends longevity in a variety of growth media. The biochemical analysis indicates that GA partially inhibits the nutrient sensing TORC1 pathway, which may explain these phenotypes. The GCN2 kinase mutant is hypersensitive to GA. Hence the control of translation and amino acid biosynthesis is required to also deal with the damaging effects of this pesticide. A global metabolomics analysis under winemaking conditions indicated that an increase in amino acid and in polyamines occurred. In conclusion, GA affects many different biochemical processes during winemaking, which provides us with some insights into both the effect of this herbicide on yeast physiology and into the relevance of the metabolic step for connecting nitrogen and carbon metabolism.

  18. Metodologia para determinação de efeitos fisiológicos e metabólicos do glufosinate em soja

    OpenAIRE

    Barberis, Luis Rodrigo Miyamoto [UNESP

    2012-01-01

    O glufosinate é derivado do fosfinotricina, uma toxina microbiana natural isolada a partir de duas espécies de fungos Streptomyces. Atua inibindo a atividade da enzima glutamina sintetase, que é necessária para a produção do aminoácido glutamina e para a desintoxicação da amônia pela planta. Objetivou-se neste trabalho avaliar a intoxicação e alterações fisiológicas e bioquímicas causadas pelo glufosinate em plantas de soja. O experimento foi conduzido em casa-de-vegetação, no Núcleo de Pesqu...

  19. Glufosinate herbicide-tolerant (LibertyLink) rice vs. conventional rice in diets for growing-finishing swine.

    Science.gov (United States)

    Cromwell, G L; Henry, B J; Scott, A L; Gerngross, M F; Dusek, D L; Fletcher, D W

    2005-05-01

    Genetically modified (GM) rice (LibertyLink, event LLRICE62) that is tolerant to glufosinate ammonium (Liberty) herbicide was compared with a near-isogenic (NI) conventional medium-grain brown rice (cultivar, Bengal) and a commercially milled long-grain brown rice in diets for growing-finishing pigs. The GM and NI rice were grown in 2000. The GM rice was from fields treated (GM+) or not treated (GM-) with glufosinate herbicide. The GM- and NI rice were grown using herbicide regimens typical of southern United States rice production practices. The four rice grains were similar in composition. Growing-finishing pigs (n = 96) were fed fortified rice-soybean meal diets containing the four different rice grains from 25 to 106 kg BW. Diets contained 0.99% lysine initially (growing phase), with lysine decreased to 0.80% (early finishing phase) and 0.65% (late finishing phase), when pigs reached 51 and 77 kg, respectively. The percentage of rice in the four diets was constant during each of the three phases (72.8, 80.0, and 85.8% for the growing, early-finishing, and late-finishing phases, respectively). There were six pen replicates (three pens of barrows and three pens of gilts) and four pigs per pen for each dietary treatment. All pigs were slaughtered at the termination of the study to collect carcass data. At the end of the 98-d experiment, BW gain, feed intake (as-fed basis), and feed:gain ratio did not differ (P > 0.05) for pigs fed the GM+ vs. conventional rice diets, but growth performance traits of pigs fed the GM+ rice diets were superior (P glufosinate herbicide-tolerant rice was similar in composition and nutritional value to conventional rice for growing-finishing pigs.

  20. Reconceptualizing synergism and antagonism among multiple stressors

    OpenAIRE

    Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

    2015-01-01

    The potential for complex synergistic or antagonistic interactions between multiple stressors presents one of the largest uncertainties when predicting ecological change but, despite common use of the terms in the scientific literature, a consensus on their operational definition is still lacking. The identification of synergism or antagonism is generally straightforward when stressors operate in the same direction, but if individual stressor effects oppose each other, the definition of syner...

  1. Triclosan antagonizes fluconazole activity against Candida albicans.

    LENUS (Irish Health Repository)

    Higgins, J

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg\\/L. However, at subinhibitory concentrations (0.5-2 mg\\/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.

  2. Intoxicação e alterações metabólicas do algodão sensível e resistente ao amônio glufosinate

    OpenAIRE

    Latorre, Débora de Oliveira [UNESP

    2014-01-01

    The Liberty Link cotton cultivars are those that resist a dose of ammonium glufosinate application that normally would be recommended for other biotypes species .These cotton plants are constitute genetically with gene that encodes the production of enzyme phosphinothricin acetyl transferase (PAT) responsible for the acetylation of glufosinate ammonium, inactivating it in the plant. The cotton cultivar FiberMax® 975 WideStrike has present in i ts DNA the gene PAT and present intermediate meta...

  3. Natural Protection of Wood with Antagonism Fungi

    Directory of Open Access Journals (Sweden)

    Alba ZAREMSKI

    2011-03-01

    Full Text Available Biological environments contain a certain number of microbial populations which, within a givenecological niche, display various relations ranging from symbiosis to parasitism. Researchers have beeninterested in these types of relations for around fifty years, especially in one very particular type ofrelationship: the antagonism exerted between individuals of the same microbial population.Today, the role played by biological agents, bringing into play inhibitive or destructive antibioticsubstances, reveals a certain potential for their use in controlling microorganisms associated with suchdegradation processes.The work undertaken by HydroQuébec and CIRAD involved two types of experiment: 1 in Petri dishes toassess and characterize the antagonistic capacity of Trichoderma against white rot and brown rot fungi; 2on pieces taken from untreated poles in order to study confrontation between the basidiomycete and theantagonistic strain in wood.This study investigated the antagonism of three ascomycetes of the genus Trichoderma against two whiterot basidiomycetes, Pycnoporus sanguineus and Coriolus versicolor, and two brown rot basidiomycetes,Antrodia sp. and Coniophora puteana, through direct confrontation in Petri dishes and in the wood ofHydroQuébec poles.The results obtained seemed to complete each other coherently. They revealed that the Trichodermagroup of fungi was not aggressive to wood and the results obtained after direct confrontation in Petri disheswere confirmed in wood.By directly exposing the different basidiomycetes and antagonists to each other in Petri dishes, two bytwo, we effectively revealed an antagonism effect for a large majority of the pairs. However, there wassubstantial variability in reactions from one pair to the next.

  4. Reconceptualizing synergism and antagonism among multiple stressors.

    Science.gov (United States)

    Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

    2015-04-01

    The potential for complex synergistic or antagonistic interactions between multiple stressors presents one of the largest uncertainties when predicting ecological change but, despite common use of the terms in the scientific literature, a consensus on their operational definition is still lacking. The identification of synergism or antagonism is generally straightforward when stressors operate in the same direction, but if individual stressor effects oppose each other, the definition of synergism is paradoxical because what is synergistic to one stressor's effect direction is antagonistic to the others. In their highly cited meta-analysis, Crain et al. (Ecology Letters, 11, 2008: 1304) assumed in situations with opposing individual effects that synergy only occurs when the cumulative effect is more negative than the additive sum of the opposing individual effects. We argue against this and propose a new systematic classification based on an additive effects model that combines the magnitude and response direction of the cumulative effect and the interaction effect. A new class of "mitigating synergism" is identified, where cumulative effects are reversed and enhanced. We applied our directional classification to the dataset compiled by Crain et al. (Ecology Letters, 11, 2008: 1304) to determine the prevalence of synergistic, antagonistic, and additive interactions. Compared to their original analysis, we report differences in the representation of interaction classes by interaction type and we document examples of mitigating synergism, highlighting the importance of incorporating individual stressor effect directions in the determination of synergisms and antagonisms. This is particularly pertinent given a general bias in ecology toward investigating and reporting adverse multiple stressor effects (double negative). We emphasize the need for reconsideration by the ecological community of the interpretation of synergism and antagonism in situations where

  5. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M.; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric

    2010-01-01

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  6. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten

    2010-08-22

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  7. Forced Normalization: Antagonism Between Epilepsy and Psychosis.

    Science.gov (United States)

    Kawakami, Yasuhiko; Itoh, Yasuhiko

    2017-05-01

    The antagonism between epilepsy and psychosis has been discussed for a long time. Landolt coined the term "forced normalization" in the 1950s to describe psychotic episodes associated with the remission of seizures and disappearance of epileptiform activity on electroencephalograms in individuals with epilepsy. Since then, neurologists and psychiatrists have been intrigued by this phenomenon. However, although collaborative clinical studies and basic experimental researches have been performed, the mechanism of forced normalization remains unknown. In this review article, we present a historical overview of the concept of forced normalization, and discuss potential pathogenic mechanisms and clinical diagnosis. We also discuss the role of dopamine, which appears to be a key factor in the mechanism of forced normalization. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Agonism and antagonism at the insulin receptor

    DEFF Research Database (Denmark)

    Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia

    2012-01-01

    Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new...... insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been...... shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B'29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR...

  9. Determination of the minimal inhibitory concentration of Ammonium glufosinate in organogenic calli of Phaseolus vulgaris cv. `CIAP 7247F'

    OpenAIRE

    Idalmis Bermúdez-Caraballoso; Raúl Collado; Lourdes R. García; Novisel Veitía; Amanda Martirena; Damaris Torres; Carlos Romero; Gert Angenon

    2012-01-01

    An efficient selection system is necessary for distinguishing transformed cells of the untransformed tissue. This study aimed to determine the minimum inhibitory concentration of the herbicide Ammonium glufosinate in organogenic calli of Phaseolus vulgaris cv. CIAP 7247F, to use it as a selective agent in the process of genetic transformation. Fragments (4-5 mm) of proliferated calli after second subculture were used as explant. Callus proliferation medium with different concentrations of Amm...

  10. Persistence and transformation of the herbicide (/sup 14/C)glufosinate-ammonium in prairie soils under laboratory conditions

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.E.

    The degradation of the herbicide (/sup 14/C)glufosinate-ammonium (the ammonium salt of DL-homoalanin-4-ylmethylphosphinic acid), at a rate of 2 ppm, was studied in three prairie soils at 85% of their field capacity moisture at both 20 and 10/sup 0/C. In all soils the herbicide was biologically transformed to degradation product(s) that underwent further slow degradation with release of (/sup 14/C)carbon dioxide. At 20/sup 0/C, the soil half-life values for the (/sup 14/C)herbicide were 3-7 days and, at 10/sup 0/C, 8-11 days. Over a 90-day incubation period at 20/sup 0/C, between 28 and 55% of the applied radioactivity was released from treated soils as (/sup 14/C)carbon dioxide; solvent-extractable degradation product(s) accounted for 19-37% of the applied radioactivity; between 2.4 and 9.5% of the initial /sup 14/C was incorporated into soil microbial biomass and 7-13% into the fulvic, humic, and humin soil fractions.

  11. [Determination of glufosinate residue in tea by liquid chromatography-tandem mass spectrometry coupled with precolumn derivatization].

    Science.gov (United States)

    Lin, Yonghui; Liu, Zhengcai; Yang, Fang; Qiu, Yuanjin; Liu, Suzhen; Su, Zhijiao; Zhang, Qiong; Xue, Zhimin; Fang, Yu

    2012-12-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the determination of glufosinate (GLUF) residue in tea. The GLUF was extracted with water for 30 min under ultrasonication, and cleaned-up using a C18 solid phase extraction cartridge, then derived using fluorenylmethylchloroformate (FMOC-Cl) in borate buffer for 2 h. The separation was performed on a Kinetex C18 column with the mobile phases of acetonitrile and 5 mmol/L ammonium acetate aqueous solution (containing 0.2% (v/v) formic acid) in a gradient elution mode. The identification and quantification of the GLUF were carried out by MS/MS in negative electrospray ionization (ESI(-)) and multiple reaction monitoring (MRM) mode, the quantification analysis was performed by external standard method. The calibration curve showed good linearity in the range of 2.5 - 50.0 microg/L with the correlation coefficient r2 > 0.999. The limit of quantification (LOQ) was 0.10 mg/kg. The average recoveries of GLUF spiked at 0.10, 0.50 and 1.00 mg/kg levels in tea were between 61.6% and 81.4%, and the relative standard deviations (RSDs) were between 3.2% and 8.4%. The method is simple, rapid, sensitive, accurate and suitable for the confirmation and quantification of GLUF in tea.

  12. Persistence and transformation of the herbicide [14C]glufosinate-ammonium in prairie soils under laboratory conditions

    International Nuclear Information System (INIS)

    Smith, A.E.

    1988-01-01

    The degradation of the herbicide [ 14 C]glufosinate-ammonium (the ammonium salt of DL-homoalanin-4-ylmethylphosphinic acid), at a rate of 2 ppm, was studied in three prairie soils at 85% of their field capacity moisture at both 20 and 10 0 C. In all soils the herbicide was biologically transformed to degradation product(s) that underwent further slow degradation with release of [ 14 C]carbon dioxide. At 20 0 C, the soil half-life values for the [ 14 C]herbicide were 3-7 days and, at 10 0 C, 8-11 days. Over a 90-day incubation period at 20 0 C, between 28 and 55% of the applied radioactivity was released from treated soils as [ 14 C]carbon dioxide; solvent-extractable degradation product(s) accounted for 19-37% of the applied radioactivity; between 2.4 and 9.5% of the initial 14 C was incorporated into soil microbial biomass and 7-13% into the fulvic, humic, and humin soil fractions

  13. Toxicity of a glufosinate- and several glyphosate-based herbicides to juvenile amphibians from the Southern High Plains, USA.

    Science.gov (United States)

    Dinehart, Simon K; Smith, Loren M; McMurry, Scott T; Anderson, Todd A; Smith, Philip N; Haukos, David A

    2009-01-15

    Pesticide toxicity is often proposed as a contributing factor to the world-wide decline of amphibian populations. We assessed acute toxicity (48 h) of a glufosinate-based herbicide (Ignite 280 SL) and several glyphosate-based herbicide formulations (Roundup WeatherMAX, Roundup Weed and Grass Killer Super Concentrate, Roundup Weed and Grass Killer Ready-To-Use Plus on two species of amphibians housed on soil or moist paper towels. Survival of juvenile Great Plains toads (Bufo cognatus) and New Mexico spadefoots (Spea multiplicata) was reduced by exposure to Roundup Weed and Grass Killer Ready-To-Use Plus on both substrates. Great Plains toad survival was also reduced by exposure to Roundup Weed and Grass Killer Super Concentrate on paper towels. New Mexico spadefoot and Great Plains toad survival was not affected by exposure to the two agricultural herbicides (Roundup WeatherMAX and Ignite 280 SL) on either substrate, suggesting that these herbicides likely do not pose an immediate risk to these species under field conditions.

  14. Sublethal effects of the herbicide glufosinate ammonium on crops and wild plants: short-term effects compared to vegetative recovery and plant reproduction.

    Science.gov (United States)

    Carpenter, David; Boutin, Céline

    2010-10-01

    Current guidelines for phytotoxicity testing rely heavily on short-term testing of primarily crop species to predict the sensitivity of non-target, wild plants to herbicides. However, little is known on how plants recover following initial growth inhibitions in standard 14-28 day greenhouse tests conducted for pesticide assessment and registration. The objectives of this study were to assess the ability of plant species to recover (biomass and reproduction) when tested at the juvenile stage (routine regulatory testing), comparing crop and wild species and using the herbicide glufosinate ammonium. Ten crops and 10 wild species were tested with a one-time exposure to glufosinate ammonium in a greenhouse. Half the plants of each species (9 doses × 6 replicates) were harvested 3 weeks after being sprayed (short-term). The remaining plants were harvested several weeks later, coinciding with seed set or natural senescence (long-term). Total aboveground biomass and several endpoints related to crop production and plant reproduction were measured. Calculated IC50 values (dosage that results in a 50% decrease in the biomass of a plant as compared to the untreated controls) based solely on aboveground biomass, for species harvested in the long-term were generally higher than those obtained in the short-term (with two exceptions), indicating recovery over time. Crop species did not differ from wild species in terms of sensitivity. However, in seven out of 12 cases where reproduction was measurable, reproductive endpoints were more sensitive than either short or long-term biomass endpoints, indicating the importance of examining these parameters in phytotoxicity testing. Glufosinate ammonium was found to be phytotoxic at low doses (2.64-7.74% g ai/ha of the label rate).

  15. A review of methods for the analysis of orphan and difficult pesticides: glyphosate, glufosinate, quaternary ammonium and phenoxy acid herbicides, and dithiocarbamate and phthalimide fungicides.

    Science.gov (United States)

    Raina-Fulton, Renata

    2014-01-01

    This article reviews the chromatography/MS methodologies for analysis of pesticide residues of orphan and difficult chemical classes in a variety of sample matrixes including water, urine, blood, and food. The review focuses on pesticide classes that are not commonly included in multiresidue analysis methods such as highly polar or ionic herbicides including glyphosate, glufosinate, quaternary ammonium, and phenoxy acid herbicides, and some of their major degradation or metabolite products. In addition, dithiocarbamate and phthalimide fungicides, which are thermally unstable and have stability issues in some solvents or sample matrixes, are also examined due to their special needs in residue analysis.

  16. Sensibilidade de indivíduos e progênies de bidens pilosa e conyza sumatrensis ao amônio glufosinate

    OpenAIRE

    Brito, Ivana Paula Ferraz Santos de [UNESP

    2016-01-01

    A sensibilidade de plantas daninhas a herbicidas frequentemente se apresenta variável, em função de diversos fatores. O herbicida amônio glufosinate tem ação de contato e inibe a atividade da enzima glutamina sintetase, causando dentre outros efeitos, o acúmulo de amônia nos tecidos foliares, sendo esse um bom indicativo da intoxicação das plantas. Desse modo, o objetivo desse trabalho foi identificar a resposta de plantas de Bidens pilosa e Conyza sumatrensis a diferentes doses do herbicida ...

  17. MRI characterization of structural mouse brain changes in response to chronic exposure to the glufosinate ammonium herbicide.

    Science.gov (United States)

    Meme, Sandra; Calas, André-Guilhem; Montécot, Céline; Richard, Oliver; Gautier, Hélène; Gefflaut, Thierry; Doan, Bich Thuy; Même, William; Pichon, Jacques; Beloeil, Jean-Claude

    2009-10-01

    Glufosinate ammonium (GLA) is the active component of herbicides widely used in agriculture, truck farming, or public domains. GLA acts by inhibiting the plant glutamine synthetase (GlnS). It also inhibits mammalian GlnS in vitro and ex vivo. In the central nervous system this enzyme is exclusively localized in glial cells. Whereas acute neurotoxic effects of GLA are well documented, long-term effects during chronic exposure at low doses remain largely undisclosed. In the present work, C57BL/6J mice were treated intraperitoneally with 2.5, 5, and 10 mg/kg of GLA three times a week during 10 weeks. Cerebral magnetic resonance imaging (MRI) experiments were performed at high field (9.4 T) and the images were analyzed with four texture analysis (TA) methods. TA highlighted structural changes in seven brain structures after chronic GLA treatments. Changes are dose dependent and can be seen at a dose as low as 2.5 mg/kg for two areas, namely hippocampus and somatosensorial cortex. Glial fibrillary acidic protein (GFAP) expression in the same seven brain structures and GlnS activity in the hippocampus and cortex areas were also studied. The number of GFAP-positive cells is modified in six out of the seven areas examined. GlnS activity was significantly increased in the hippocampus but not in the cortex. These results indicate some kind of suffering at the cerebral level after chronic GLA treatment. Changes in TA were compared with the modification of the number of GFAP-positive astrocytes in the studied brain areas after GLA treatment. We show that the noninvasive MRI-TA is a sensitive method and we suggest that it would be a very helpful tool that can efficiently contribute to the detection of cerebral alterations in vivo during chronic exposure to xenobiotics.

  18. Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

    Science.gov (United States)

    Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

    2008-07-01

    Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

  19. Molecular investigations of the soil, rhizosphere and transgenic glufosinate-resistant rape and maize plants in combination with herbicide (Basta) application under field conditions.

    Science.gov (United States)

    Ernst, Dieter; Rosenbrock-Krestel, Hilkea; Kirchhof, Gudrun; Bieber, Evi; Giunaschwili, Nathela; Müller, Rüdiger; Fischbeck, Gerhard; Wagner, Tobias; Sandermann, Heinrich; Hartmann, Anton

    2008-01-01

    A field study was conducted during 1994 to 1998 on the Experimental Farm Roggenstein, near Fürstenfeldbruck, Bavaria, Germany to determine the effect of transgenic glufosinate-resistant rape in combination with the herbicide Basta [glufosinate-ammonium, phosphinothricin, ammonium (2RS)-2-amino-4-(methylphosphinato) butyric acid] application on soil microorganisms and the behaviour of the synthetic transgenic DNA in response to normal agricultural practice. No influence of Basta on microbial biomass could be detected. The phospholipid fatty acid analysis of soil extracts showed no difference between Basta application and mechanical weed control, whereas conventional herbicide application revealed a different pattern. Basta application resulted in a changed population of weeds with a selective effect for Viola arvensis. During senescence, transgenic rape DNA was degraded similar to endogenous control DNA. After ploughing the chopped plant material in the soil, transgenic as well as endogenous control DNA sequences could be detected for up to 4 weeks for rape and up to 7 months for maize, whereas PCR analysis of composted transgenic maize revealed the presence of the transgene over a period of 22 months.

  20. Biolistic co-transformation of Metarhizium anisopliae var. acridum strain CG423 with green fluorescent protein and resistance to glufosinate ammonium.

    Science.gov (United States)

    Inglis, P W; Aragão, F J; Frazão, H; Magalhães, B P; Valadares-Inglis, M C

    2000-10-15

    Metarhizium anisopliae var. acridum (syn. M. flavoviride) is recognized as a highly specific and virulent mycopathogen of locusts and grasshoppers and is currently being developed as a biological control agent for this group of insects in Brazil. Intact conidia of M. anisopliae var. acridum strain CG423 were transformed using microparticle bombardment. Plasmids used were: (1) pBARKS1 carrying the bar gene of Streptomyces hygroscopicus fused to the Aspergillus nidulans trpC promoter, encoding resistance to glufosinate ammonium (or phosphinothricin) and modified by addition of the telomeric repeat (TTAGGG)(18) of Fusarium oxysporum and 2.pEGFP/gpd/tel carrying a red-shifted variant gene for Aequorea victoria green fluorescent protein (EGFP) which we have fused to the A. nidulans gpd promoter and trpC terminator. Highly fluorescent co-transformants were selected on solid minimal medium containing 100 microg ml(-1) glufosinate ammonium using an inverted microscope with 450-490 nm excitation/510 nm emission filter set. Southern blot analysis of co-transformants revealed varying multiple chromosomal integrations of both bar and egfp genes at both telomeric and non-telomeric loci. Transformants retained pathogenicity in bioassays against Rhammatocerus schistocercoides and showed unaltered lack of pathogenicity against larvae of the non-target insect Anticarsia gemmatalis. One co-transformant from four tested, however, showed a significant, but non-dose-dependent, elevation in virulence against Tenebrio molitor.

  1. Determination of Glyphosate, its Degradation Product Aminomethylphosphonic Acid, and Glufosinate, in Water by Isotope Dilution and Online Solid-Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry

    Science.gov (United States)

    Meyer, Michael T.; Loftin, Keith A.; Lee, Edward A.; Hinshaw, Gary H.; Dietze, Julie E.; Scribner, Elisabeth A.

    2009-01-01

    The U.S. Geological Survey method (0-2141-09) presented is approved for the determination of glyphosate, its degradation product aminomethylphosphonic acid (AMPA), and glufosinate in water. It was was validated to demonstrate the method detection levels (MDL), compare isotope dilution to standard addition, and evaluate method and compound stability. The original method USGS analytical method 0-2136-01 was developed using liquid chromatography/mass spectrometry and quantitation by standard addition. Lower method detection levels and increased specificity were achieved in the modified method, 0-2141-09, by using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The use of isotope dilution for glyphosate and AMPA and pseudo isotope dilution of glufosinate in place of standard addition was evaluated. Stable-isotope labeled AMPA and glyphosate were used as the isotope dilution standards. In addition, the stability of glyphosate and AMPA was studied in raw filtered and derivatized water samples. The stable-isotope labeled glyphosate and AMPA standards were added to each water sample and the samples then derivatized with 9-fluorenylmethylchloroformate. After derivatization, samples were concentrated using automated online solid-phase extraction (SPE) followed by elution in-line with the LC mobile phase; the compounds separated and then were analyzed by LC/MS/MS using electrospray ionization in negative-ion mode with multiple-reaction monitoring. The deprotonated derivatized parent molecule and two daughter-ion transition pairs were identified and optimized for glyphosate, AMPA, glufosinate, and the glyphosate and AMPA stable-isotope labeled internal standards. Quantitative comparison between standard addition and isotope dilution was conducted using 473 samples analyzed between April 2004 and June 2006. The mean percent difference and relative standard deviation between the two quantitation methods was 7.6 plus or minus 6.30 (n = 179), AMPA 9.6 plus or minus 8

  2. Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

    Directory of Open Access Journals (Sweden)

    Yun-Liang Cui

    2016-01-01

    Conclusions: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.

  3. Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism

    Directory of Open Access Journals (Sweden)

    Kerstin Gnirß

    2014-04-01

    Full Text Available The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.

  4. Antagonism in the carbon footprint between beef and dairy ...

    African Journals Online (AJOL)

    The higher increase in production (milk) of intensive dairy cows, compared to the increase in production (calf weight) of intensive beef cows, explains the antagonism in the carbon footprint between different beef and dairy production systems. Unfortunately, carbon sequestration estimates have been neglected and thus the ...

  5. Exploitative and hierarchical antagonism in a cooperative bacterium.

    Directory of Open Access Journals (Sweden)

    Francesca Fiegna

    2005-11-01

    Full Text Available Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form of outright antagonism or social exploitation. Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation. Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations. Strains were competed against one another in all possible pairwise combinations during starvation-induced development. In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction. Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations. In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation. This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates. Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy. At least some competition pairs construct chimeric, rather than segregated, fruiting bodies. The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species. Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local

  6. Cardiovascular effects of a herbicide containing glufosinate and a surfactant: in vitro and in vivo analyses in rats.

    Science.gov (United States)

    Koyama, K; Koyama, K; Goto, K

    1997-08-01

    A herbicide, Basta (BASTA), containing glufosinate ammonium (GLA) as the main component and an anionic surfactant, sodium polyoxyethylene alkylether sulfate (AES), causes hemodynamic changes characterized by a decrease in total vascular resistance with an increase or a decrease in cardiac output in human acute oral poisoning. With a motivation based on these clinical observations, we tried to elucidate the exact component and its mode of action that is mostly responsible for the direct cardiovascular effects of this herbicide formulation, investigating the effects of BASTA, GLA, and AES independently on the cardiovascular system in rats in vitro and in vivo. In isolated right atria beating spontaneously in Krebs-Ringer's solution, BASTA and AES produced negative chronotropic responses in a concentration-dependent manner. In electrically driven isolated left atria, BASTA and AES produced positive inotropic responses concentration dependently but negative inotropic responses at extremely high concentrations. In aortic ring segments, BASTA and AES produced no vasoconstrictive effects but exerted significant vasodilative effects when the aortic ring was precontracted with phenylephrine. These in vitro responses caused by BASTA and AES occurred to a similar degree. On the other hand, the main component, GLA, produced no effects in isolated atria and aortas. In anesthetized rats, relatively low doses of BASTA and AES produced a decrease in blood pressure followed by a slight increase in heart rate, which was presumably due to baroreflex caused by the decrease in blood pressure. At an extremely high dose, BASTA and AES produced a decrease in blood pressure with a marked decrease in heart rate. These in vivo responses to BASTA and AES also occurred to a similar degree. In contrast, the main component, GLA, did not produce any effects on heart rate and blood pressure in anesthetized rats. From these results, we concluded that the effects of BASTA in our in vivo experiments

  7. Integrated Palmer Amaranth Management in Glufosinate-Resistant Cotton: I. Soil-Inversion, High-Residue Cover Crops and Herbicide Regimes

    Directory of Open Access Journals (Sweden)

    Michael G. Patterson

    2012-11-01

    Full Text Available A three year field experiment was conducted to evaluate the role of soil-inversion, cover crops and herbicide regimes for Palmer amaranth between-row (BR and within-row (WR management in glufosinate-resistant cotton. The main plots were two soil-inversion treatments: fall inversion tillage (IT and non-inversion tillage (NIT. The subplots were three cover crop treatments: crimson clover, cereal rye and winter fallow; and sub subplots were four herbicide regimes: preemergence (PRE alone, postemergence (POST alone, PRE + POST and a no herbicide check (None. The PRE herbicide regime consisted of a single application of pendimethalin at 0.84 kg ae ha−1 plus fomesafen at 0.28 kg ai ha−1. The POST herbicide regime consisted of a single application of glufosinate at 0.60 kg ai ha−1 plus S-metolachlor at 0.54 kg ai ha−1 and the PRE + POST regime combined the prior two components. At 2 weeks after planting (WAP cotton, Palmer amaranth densities, both BR and WR, were reduced ≥90% following all cover crop treatments in the IT. In the NIT, crimson clover reduced Palmer amaranth densities >65% and 50% compared to winter fallow and cereal rye covers, respectively. At 6 WAP, the PRE and PRE + POST herbicide regimes in both IT and NIT reduced BR and WR Palmer amaranth densities >96% over the three years. Additionally, the BR density was reduced ≥59% in no-herbicide (None following either cereal rye or crimson clover when compared to no-herbicide in the winter fallow. In IT, PRE, POST and PRE + POST herbicide regimes controlled Palmer amaranth >95% 6 WAP. In NIT, Palmer amaranth was controlled ≥79% in PRE and ≥95% in PRE + POST herbicide regimes over three years. POST herbicide regime following NIT was not very consistent. Averaged across three years, Palmer amaranth controlled ≥94% in PRE and PRE + POST herbicide regimes regardless of cover crop. Herbicide regime effect on cotton yield was highly significant; the maximum cotton yield was

  8. Platformed antagonism: Racist discourses on fake Muslim Facebook pages

    DEFF Research Database (Denmark)

    Farkas, Johan; Schou, Jannick; Neumayer, Christina

    2018-01-01

    This research examines how fake identities on social media create and sustain antagonistic and racist discourses. It does so by analysing 11 Danish Facebook pages, disguised as Muslim extremists living in Denmark, conspiring to kill and rape Danish citizens. It explores how anonymous content...... producers utilize Facebook's socio-technical characteristics to construct, what we propose to term as, platformed antagonism. This term refers to socio-technical and discursive practices that produce new modes of antagonistic relations on social media platforms. Through a discourse-theoretical analysis...... of posts, images, 'about' sections and user comments on the studied Facebook pages, the article highlights how antagonism between ethno-cultural identities is produced on social media through fictitious social media accounts, prompting thousands of user reactions. These findings enhance our current...

  9. Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals

    OpenAIRE

    Urwyler, Sandrine Andrea; Schuetz, Philipp; Ebrahimi, Fahim; Donath, Marc Y.; Christ-Crain, Mirjam

    2017-01-01

    Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH).; We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels.; In this prospective intervention study, we included 73 patients with obesity (b...

  10. Antagonism of Innate Immunity by Paramyxovirus Accessory Proteins

    Directory of Open Access Journals (Sweden)

    Raychel Chambers

    2009-10-01

    Full Text Available Paramyxovirinae, a subfamily of Paramyxoviridae, are negative strand RNA viruses comprised of many important human and animal pathogens, which share a high degree of genetic and structural homology. The accessory proteins expressed from the P/V/C gene are major factors in the pathogenicity of the viruses, because of their ability to abrogate various facets of type I interferon (IFN induction and signaling. Most of the paramyxoviruses exhibit a commonality in their ability to antagonize innate immunity by blocking IFN induction and the Jak/STAT pathway. However, the manner in which the accessory proteins inhibit the pathway differs among viruses. Similarly, there are variations in the capability of the viruses to counteract intracellular detectors (RNA helicases, mda-5 and RIG-I. Furthermore, a functional specificity in the antagonism of the IFN response has been reported, suggesting that specificity in the circumvention of innate immunity restricts viral host range. Available evidence indicates that paramyxoviruses employ specific strategies to antagonize the IFN response of their specific hosts, which is one of the major factors that determine viral pathogenicity and host range.

  11. Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

    Science.gov (United States)

    Urwyler, Sandrine Andrea; Schuetz, Philipp; Ebrahimi, Fahim; Donath, Marc Y; Christ-Crain, Mirjam

    2017-05-01

    Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate. Copyright © 2017 Endocrine Society

  12. Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic.

    Science.gov (United States)

    Patat, A; Naef, M M; van Gessel, E; Forster, A; Dubruc, C; Rosenzweig, P

    1994-10-01

    Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. Vigilance and performance were assessed by a trained anesthetist with use of ciliary reflex, response to a verbal instruction, subjective sedation, a tracking task, and a free recall task. Zolpidem produced a clinically relevant hypnotic effect in five subjects and significantly impaired performance in all nine subjects up to 90 minutes after dosing. Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.

  13. Calcitonin gene-related peptide antagonism and cluster headache

    DEFF Research Database (Denmark)

    Ashina, Håkan; Newman, Lawrence; Ashina, Sait

    2017-01-01

    Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact...... role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide......" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play...

  14. Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2014-12-01

    Full Text Available Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR. Host PRR for RNA viruses include Toll-like receptors (TLR and retinoic acid-inducible gene I (RIG-I like receptors (RLR. Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses.

  15. Extinction antagonizes olfactory memory at the subcellular level.

    Science.gov (United States)

    Schwaerzel, Martin; Heisenberg, Martin; Zars, Troy

    2002-08-29

    Memory loss occurs by diverse mechanisms, as different time constants of performance decrement and sensitivities to experimental manipulations suggest. While the phenomena of memory decay, interference, and extinction are well established behaviorally, little is known about them at the circuit or molecular level. In Drosophila, odorant memories lasting up to 3 hr can be localized to mushroom body Kenyon cells, a single neuronal level in the olfactory pathway. The plasticity underlying this memory trace can be induced without Kenyon cell synaptic output. Experimental extinction, i.e., presentation of the conditioned stimulus without the reinforcer, reduces memory performance and does so at the same circuit level as memory formation. Thus, unreinforced presentation of learned odorants antagonizes intracellularly the signaling cascade underlying memory formation.

  16. Safety evaluation of the phosphinothricin acetyltransferase proteins encoded by the pat and bar sequences that confer tolerance to glufosinate-ammonium herbicide in transgenic plants.

    Science.gov (United States)

    Hérouet, Corinne; Esdaile, David J; Mallyon, Bryan A; Debruyne, Eric; Schulz, Arno; Currier, Thomas; Hendrickx, Koen; van der Klis, Robert-Jan; Rouan, Dominique

    2005-03-01

    Transgenic plant varieties, which are tolerant to glufosinate-ammonium, were developed. The herbicide tolerance is based upon the presence of either the bar or the pat gene, which encode for two homologous phosphinothricin acetyltransferases (PAT), in the plant genome. Based on both a review of published literature and experimental studies, the safety assessment reviews the first step of a two-step-approach for the evaluation of the safety of the proteins expressed in plants. It can be used to support the safety of food or feed products derived from any crop that contains and expresses these PAT proteins. The safety evaluation supports the conclusion that the genes and the donor microorganisms (Streptomyces) are innocuous. The PAT enzymes are highly specific and do not possess the characteristics associated with food toxins or allergens, i.e., they have no sequence homology with any known allergens or toxins, they have no N-glycosylation sites, they are rapidly degraded in gastric and intestinal fluids, and they are devoid of adverse effects in mice after intravenous administration at a high dose level. In conclusion, there is a reasonable certainty of no harm resulting from the inclusion of the PAT proteins in human food or in animal feed.

  17. [Establisment of a genetic transformation method of coffee (Coffea arabica cv. Catimor) and incorporation of bar gene for ammonium glufosinate resistance].

    Science.gov (United States)

    Fernández Da Silva, Rafael

    2003-01-01

    In order to establish a successful method of genetic transformation in Coffea arabica cv. Catimor, different conditions of generation and electroporation were evaluated on different plant tissues. Cell suspension system was improved using one hormone only (BA), obtaining high yields of primary and secondary somatic embryo production. For selection of viable and potentially transformed cells, MTT (1%) method and ammonium glufosinate concentration (1 mg/L in leaf, callus and embryos; and 5 mg/L in cells) were established. Different conditions were evaluated to electroporate different explants (embryogenic callus, vitroplants leaves, globular and torpedo embryos). The highest gus gene expression percentage by explant were found on enzymatic treated tissues at 375 V/cm in callus, and at 625 V/cm in leaves and embryos. Torpedo embryos cultured on liquid medium were the only type of tissue that could regenerate into plants, where secondary somatic embryos were obtained. Those embryos were positive to the gus gene histochemical test and to the gus and bar genes amplification on a PCR reaction.

  18. Evaluation of the effects and mechanisms of action of glufosinate, an organophosphate insecticide, on striatal dopamine release by using in vivo microdialysis in freely moving rats.

    Science.gov (United States)

    Ferreira Nunes, Brenda V; Durán, Rafael; Alfonso, Miguel; de Oliveira, Iris Machado; Ferreira Faro, Lilian R

    2010-10-01

    The purpose of the present work was to assess the effects of glufosinate ammonium (GLA), an aminoacid structurally related to glutamate, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to HPLC-EC. Intrastriatal administration of GLA produced significant concentration-dependent increases in DA levels. At least two mechanisms can be proposed to explain these increases: GLA could be inducing DA release from synaptic vesicles or producing an inhibition of DA transporter (DAT). Thus, we investigated the effects of GLA under Ca(++)-free condition, and after pretreatment with reserpine and TTX. It was observed that the pretreatment with Ca(++)-free Ringer, reserpine or TTX significantly reduced the DA release induced by GLA. Coinfusion of GLA and nomifensine shows that the GLA-induced DA release did not involve the DAT. These results show that GLA-induced striatal DA release is probably mediated by an exocytotic-, Ca(++)-, action potential-dependent mechanism, being independent of DAT.

  19. The evolution of reduced antagonism--A role for host-parasite coevolution.

    Science.gov (United States)

    Gibson, A K; Stoy, K S; Gelarden, I A; Penley, M J; Lively, C M; Morran, L T

    2015-11-01

    Why do some host-parasite interactions become less antagonistic over evolutionary time? Vertical transmission can select for reduced antagonism. Vertical transmission also promotes coevolution between hosts and parasites. Therefore, we hypothesized that coevolution itself may underlie transitions to reduced antagonism. To test the coevolution hypothesis, we selected for reduced antagonism between the host Caenorhabditis elegans and its parasite Serratia marcescens. This parasite is horizontally transmitted, which allowed us to study coevolution independently of vertical transmission. After 20 generations, we observed a response to selection when coevolution was possible: reduced antagonism evolved in the copassaged treatment. Reduced antagonism, however, did not evolve when hosts or parasites were independently selected without coevolution. In addition, we found strong local adaptation for reduced antagonism between replicate host/parasite lines in the copassaged treatment. Taken together, these results strongly suggest that coevolution was critical to the rapid evolution of reduced antagonism. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  20. Cooperation, Trust, and Antagonism: How Public Goods Are Promoted.

    Science.gov (United States)

    Parks, Craig D; Joireman, Jeff; Van Lange, Paul A M

    2013-12-01

    One of the most continually vexing problems in society is the variability with which citizens support endeavors that are designed to help a great number of people. In this article, we examine the twin roles of cooperative and antagonistic behavior in this variability. We find that each plays an important role, though their contributions are, understandably, at odds. It is this opposition that produces seeming unpredictability in citizen response to collective need. In fact, we suggest that careful consideration of the research allows one to often predict when efforts to provide a collectively beneficial good will succeed and when they will fail. To understand the dynamics of participation in response to collective need, it is necessary to distinguish between the primary types of need situations. A public good is an entity that relies in whole or in part on contributions to be provided. Examples of public goods are charities and public broadcasting. Public goods require that citizens experience a short-term loss (of their contribution) in order to realize a long-term gain (of the good). However, because everyone can use the good once it is provided, there is also an incentive to not contribute, let others give, and then take advantage of their efforts. This state of affairs introduces a conflict between doing what is best for oneself and what is best for the group. In a public goods situation, cooperation and antagonism impact how one resolves this conflict. The other major type of need situation is a common-pool resource problem. Here, a good is fully provided at the outset, and citizens may sample from it. The resource is usually, but not necessarily, partially replenished. Examples of replenished resources are drinking water and trees; examples of resources that are functionally not replenished are oil and minerals. Common-pool resources allow citizens to experience a short-term gain (by getting what they want in the early life of the resource) but also present

  1. Kefiran antagonizes cytopathic effects of Bacillus cereus extracellular factors.

    Science.gov (United States)

    Medrano, Micaela; Pérez, Pablo Fernando; Abraham, Analía Graciela

    2008-02-29

    Kefiran, the polysaccharide produced by microorganisms present in kefir grains, is a water-soluble branched glucogalactan containing equal amounts of D-glucose and D-galactose. In this study, the effect of kefiran on the biological activity of Bacillus cereus strain B10502 extracellular factors was assessed by using cultured human enterocytes (Caco-2 cells) and human erythrocytes. In the presence of kefiran concentrations ranging from 300 to 1000 mg/L, the ability of B. cereus B10502 spent culture supernatants to detach and damage cultured human enterocytes was significantly abrogated. In addition, mitochondrial dehydrogenase activity was higher when kefiran was present during the cell toxicity assays. Protection was also demonstrated in hemolysis and apoptosis/necrosis assays. Scanning electron microscopy showed the protective effect of kefiran against structural cell damages produced by factors synthesized by B. cereus strain B10502. Protective effect of kefiran depended on strain of B. cereus. Our findings demonstrate the ability of kefiran to antagonize key events of B. cereus B10502 virulence. This property, although strain-specific, gives new perspectives for the role of bacterial exopolysaccharides in functional foods.

  2. Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism.

    Science.gov (United States)

    Zhang, H; Hu, G; Wang, H; Sciavolino, P; Iler, N; Shen, M M; Abate-Shen, C

    1997-05-01

    Protein-protein interactions are known to be essential for specifying the transcriptional activities of homeoproteins. Here we show that representative members of the Msx and Dlx homeoprotein families form homo- and heterodimeric complexes. We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. In particular, we show that Msx and Dlx proteins interact independently and noncooperatively with homeodomain DNA binding sites and that dimerization is specifically blocked by the presence of such DNA sites. We further demonstrate that the transcriptional properties of Msx and Dlx proteins display reciprocal inhibition. Specifically, Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. Finally, we show that the expression patterns of representative Msx and Dlx genes (Msx1, Msx2, Dlx2, and Dlx5) overlap in mouse embryogenesis during limb bud and craniofacial development, consistent with the potential for their protein products to interact in vivo. Based on these observations, we propose that functional antagonism through heterodimer formation provides a mechanism for regulating the transcriptional actions of Msx and Dlx homeoproteins in vivo.

  3. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism

    Directory of Open Access Journals (Sweden)

    Nathan H. Vande Burgt

    2015-10-01

    Full Text Available Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP, to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism.

  4. Antagonism of rice phylloplane fungi against Cercospora oryzae

    Science.gov (United States)

    Mardani, A.; Hadiwiyono

    2018-03-01

    Narrow brown leaf spot (NBLS) caused by Cercospora oryzae Miyake is one of the important obstacle in rice cultivation that can decrease the productivity up to 40%. It has been known well that some phylloplane fungi are antagonistic to some leaf diseases. Phylloplane fungi of rice however haven’t been studied much and poorly understood as biological control agent of rice pathogen such C. oryzae. The research aimed to study the antagonism of some phylloplane fungi of rice against C. oryzae. At least 14 isolates of phylloplane fungi were collected which consisted of six pathogenic and eight nonpathogenic variants. All of nonpathogenic isolates were antagonistic against C. oryzae both in vitro and only one isolate could not inhibit the infection of the pathogen in vivo. Some isolates were identified as Aspergillus, Mucor, Penicillium, Fusarium, and Trichoderma. The isolate of Mucor and Fusarium could inhibit the highest growth of pathogen on potato dextrose medium that were at 36.0% and 35.5% respectively. Whereas on artificial inoculation on rice, some isolates such Penicillium and Fusarium could inhibit most effectively and were significantly different to Mencozeb application with dosage 5g L-1.

  5. Caffeine antagonism of alcohol-induced driving impairment.

    Science.gov (United States)

    Liguori, A; Robinson, J H

    2001-07-01

    The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

  6. Notch pathway signaling in the skin antagonizes Merkel cell development.

    Science.gov (United States)

    Logan, Gregory J; Wright, Margaret C; Kubicki, Adam C; Maricich, Stephen M

    2018-02-15

    Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Degradation and leaching behaviour of 14C-glufosinate in a silty sand soil. Experiments in outdoor lysimeters with undisturbed soil cores

    International Nuclear Information System (INIS)

    Kubiak, R.

    1996-12-01

    Degradation and leaching behaviour of 14 C-labelled glufosinate in a silty sand soil was investigated in two outdoor lysimeters after repeated application of 12.5 litres/hectare (1/ha) Basta (divided in 7.5 and 5 l/ha respectively). The 14 C-loss during application was 4.8-8.2%. The 14 C-content in the plants (vines and weeds) was 0.3% of that applied at the most. After 130 days, 25.9 and 25.5% of the applied material was found in the soil up to a depth of 40 cm. One year after the first application, this amount was still 18.5 and 18.6%. As a consequence of the renewed spraying, the detected amounts of 14 C were 44.3 and 43.1% some 107 days after the first application in the second experimental year. The additional investigation in lysimeter 2 after 373 days showed a decrease to 33.9%. Most of the detected radioactivity remained in the 0-10 cm soil layer. At the end of the experiment, the amount of 14 C in the 30-40 cm layer was 0.5%. The total residues in the 0-10 cm soil layer were less than 1 mg/kg at all dates of sampling, and only a small amount still represented the free acid of the active ingredient. The average values were 0.05 mg/kg after 130 days, 0.01 mg/kg after 363 days and 0.09 mg/kg at the following date of sampling. In the spring of the following year, no residues of the free acid were detectable. The radioactivity in the percolate amounted to a maximum of 0.11% of that applied and in no case represented the free acid of the ammonium salt. (author)

  8. [Simultaneous determination of glyphosate and glufosinate-ammonium residues in tea by ultra performance liquid chromatography-tandem mass spectrometry coupled with pre-column derivatization].

    Science.gov (United States)

    Wu, Xiaogang; Chen, Xiaoquan; Xiao, Haijun; Liu, Binqiu

    2015-10-01

    A method was developed for the determination of glyphosate (GLY) and glufosinate-ammonium (GLUF) in tea using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample was extracted with ultrapure water and dichloromethane for 30 min under ultrasonication, followed by a simple cleanup with a C18 solid phase extraction (SPE) cartridge, and then GLY and GLUF were derivatized using 9-fluorenylmethoxycarbonyl (FMOC-Cl) in borate buffer for 2 h. The derivatives of GLY and GLUF were separated on a Waters C18 column (50 mm x 2.1 mm, 1.7 μm) in a gradient elution mode, and finally detected with positive electrospray ionization-mass spectrometry (ESI-MS/MS ) in multiple reaction monitoring (MRM) mode. The quantification analysis was performed by external standard method. The method showed a good linearity (r > 0. 990) in the range of 0.003 125-0.1 mg/L. The limits of detection (LODs) of GLY and GLUF were 0.03 mg/kg. At the spiked levels of 0.375, 1.5 and 4.5 mg/kg, the recoveries of GLY and GLUF were 87.37%-99.11% and 81.44% -86.17% respectively, and the relative standard deviations (RSDs) (n = 6) of GLY and GLUF were 0.68%-1.35% and 1.01%-2.33%, respectively. This method is simple, rapid and characterized with acceptable sensitivity and accuracy to meet the requirements for the analysis of GLY and GLUF simultaneously in tea.

  9. Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum.

    Science.gov (United States)

    Faro, Lilian R F; Ferreira Nunes, Brenda V; Alfonso, Miguel; Ferreira, Vania M; Durán, Rafael

    2013-09-15

    The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5. Administration of GLA to CNQX (500μM) pretreated animals produced an effect that was not significantly different from the one produced in animals not pretreated with CNQX. On the other hand, administration of GLA to l-NAME (100μM) or 7-NI (100μM) pretreated animals, produced increases in dopamine overflow that were ∼80% and ∼75% smaller than those observed in animals not pretreated with these inhibitors. In summary, GLA appears to act, at least in part, through an overstimulation of NMDA (and not AMPA/kainate) receptors with possible NO production to induce in vivo dopamine release. Administration of NMDA receptor antagonists and NOS inhibitors partially blocks the release of dopamine from rat striatum. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Degradation and leaching behaviour of {sup 14}C-glufosinate in a silty sand soil. Experiments in outdoor lysimeters with undisturbed soil cores

    Energy Technology Data Exchange (ETDEWEB)

    Kubiak, R

    1996-12-01

    Degradation and leaching behaviour of {sup 14}C-labelled glufosinate in a silty sand soil was investigated in two outdoor lysimeters after repeated application of 12.5 litres/hectare (1/ha) Basta (divided in 7.5 and 5 l/ha respectively). The {sup 14}C-loss during application was 4.8-8.2%. The {sup 14}C-content in the plants (vines and weeds) was 0.3% of that applied at the most. After 130 days, 25.9 and 25.5% of the applied material was found in the soil up to a depth of 40 cm. One year after the first application, this amount was still 18.5 and 18.6%. As a consequence of the renewed spraying, the detected amounts of {sup 14}C were 44.3 and 43.1% some 107 days after the first application in the second experimental year. The additional investigation in lysimeter 2 after 373 days showed a decrease to 33.9%. Most of the detected radioactivity remained in the 0-10 cm soil layer. At the end of the experiment, the amount of {sup 14}C in the 30-40 cm layer was 0.5%. The total residues in the 0-10 cm soil layer were less than 1 mg/kg at all dates of sampling, and only a small amount still represented the free acid of the active ingredient. The average values were 0.05 mg/kg after 130 days, 0.01 mg/kg after 363 days and 0.09 mg/kg at the following date of sampling. In the spring of the following year, no residues of the free acid were detectable. The radioactivity in the percolate amounted to a maximum of 0.11% of that applied and in no case represented the free acid of the ammonium salt. (author)

  11. Induction of micronuclei and nuclear abnormalities in tadpoles of the common toad (Rhinella arenarum) treated with the herbicides Liberty® and glufosinate-ammonium.

    Science.gov (United States)

    Lajmanovich, Rafael C; Cabagna-Zenklusen, Mariana C; Attademo, Andrés M; Junges, Celina M; Peltzer, Paola M; Bassó, Agustín; Lorenzatti, Eduardo

    2014-07-15

    The assessment of micronucleated erythrocytes (ME) in blood represents a widely used method for the detection of chromosomal damage by chemical agents, such as herbicides that may occur as water contaminants. We investigated the changes in some circulating blood-cell parameters of tadpoles of the common toad (Rhinella arenarum) that were exposed during 48 or 96 h to three sub-lethal concentrations (3.75, 7.5, and 15 mg/L) of a commercial formulation of a glufosinate-ammonium (GLA)-based herbicide (Liberty(®), LY(®)) as well as to the corresponding active ingredient GLA. The frequency of ME and other erythrocyte nuclear abnormalities (ENA, i.e., lobed nuclei, binucleates or segmented nuclei, kidney-shaped nuclei, notched nuclei, and picnotic nuclei) were evaluated and compared with positive (cyclophosphamide, CP, 40 mg/L) and negative (de-chlorinated tap water) controls. The results indicate that the exposure of R. arenarum tadpoles to LY(®) induces a concentration-dependent increase in ME frequency. The ENA frequency at 48 h was also significantly higher than that in the negative control group for all the chemicals assayed (CP, LY(®) and GLA) whereas at 96 h, increases in ENA over the negative control group were found only for CP and GLA (7.5 mg/L). Our study demonstrates that the commercial formulation of a GLA-based herbicide induces micronucleus formation in R. arenarum tadpoles, in contrast to the active ingredient. According to these results, the inert ingredients of the commercial formulation played an important role in the production of genotoxic damage in erythrocytes of amphibian tadpoles. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Optimisation of tomato Micro-tom regeneration and selection on glufosinate/Basta and dependency of gene silencing on transgene copy number.

    Science.gov (United States)

    Khuong, Thi Thu Huong; Crété, Patrice; Robaglia, Christophe; Caffarri, Stefano

    2013-09-01

    An efficient protocol of transformation and selection of transgenic lines of Micro-tom, a widespread model cultivar for tomato, is reported. RNA interference silencing efficiency and stability have been investigated and correlated with the number of insertions. Given its small size and ease of cultivation, the tomato (Solanum lycopersicon) cultivar Micro-tom is of widespread use as a model tomato plant. To create and screen transgenic plants, different selectable markers are commonly used. The bar marker carrying the resistance to the herbicide glufosinate/Basta, has many advantages, but it has been little utilised and with low efficiency for identification of tomato transgenic plants. Here we describe a procedure for accurate selection of transgenic Micro-tom both in vitro and in soil. Immunoblot, Southern blot and phenotypic analyses showed that 100 % of herbicide-resistant plants were transgenic. In addition, regeneration improvement has been obtained by using 2 mg/l Gibberellic acid in the shoot elongation medium; rooting optimisation on medium containing 1 mg/l IAA allowed up to 97 % of shoots developing strong and very healthy roots after only 10 days. Stable transformation frequency by infection of leaf explants with Agrobacterium reached 12 %. Shoots have been induced by combination of 1 mg/l zeatin-trans and 0.1 mg/l IAA. Somatic embryogenesis of cotyledon on medium containing 1 mg/l zeatin + 2 mg/l IAA is described in Micro-tom. The photosynthetic psbS gene has been used as reporter gene for RNA silencing studies. The efficiency of gene silencing has been found equivalent using three different target gene fragments of 519, 398 and 328 bp. Interestingly, silencing efficiency decreased from T0 to the T3 generation in plants containing multiple copies of the inserted T-DNA, while it was stable in plants containing a single insertion.

  13. Determination of glufosinate ammonium and its metabolite (AE F064619 and AE F061517) residues in water by gas chromatography with tandem mass spectrometry after ion exchange cleanup and derivatization.

    Science.gov (United States)

    Royer, A; Beguin, S; Sochor, H; Communal, P Y

    2000-11-01

    An analytical method for the determination of glufosinate ammonium and its principal metabolites, AE F064619 and AE F061517, in water of two different hardnesses (5 and 30 DH, French hardness) has been developed and validated. Samples were spiked at different levels (0. 05 and 0.5 microgram/L) and were purified by column chromatography on ion-exchange resins. After derivatization with glacial acetic acid and trimethylarthoacetate mixture, the derivatives were quantified by using capillary gas chromatography with an ion-trap tandem mass spectrometric detector. Analytical conditions for MS/MS detection were optimized, and the quantification was carried out on the areas of the most representative ions. The limit of quantification was validated at 0.05 microgram/L for each compound. The mean recovery value and the relative standard deviation (n = 20) were 92.0% and 17. 8% for glufosinate ammonium, 90.2% and 15.8% for AE F064619, and 89. 7% and 12.7% for AE F061517.

  14. APETALA 2-domain-containing transcription factors: focusing on abscisic acid and gibberellins antagonism.

    Science.gov (United States)

    Shu, Kai; Zhou, Wenguan; Yang, Wenyu

    2018-02-01

    The phytohormones abscisic acid (ABA) and gibberellin (GA) antagonistically mediate diverse plant developmental processes including seed dormancy and germination, root development, and flowering time control, and thus the optimal balance between ABA and GA is essential for plant growth and development. Although more than a half and one century have passed since the initial discoveries of ABA and GA, respectively, the precise mechanisms underlying ABA-GA antagonism still need further investigation. Emerging evidence indicates that two APETALA 2 (AP2)-domain-containing transcription factors (ATFs), ABI4 in Arabidopsis and OsAP2-39 in rice, play key roles in ABA and GA antagonism. These two transcription factors precisely regulate the transcription pattern of ABA and GA biosynthesis or inactivation genes, mediating ABA and GA levels. In this Viewpoint article, we try to shed light on the effects of ATFs on ABA-GA antagonism, and summarize the overlapping but distinct biological functions of these ATFs in the antagonism between ABA and GA. Finally, we strongly propose that further research is needed into the detailed roles of additional numerous ATFs in ABA and GA crosstalk, which will improve our understanding of the antagonism between these two phytohormones. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  15. Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

    Directory of Open Access Journals (Sweden)

    MIKI TSUJITA

    2007-01-01

    Full Text Available Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2. In the other experiment, apneic threshold PaC0(2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit

  16. Produção de prolina e suscetibilidade ao glufosinato de amônio em plantas transgênicas de citrumelo Swingle Proline production by transgenic plants of Swingle citrumelo and susceptibility to glufosinate ammonium

    Directory of Open Access Journals (Sweden)

    Cristine Elizabeth Alvarenga Carneiro

    2006-05-01

    Full Text Available O objetivo deste trabalho foi avaliar a sensibilidade de plantas transgênicas de citrumelo Swingle com elevada produção de prolina, ao herbicida glufosinato de amônio. As plantas utilizadas apresentavam a inserção do gene mutante da enzima delta1-pirrolina-5-carboxilato sintetase (P5CS, responsável pela biossíntese de prolina. A expressão do gene p5cs em plantas transgênicas causou aumento nas quantidades de prolina em tecidos foliares, em até cinco vezes, quando comparadas às plantas-controle tratadas com 200 µM de glufosinato de amônio. As plantas transgênicas acumularam maior quantidade de NH4+ nas folhas, em relação às plantas não-transgênicas. Os danos causados pelo herbicida foram avaliados in vitro, utilizando-se discos foliares cultivados em meio MS com diferentes concentrações de glufosinato de amônio. Observou-se maior clorose em discos foliares das plantas transgênicas, o que comprova a maior suscetibilidade de plantas de citrumelo Swingle com alta produção de prolina ao herbicida.The objective of this work was to evaluate the susceptibility to glufosinate ammonium of transgenic plants of Swingle citrumelo with high proline production. The mutant gene of the enzyme delta1-pyrroline-5-carboxylate synthetase (P5CS, the rate-limiting enzyme in proline biosynthesis, was inserted into Swingle citrumelo plants. The expression of the gene p5cs caused up to 5-fold increase on the proline content in leaf tissues of transgenic plants treated with 200 µM glufosinate ammonium, when compared with control plants. Leaves of transgenic plants accumulated higher amounts of NH4+ than the nontransgenic control. The herbicide toxicity was evaluated using leaf disks cultivated in MS medium, containing different concentrations of glufosinate ammonium. The severity of the chlorosis, observed in leaf disks of transgenic plants, confirmed the higher susceptibility of Swingle citrumelo plants, with high proline production, to this

  17. Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

    DEFF Research Database (Denmark)

    Johansen, H K; Jensen, T G; Dessau, R B

    2000-01-01

    The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize th...

  18. [Antagonism of Trichoderma spp. to fungi caused root rot of Sophora tonkinensis].

    Science.gov (United States)

    Qin, Liu-yan; Jiang, Ni; Tang, Mei-qiong; Miao, Jian-hua; Li, Lin-xuan

    2011-04-01

    To study the antagonism of Trichoderma spp. to fungi S9(Fusarium solani)which caused root rot of Sophora tonkinensis and discuss the further develop prospects of microbial biological control in soil-borne diseases on Chinese herbal medicines. Antagonism of H2 (Trichoderma harsianum), M6 (Trichoderma viride) and K1 (Trichoderma koningii) to Fusarium solani were researched by growth rate and confront culture. And their mechanisms were discussed. H2 and M6 had obvious competitive advantage, the growth rate of which were 1.43-2.72 times and 1.43-1.95 times as S9 respectively. The space competitive advantage of K1 was relatively weak; the growth rate was slower than S9. The antagonism of three species of Trichoderma spp. to S9 was in varying degrees. The antagonism to S9 of M6 and H2 was better,the inhibition rate were 100% and 82.35% respectively, even cultivated S9 for three days in advance. And their inhibition indexes were both reached class I. The inhibition index and inhibition rate of K1 was respectively 46.36% and class IV. The Trichoderma spp. could cause S9 mycelium to appear some phenomenon just like fracture, constriction reduced, digestion, etc. which were observed under the microscope. Trichoderma harsianum and Trichoderma viride showed the further develop prospects in the fight against soil-borne disease on Chinese herbal medicines.

  19. Mutualism and Antagonism: Ecological Interactions Among Bark Beetles, Mite and Fungi

    Science.gov (United States)

    K.D. Klepzig; J.C. Moser; M.J. Lombardero; M.P. Ayres; R.W. Hofstetter; C.J. Walkinshaw

    2001-01-01

    Insect-fungal complexes provide challenging and fascinating systems for the study of biotic interactions between plants. plant pathogens, insect vectors and other associated organisms. The types of interactions among these organisms (mutualism. antagonism. parasitism. phoresy. etc.) are as variable as the range of organisms involved (plants, fungi, insects. mites. etc...

  20. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    OpenAIRE

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif; Therkelsen, Ib; Borup, Rehannah; Nilsson, Elise; Multhaupt, Hinke; Bouchard, Caroline; Quistorff, Bjørn; Kjær, Andreas; Landberg, Göran; Staller, Peter

    2011-01-01

    This paper characterizes FoxO3A as required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production. Mechanistically, FoxO3A is shown to promote hypoxic cell survival by directly antagonizing c-Myc at nuclear encoded mitochondrial genes.

  1. Isolation, Characterization and Identification of Environmental Bacterial Isolates with Screening for Antagonism Against Three Bacterial Targets

    Science.gov (United States)

    2017-04-01

    ISOLATES WITH SCREENING FOR ANTAGONISM AGAINST THREE BACTERIAL TARGETS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Identification of environmental isolates followed the flowchart from “Bergey’s Manual of Determinative Bacteriology” (Holt et al. 1994), which

  2. Does gestrinone antagonize the effects of estrogen on endometrial implants upon the peritoneum of rats?

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Rodrigues Lobo

    2008-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of estrogen treatment in combination with gestrinone on an experimental rat model of endometriosis. METHODS: Uterine transplants were attached to the peritoneum of female Wistar rats via a surgical autotransplantation technique. The implanted area was measured during the proestrus phase and after hormonal treatment. We performed morphometric analysis and examined the macroscopic and morphometric alterations of endometrial implants after hormonal treatment in ovariectomized rats. RESULTS: The high dose of estrogen caused macroscopic increases in the endometrial implant group compared with other groups, which were similar to increases in the proestrus phase. The low dose showed morphometric development of implants, such as an increase in number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone antagonized both doses of estrogen. CONCLUSION: Our findings suggest that gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants.

  3. Complement C5a receptor antagonism by protamine and poly-L-Arg on human leukocytes.

    Science.gov (United States)

    Olsen, U B; Selmer, J; Kahl, J U

    1988-01-01

    It is shown that protamine selectively and dose-dependently inhibits complement C5a-induced leukocyte responses such as histamine release from basophils, chemiluminescence and beta-glucuronidase release from neutrophils. Protamine produces parallel rightward displacements of the C5a dose-response curves. The inhibitory capacity of the polypeptide is reversible and disappears following repeated washing of exposed cells. In neutrophils poly-L-Arg similarly and specifically antagonizes C5a-induced chemiluminescence and enzyme release. This polymer alone, however, degranulates basophils and neutrophils, leading to histamine and enzyme release, respectively. It is concluded that on human neutrophils the arginine-rich polycations protamine and poly-L-Arg exhibit a competitive C5a receptor antagonism. In addition, protamine inhibits the C5a receptors on basophils. It is hypothesized that molecular conformations of the arginine-rich polycations might bind reversibly to, and block negatively charged groups at the C5a-receptor sites.

  4. Potencial de cruzamento natural entre o arroz transgênico resistente ao herbicida glufosinato de amônio e o arroz daninho Outcrossing potential of glufosinate-resistant rice to red rice

    Directory of Open Access Journals (Sweden)

    J.A. Noldin

    2002-08-01

    Full Text Available A utilização de cultivares de arroz irrigado resistentes a herbicidas não-seletivos, como o glufosinato de amônio, pode se constituir numa alternativa de controle de arroz daninho em lavouras de arroz irrigado. O objetivo deste trabalho foi avaliar a taxa e o sentido do cruzamento natural entre plantas de uma linhagem modificada geneticamente para resistência ao herbicida glufosinato de amônio (arroz GM e ao arroz daninho. A taxa de cruzamento natural entre o arroz GM como receptor feminino e o arroz daninho como doador de pólen foi de 0,22 e 0,02%, respectivamente para os ecótipos de arroz daninho com glumas de cor palha e com glumas pretas. No caso inverso, quando o arroz daninho foi o receptor feminino e o arroz GM o doador de pólen, a taxa de cruzamento foi de 0,26 e 0,14%, para o arroz daninho com glumas palha e com glumas pretas, respectivamente. Os resultados deste estudo evidenciaram que ocorreu cruzamento natural entre o arroz GM e o arroz daninho em percentuais que variaram de 0,14 e 0,48%, respectivamente para o arroz preto e para o arroz vermelho. A fim de minimizar a possibilidade de hibridação, medidas de controle eficientes devem ser adotadas no sentido de prevenir a coincidência de floração das plantas de arroz daninho com a das plantas de arroz GM cultivado.The broad spectrum non-selective herbicide ammonium glufosinate, combined with genetically modified glufosinate-resistant rice cultivars (GM rice, may comprise a rice weed control system for red rice and other weeds that infest Brazilian rice fields. The objective of this study was to evaluate the potential for outcrossing and gene flow of GM rice to red rice. Natural outcrossing between adjacent field plots (1 m x 1 m was measured during the 1999/2000 production season in Brazil. The outcrossing rate of the GM rice as the female parent to red rice, as the pollen donor, was 0.22% for strawhull and 0.02% for the blackhull red rice, respectively. In the reciprocal

  5. [Antagonism in vitro among phytopathogenic and saprobic fungi from horticultural soils].

    Science.gov (United States)

    Alippi, H E; Monaco, C

    1990-01-01

    Two methods were tested in order to determine the existence of in vitro antagonism among saprobic and pathogenic fungi. These microorganisms were the most common isolates from horticultural soils of La Plata (Buenos Aires). Trichoderma harzianum; T. koningii and Penicillium sp. were antagonistic to all the pathogenic fungi tested, Fusarium solani; F. oxysporum; Alternaria solani; Colletotrichum sp. and Sclerotium rolfsii Spicaria sp., Paecilomyces sp. and Chaetomiun sp. were antagonistic only to Colletotrichum sp. and Fusarium solani.

  6. Evaluation of the antagonism of nicotine by mecamylamine and pempidine in the brain

    International Nuclear Information System (INIS)

    Martin, T.J.

    1989-01-01

    Antagonists have been crucial in the characterization of nicotine's pharmacology. Initial evidence for the existence of central nicotinic receptors was based on the fact that nicotine produced a number of behavioral effects that were antagonized by ganglionic blockers that crossed the blood-brain barrier, such as mecamylamine and pempidine. These compounds are thought to be noncompetitive antagonists due to the fact that they do not compete for agonist binding to brain homogenate in vitro. However, pharmacological evidence in support of noncompetitive antagonism is lacking. Dose-response curves for nicotine were determined in the presence of various doses of pempidine for depression of spontaneous activity and antinociception in mice. Pempidine was found to shift the dose response curves for these effects of nicotine in a manner consistent with noncompetitive antagonism. A number of mecamylamine analogs were investigated for antagonism of these central effects of nicotine as well. These studies revealed that the N-, 2-, and 3-methyls were crucial for optimal efficacy and potency and suggests that these compounds possess a specific mechanism of action, possibly involving a receptor. Furthermore, the structure-activity relationships for the mecamylamine analogs were found to be different than that previously reported for the agonists, suggesting that they do not act at the same site. The binding of [ 3 H]-L-nicotine and [ 3 H]-pempidine was studied in vitro to mouse brain homogentate and in situ to rat brain slices. The in situ binding of [ 3 H]-L-nicotine to rat brain slices was quantitated autoradiographically to discrete brain areas in the presence and absence of 1, 10 and 100 μM nicotine and pempidine. Pempidine did not effectively displace [ 3 H]-L-nicotine binding

  7. Desempenho de populações híbridas F2 de arroz-vermelho (Oryza sativa com arroz transgênico (O. sativa resistente ao herbicida amonio-glufosinate Performance of F2 hybrid populations of red rice (Oryza sativa with ammonium-glufosinate-resistant transgenic rice (O. sativa

    Directory of Open Access Journals (Sweden)

    J.A. Noldin

    2004-09-01

    -preto. Mesmo assim, os usuários dessa tecnologia deverão adotar, obrigatoriamente, medidas que evitem a possibilidade de cruzamento entre o arroz transgênico e o arroz-vermelho ou arroz-preto.Red rice is an important weed in paddy rice fields. The use of ammonium glufosinate - resistant genetically modified (GM rice cultivars is a viable alternative for controlling red rice in cultivated rice crops. The objective of this study was to evaluate the behavior of F2 hybrid population derivates of crossing between ammonium glufosinate - resistant GM rice and red rice. The F2 hybrid population derivates of crossing between GM rice and red rice are viable but do not present any apparent competitive advantage over red rice. The morphological characteristics of the F2 hybrid populations, such as tillering capacity, number of leaves produced and average plant height were partly reduced and partly unaffected by the introgression of the bar gene. The period between rice planting and 50% flowering increased in the red rice x GM rice F2 hybrids, compared to the parental red rice and GM rice. Average seed shattering rate in the four hybrid families was lower than in the red rice ecotypes, with such aspect also being unfavorable to the persistence of red rice in the environment. Seed dormancy of the hybrids was similar to that of the red rice ecotypes. However, management practices should be adopted to avoid crossing between transgenic rice and red rice.

  8. In vitro antagonism of Trichoderma harzianum Rifai against Mycosphaerella fijiensis Morelet

    Directory of Open Access Journals (Sweden)

    Mayra Acosta-Suárez

    2013-10-01

    Full Text Available The in vitro antagonism of Trichoderma harzianum against Mycosphaerella fijiensis, foliar pathogen of banana and plantain, was evaluated. The assays were performed using the dual culture method. Competition for space and nutrients, the antagonistic capacity and forms and intensity of antagonism were determined considering the invasion of the surface of the colony, colonization and sporulation of T. harzianum on M. fijiensis after seven days of inoculation. Finally, the effect of volatile metabolites of T. harzianum was evaluated. The results showed in vitro antagonism of T. harzianum against M. fijiensis by competition for space and nutrients of the culture medium. Trichoderma grew over the pathogen colony with hyperparasitism and high intensity. Also, it completely covered the surface of the culture medium. T. harzianum not inhibited the growth of M. fijiensis by volatile metabolites. Damage was observed in the integrity of the cell wall of M. fijiensis hyphae and the cell content exit. The use of antagonistic fungi, could contribute to the design of strategies for integrated management of this disease. Key words: banana and plantain, biocontrol, mechanisms of action

  9. Arctigenin antagonizes mineralocorticoid receptor to inhibit the transcription of Na/K-ATPase.

    Science.gov (United States)

    Cheng, Ye; Zhou, Meili; Wang, Yan

    2016-01-01

    Hypertension is one of the most important risk factors in cardiovascular disease and is the most common chronic disease. Mineralocorticoid receptor (MR) antagonists have been successfully used in clinic for the treatment of hypertension. Our study aims to investigate whether Arctigenin can antagonize MR and inhibit the transcription of Na/K-ATPase. The yeast two-hybrid assay was used to screen natural products and Arctigenin was identified as an MR antagonist. The direct binding of Arctigenin to MR was determined using assays based on surface plasmon resonance, differential scanning calorimetry and fluorescence quenching. Furthermore, results from mammalian one-hybrid and transcriptional activation experiments also confirmed that Arctigenin can potently antagonize MR in cells. We demonstrated that Arctigenin can decrease the level of Na/K-ATPase mRNA by antagonizing MR in HK-2 cells. Our findings show that Arctigenin can effectively decrease Na/K-ATPase transcription; thus highlight its potential as an anti-hypertensive drug lead compound. Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease.

  10. Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines

    International Nuclear Information System (INIS)

    D’Alessandro, Rosalba; Refolo, Maria G; Lippolis, Catia; Giannuzzi, Grazia; Carella, Nicola; Messa, Caterina; Cavallini, Aldo; Carr, Brian I

    2014-01-01

    Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions

  11. [Antagonism against Beauveria bassiana by lipopeptide metabolites produced by entophyte Bacillus amyloliquefaciens strain SWB16].

    Science.gov (United States)

    Wang, Jingjie; Zhao, Dongyang; Liu, Yonggui; Ao, Xiang; Fan, Rui; Duan, Zhengqiao; Liu, Yanping; Chen, Qianqian; Jin, Zhixiong; Wan, Yongji

    2014-07-04

    We screened bacterial strains that have strong antagonism against Beauveria bassiana, an important pathogen of silkworm industry, and detected the antagonistic activity of lipopeptide metabolites. We identified bacterium SWB16 by morphological observation, physiological and biochemical experiments, 16SrRNA, and gyrA gene sequence analysis, tested antagonistic activity of strain SWB16 against Beauveria bassiana by measuring the inhibition zone diameter using filter paper diffusion method (Kirby-Bauer method), obtained lipopeptide metabolites of the strain using methanol extraction and observed the antagonism of strain SWB16 lipopeptide extracts against the conidia and hyphae of Beauveria bassiana, detected main ingredients and genes of lipopeptide metabolites by high-performance liquid chromatography-mass spectrometry and PCR amplification. SWB16 isolated from tissue of plant Dioscorea zingiberensis C. H. Wright belongs to Bacillus amyloliquefaciens and showed high antagonistic activity to Beauveria bassiana, and the lipopeptide extracts of isolate SWB16 exhibited significant inhibition to conidial germination and mycelial growth of Beauveria bassiana. The result of mass spectrometric detection indicated main component of the lipopeptide metabolites were fengcin and iturin, and genes fenB, ituA involved in the synthesis of them were amplified in the genome. Bacillus amyloliquefaciens strain SWB16 could produce lipopeptide antibiotics with strong antagonism to the entomopathogenic fungus Beauveria bassiana, and the results suggested that strain SWB16 has potential application value for controlling white muscardine of economic insects including silkworm.

  12. 40 CFR 180.458 - Clethodim; tolerances for residues.

    Science.gov (United States)

    2010-07-01

    ... greens subgroup 4A 2.0 Melon subgroup 9A 2.0 Mustard, seed 0.50 Onion, bulb 0.20 Onion, green 2.0 Peach 0... Cattle, meat 0.2 Cattle, meat byproducts 0.2 Cotton, undelinted seed 1.0 Egg 0.2 Goat, fat 0.2 Goat, meat....7 Bean, dry, seed 2.5 Beet, sugar, molasses 1.0 Beet, sugar, roots 0.20 Beet, sugar, tops 1.0...

  13. Determination of glufosinate ammonium and its metabolite, 3-methylphosphinicopropionic acid, in human serum by gas chromatography-mass spectrometry following mixed-mode solid-phase extraction and t-BDMS derivatization.

    Science.gov (United States)

    Hori, Y; Fujisawa, M; Shimada, K; Hirose, Y

    2001-01-01

    A method for the analysis of glufosinate ammonium (GLUF) and its metabolite 3-methylphosphinicopropionic acid (MPPA) in human serum by gas chromatography-mass spectrometry (GC-MS) was developed. Employing a mixed-mode cartridge with both anion exchange action and weak nonpolar interaction, we extracted GLUF and MPPA from the serum and carried out GC-MS analysis of their tert-butyldimethylsilyl derivatives. The detection limits of GLUF and MPPA were 10 pg and 1 pg, respectively. Full mass spectra of 100 pg GLUF and of 10 pg MPPA were easily obtainable. The recovery rate of 90.0+/-11.9% (or better) when the serum concentrations of GLUF and MPPA were 10-0.1 microg/mL. Results of 23 serum samples, from patients with GLUF poisoning, measured by this method correlate well with those derived from the conventional high-performance liquid chromatography method (r = 0.996). The developed GC-MS method is likely to become a useful analytical technique in clinical settings.

  14. Antagonism of a (+)N-allylnormetazocine stimulus by (-)PPAP and several structurally related analogs.

    Science.gov (United States)

    Glennon, R A; Young, R; Herndon, J L

    1993-08-01

    Employing rats trained to discriminate 5 mg/kg of the benzomorphan opioid (+)N-allylnormetazocine [(+)NANM] from vehicle, tests of stimulus generalization and antagonism were conducted to determine the influence of several potential sigma-receptor ligands. It has been previously suggested that the (+)NANM stimulus may involve concurrent action at sigma- and phencyclidine (PCP) receptors. Although the low-affinity sigma-antagonist rimcazole was without stimulus-attenuating effect, three novel sigma-ligands--(-)PPAP, CNS 3018, and CNS 3093 (ID50 doses = 3.2, 6.7, and 4.5 mg/kg, respectively)--antagonized the (+)NANM stimulus in a dose-related fashion. The nonselective serotonergic agent 1-(3-trifluoromethyl)phenylpiperazine (TFMPP) produced partial generalization in (+)NANM-trained animals whereas buspirone, a 5-hydroxytryptamine1A (5-HT1A) agonist, attenuated (to 27% drug-appropriate responding) the (+)NANM stimulus. Because the prototypic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) failed to attenuate the (+)NANM stimulus at pharmacologically relevant doses, it seems unlikely that the (+)NANM stimulus involves a 5-HT1A mechanism. TFMPP and buspirone display modest affinity for sigma-receptors and this may account for the present findings with these agents. The present results neither establish a role for sigma involvement in the stimulus properties of (+)NANM nor eliminate a role for PCP receptors. They do, however, demonstrate that sigma-ligands with little to no affinity for PCP receptors are capable of antagonizing the (+)NANM stimulus.

  15. Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

    Science.gov (United States)

    Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

    2018-01-01

    The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

  16. Design of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) Trial.

    Science.gov (United States)

    Rajagopalan, Sanjay; Alaiti, M Amer; Broadwater, Kylene; Goud, Aditya; Gaztanaga, Juan; Connelly, Kim; Fares, Anas; Shirazian, Shayan; Kreatsoulas, Catherine; Farkouh, Michael; Dobre, Mirela; Fink, Jeffrey C; Weir, Matthew R

    2017-09-01

    Mineralocorticoid receptor (MR) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating MR antagonism in patients with type 2 diabetes mellitus (T2DM) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for MR antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that MR antagonism may provide additional protection from atherosclerosis progression in higher-risk patients who otherwise may not be candidates for such a therapeutic approach. In this double-blind, randomized, placebo-controlled trial, subjects with T2DM with chronic kidney disease (≥ stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4-week period). The co-primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24-hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (HOMA-IR) at 6 weeks. A novel measure in the study will be changes in candidate miRNAs that regulate expression of NR3C2 (MR gene) as well as measuring monocyte/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event-based trials. © 2017 Wiley Periodicals, Inc.

  17. Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

    Science.gov (United States)

    Khalaf, Eman M.; Raizada, Manish N.

    2018-01-01

    The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays) against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanideratum). The endophytes were also assayed in planta (leaf disk and detached leaf bioassays) for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs) known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR) proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169) exhibited antagonism to the five phytopathogens, of which 68% (50/73) of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169) of endophytes emitted host defense inducing VOCs (acetoin/diacetyl) and 62% (104/169) secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated cucurbits

  18. Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

    Directory of Open Access Journals (Sweden)

    Eman M. Khalaf

    2018-02-01

    Full Text Available The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanideratum. The endophytes were also assayed in planta (leaf disk and detached leaf bioassays for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169 exhibited antagonism to the five phytopathogens, of which 68% (50/73 of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169 of endophytes emitted host defense inducing VOCs (acetoin/diacetyl and 62% (104/169 secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated

  19. ANTAGONISM OF PROGESTERONE RECEPTOR SUPPRESSES CAROTID BODY RESPONSES TO HYPOXIA AND NICOTINE IN RAT PUPS

    OpenAIRE

    JOSEPH, V.; NIANE, L. M.; BAIRAM, A.

    2012-01-01

    We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between post-natal days 3 and 15. In 11–14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in...

  20. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

    DEFF Research Database (Denmark)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

    2013-01-01

    , and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

  1. An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor

    Science.gov (United States)

    Dagdas, Yasin F; Belhaj, Khaoula; Maqbool, Abbas; Chaparro-Garcia, Angela; Pandey, Pooja; Petre, Benjamin; Tabassum, Nadra; Cruz-Mireles, Neftaly; Hughes, Richard K; Sklenar, Jan; Win, Joe; Menke, Frank; Findlay, Kim; Banfield, Mark J; Kamoun, Sophien; Bozkurt, Tolga O

    2016-01-01

    Plants use autophagy to safeguard against infectious diseases. However, how plant pathogens interfere with autophagy-related processes is unknown. Here, we show that PexRD54, an effector from the Irish potato famine pathogen Phytophthora infestans, binds host autophagy protein ATG8CL to stimulate autophagosome formation. PexRD54 depletes the autophagy cargo receptor Joka2 out of ATG8CL complexes and interferes with Joka2's positive effect on pathogen defense. Thus, a plant pathogen effector has evolved to antagonize a host autophagy cargo receptor to counteract host defenses. DOI: http://dx.doi.org/10.7554/eLife.10856.001 PMID:26765567

  2. Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

    Directory of Open Access Journals (Sweden)

    Eman M. Khalaf

    2018-02-01

    Full Text Available The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanidermatum. The endophytes were also assayed in planta (leaf disk and detached leaf bioassays for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169 exhibited antagonism to the five phytopathogens, of which 68% (50/73 of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169 of endophytes emitted host defense inducing VOCs (acetoin/diacetyl and 62% (104/169 secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated

  3. Experimental testing of Mackay's model for functional antagonism in the isolated costo-uterus of the rat.

    Science.gov (United States)

    Henry, P. J.; Lulich, K. M.; Paterson, J. W.

    1985-01-01

    Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo-uterine preparation. In the presence of the functional antagonist fenoterol (Fen), the functional constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods. As predicted from the model of functional antagonism, the plot of KAF/KA-1 against the fraction of cholinoceptors not irreversibly blocked by phenoxybenzamine (Pbz) was linear for both carbachol and Oxo and the lines of best fit crossed the axes at a point not significantly different from the origin. The value of 4.6 for the relative efficacy of carbachol to Oxo estimated from functional antagonism studies was comparable to the value of 5.6 calculated using the method of irreversible antagonism proposed by Furchgott (1966). PMID:3840396

  4. Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome.

    Science.gov (United States)

    Rydzewski, W T; Carioscia, S A; Liévano, G; Lynch, V D; Patten, M M

    2016-06-01

    Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  5. Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular preparations from rats

    Directory of Open Access Journals (Sweden)

    C.R. Ambiel

    2001-04-01

    Full Text Available Nitric oxide (NO-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg at the presynaptic level increases the amplitude of muscular contraction (AMC and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle.

  6. IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

    Directory of Open Access Journals (Sweden)

    Jingyou Yu

    2015-10-01

    Full Text Available The interferon-induced transmembrane (IFITM proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env, thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

  7. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    International Nuclear Information System (INIS)

    Molenaar, P.; Malta, E.

    1986-01-01

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-[ 125 I]iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants

  8. Antagonism of Trichoderma harzianum ETS 323 on Botrytis cinerea mycelium in culture conditions.

    Science.gov (United States)

    Cheng, Chi-Hua; Yang, Chia-Ann; Peng, Kou-Cheng

    2012-11-01

    ABSTRACT Previous studies have shown that the extracellular proteins of Trichoderma harzianum ETS 323 grown in the presence of deactivated Botrytis cinerea in culture include a putative l-amino acid oxidase and have suggested the involvement of this enzyme in the antagonistic mechanism. Here, we hypothesized that the mycoparasitic process of Trichoderma spp. against B. cinerea involves two steps; that is, an initial hyphal coiling stage and a subsequent hyphal coiling stage, with different coiling rates. The two-step antagonism of T. harzianum ETS 323 against B. cinerea during the mycoparasitic process in culture was evaluated using a biexponential equation. In addition, an l-amino acid oxidase (Th-l-AAO) was identified from T. harzianum ETS 323. The secretion of Th-l-AAO was increased when T. harzianum ETS 323 was grown with deactivated hyphae of B. cinerea. Moreover, in vitro assays indicated that Th-l-AAO effectively inhibited B. cinerea hyphal growth, caused cytosolic vacuolization in the hyphae, and led to hyphal lysis. Th-l-AAO also showed disease control against the development of B. cinerea on postharvest apple fruit and tobacco leaves. Furthermore, an apoptosis-like response, including the generation of reactive oxygen species, was observed in B. cinerea after treatment with Th-l-AAO, suggesting that Th-l-AAO triggers programmed cell death in B. cinerea. This may be associated with the two-step antagonism of T. harzianum ETS 323 against B. cinerea.

  9. Effect of endothelin antagonism on apnea frequency following chronic intermittent hypoxia.

    Science.gov (United States)

    Donovan, Lucas M; Liu, Yuzhen; Weiss, J Woodrow

    2014-04-01

    Chronic hypoxia increases the hypoxic ventilatory response (HVR). Augmented HVR contributes to central apneas seen in heart failure and complex sleep apnea. Endothelin receptor (ETR) antagonism decreases carotid body afferent activity following chronic intermittent hypoxia (CIH). We speculated ETR antagonism would reduce HVR and apneas following CIH. HVR and apneas were measured after exposure to CIH and room air sham (SHAM). ETR blocker Ambrisentan was administered via the chow of CIH-exposed animals from days 1 to 12 of CIH (CIH/AMB). A separate crossover group was exposed to CIH and fed normal chow (placebo) days 1-6, and Ambrisentan days 7-12 (CIH/PLA-AMB). SHAM and CIH/PLA animals were fed placebo days 1-12. The CIH/AMB and CIH/PLA-AMB rats had reduced HVR compared to CIH/PLA, similar HVR compared to sham exposed animals, and reduced apnea frequency compared to CIH/PLA animals. The reduced HVR and post-hypoxic apneas resulting from Ambrisentan administration suggests ETR antagonists may have utility in reducing central apneas following CIH. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Dynamical transitions in a pollination-herbivory interaction: a conflict between mutualism and antagonism.

    Directory of Open Access Journals (Sweden)

    Tomás A Revilla

    Full Text Available Plant-pollinator associations are often seen as purely mutualistic, while in reality they can be more complex. Indeed they may also display a diverse array of antagonistic interactions, such as competition and victim-exploiter interactions. In some cases mutualistic and antagonistic interactions are carried-out by the same species but at different life-stages. As a consequence, population structure affects the balance of inter-specific associations, a topic that is receiving increased attention. In this paper, we developed a model that captures the basic features of the interaction between a flowering plant and an insect with a larval stage that feeds on the plant's vegetative tissues (e.g. leaves and an adult pollinator stage. Our model is able to display a rich set of dynamics, the most remarkable of which involves victim-exploiter oscillations that allow plants to attain abundances above their carrying capacities and the periodic alternation between states dominated by mutualism or antagonism. Our study indicates that changes in the insect's life cycle can modify the balance between mutualism and antagonism, causing important qualitative changes in the interaction dynamics. These changes in the life cycle could be caused by a variety of external drivers, such as temperature, plant nutrients, pesticides and changes in the diet of adult pollinators.

  11. Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1981-03-26

    Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.

  12. FCJ-156 Hacking the Social: Internet Memes, Identity Antagonism, and the Logic of Lulz.

    Directory of Open Access Journals (Sweden)

    Ryan M. Milner

    2013-12-01

    Full Text Available 4chan and reddit are participatory media collectives undergirded by a “logic of lulz” that favours distanced irony and critique. It often works at the expense of core identity categories like race and gender. However, the logic need not be entirely counterproductive to public discourse. Provided that diverse identities find voice instead of exclusion, these sites may facilitate vibrant, agonistic discussion instead of disenfranchising antagonism. In order to assess this potential for productive agonism, I undertook a critical discourse analysis of these collectives. Emphasising the image memes they produce, I evaluated discourses on race and gender. Both race and gender representations were dominated by familiar stereotypes and partial representations. However, while dissenting perspectives on race were repressed or excluded, dissenting perspectives on gender were vocalised and contested. The ‘logic of lulz’ facilitated both dominance and counter, each articulated with heavy reliance on irony and critique. This logic ambiguously balanced agonism and antagonism, but contestation provided sharper engagement than repression.

  13. Antagonism between abscisic acid and gibberellins is partially mediated by ascorbic acid during seed germination in rice.

    Science.gov (United States)

    Ye, Nenghui; Zhang, Jianhua

    2012-05-01

    The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. In the associated study, we investigated the relationship among ABA, reactive oxygen species (ROS), ascorbic acid (ASC) and GA during rice seed germination. ROS production is reduced by ABA, which hence results in decreasing ASC accumulation during imbibition. GA accumulation was also suppressed by a reduced ROS and ASC level, whereas application of exogenous ASC can partially rescue seed germination from ABA treatment. Further results show that production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. These studies reveal a new role for ASC in mediating the antagonism between ABA and GA during seed germination in rice.

  14. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    Science.gov (United States)

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  15. Aggression, Sibling Antagonism, and Theory-of-Mind During the First Year of Siblinghood: A Developmental Cascade Model

    Science.gov (United States)

    Song, Ju-Hyun; Volling, Brenda L.; Lane, Jonathan D.; Wellman, Henry M.

    2016-01-01

    A developmental cascade model was tested to examine longitudinal associations among firstborn children’s aggression, Theory-of-Mind, and antagonism toward their younger sibling during the first year of siblinghood. Aggression and Theory-of-Mind were assessed before the birth of a sibling, and 4 and 12 months after the birth, and antagonism was examined at 4 and 12 months in a sample of 208 firstborn children (initial M age = 30 months, 56% girls) from primarily European American, middle- class families. Firstborns’ aggression consistently predicted high sibling antagonism both directly and through poorer Theory-of-Mind. Results highlight the importance of examining longitudinal influences across behavioral, social-cognitive, and relational factors that are closely intertwined even from the early years of life. PMID:27096923

  16. Symbiont interactions in a tripartite mutualism: exploring the presence and impact of antagonism between two fungus-growing ant mutualists.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Mutualistic associations are shaped by the interplay of cooperation and conflict among the partners involved, and it is becoming increasingly clear that within many mutualisms multiple partners simultaneously engage in beneficial interactions. Consequently, a more complete understanding of the dynamics within multipartite mutualism communities is essential for understanding the origin, specificity, and stability of mutualisms. Fungus-growing ants cultivate fungi for food and maintain antibiotic-producing Pseudonocardia actinobacteria on their cuticle that help defend the cultivar fungus from specialized parasites. Within both ant-fungus and ant-bacterium mutualisms, mixing of genetically distinct strains can lead to antagonistic interactions (i.e., competitive conflict, which may prevent the ants from rearing multiple strains of either of the mutualistic symbionts within individual colonies. The success of different ant-cultivar-bacterium combinations could ultimately be governed by antagonistic interactions between the two mutualists, either as inhibition of the cultivar by Pseudonocardia or vice versa. Here we explore cultivar-Pseudonocardia antagonism by evaluating in vitro interactions between strains of the two mutualists, and find frequent antagonistic interactions both from cultivars towards Pseudonocardia and vice versa. To test whether such in vitro antagonistic interactions affect ant colonies in vivo, we performed sub-colony experiments using species of Acromyrmex leaf-cutting ants. We created novel ant-fungus-bacterium pairings in which there was antagonism from one, both, or neither of the ants' microbial mutualists, and evaluated the effect of directional antagonism on cultivar biomass and Pseudonocardia abundance on the cuticle of workers within sub-colonies. Despite the presence of frequent in vitro growth suppression between cultivars and Pseudonocardia, antagonism from Pseudonocardia towards the cultivar did not reduce sub

  17. Inhibition of protein synthesis does not antagonize induction of UV-induced sister-chromatid exchange in xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Sono, Akira; Sakaguchi, Kengo.

    1988-01-01

    Cycloheximide strongly antagonizes the induction of sisterchromatid exchanges by ethyl methanesulfonate or mitomycin C in human skin fibroblast and xeroderma pigmentosum cells (group A). Analogous behavior has been observed in several other species including Chinese hamster and plant cells. This report documents an exception to that pattern: cycloheximide fails to antagonize UV-induced sister chromatid exchange in xeroderma pigmentosum cells, whereas it does in normal human skin fibroblast cells. A genetic defect in these cells is postulated to alter the UV-mediated DNA recombination process. (author)

  18. Nitrogen loss in Brachiaria decumbens after application of glyphosate or glufosinate-ammonium Perdas de nitrogênio por Brachiaria decumbens após a aplicação de glifosato ou glufosinato de amônio

    Directory of Open Access Journals (Sweden)

    Virginia Damin

    2008-01-01

    Full Text Available Nitrogen losses from the soil-plant system may be influenced by herbicide applications. In order to evaluate N loss in brachiaria (Brachiaria decumbens after application of the herbicides glyphosate and glufosinate-ammonium, an experiment was carried out in a greenhouse as a completely randomized design, with three treatments and six replicates. Treatments were as follows: i desiccation of brachiaria-plants with glyphosate; ii desiccation of brachiaria-plants with glufosinate-ammonium; and iii control, without herbicide application. The plants were cultivated in 4 kg pots of sandy soil and fertilized with ammonium sulfate- 15N, (200 mg kg-1 in order to quantify the allocation of the fertilizer-N and its recovery in the soil-plant system. Plants treated with the herbicides had less N accumulation and less recovery of the fertilizer-N (15N relative to the control. In the soil, the greatest recovery of 15N-fertilizer occurred for treatments where N was applied, possibly due to the occurrence of other N compound losses to the soil, like root exudation and root death. The total recovery of 15N-fertilizer in the soil-plant system was higher in the control than in the treated plants showing the direct action of the herbicides on nitrogen loss, and especially by the above-ground part of the brachiaria plants.As perdas de nitrogênio no sistema solo-planta podem ser influenciadas pela aplicação de herbicidas. Com o objetivo de avaliar a perda de N do capim-Brachiaria (Brachiaria decumbens após a aplicação dos herbicidas glifosato e glufosinato de amônio, foi realizado um experimento em casa-de-vegetação em delineamento inteiramente aleatorizado (DIA, com três tratamentos e seis repetições. Os tratamentos foram os seguintes: i dessecação de plantas de braquiária com o herbicida glifosato; ii dessecação de plantas de braquiária com herbicida glufosinato de amônio e iii testemunha, sem aplicação de herbicida. As plantas foram cultivadas

  19. Disruption of Cell-to-Cell Signaling Does Not Abolish the Antagonism of Phaeobacter gallaeciensis toward the Fish Pathogen Vibrio anguillarum in Algal Systems

    DEFF Research Database (Denmark)

    Prol García, María Jesús; D'Alvise, Paul; Gram, Lone

    2013-01-01

    Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobac...... Phaeobacter and QS inhibitors is a feasible strategy for aquaculture disease control....

  20. CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

    Science.gov (United States)

    Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

    2006-10-01

    Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

  1. Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats

    DEFF Research Database (Denmark)

    Clausen, Bettina; Schachtman, Todd R.; Mark, Louise T.

    2011-01-01

    to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non......-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting......D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390...

  2. GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations

    DEFF Research Database (Denmark)

    Deacon, Carolyn F; Plamboeck, Astrid; Rosenkilde, Mette M

    2006-01-01

    Glucose-dependent insulinotropic polypeptide [GIP-(1-42)] is degraded by dipeptidyl peptidase IV (DPP IV), forming GIP-(3-42). In mice, high concentrations of synthetic GIP-(3-42) may function as a GIP receptor antagonist, but it is unclear whether this occurs at physiological concentrations...... GIP, GIP-(3-42) behaved as a weak antagonist (IC(50), 92 and 731 nM for inhibition of cAMP accumulation elicited by 10 pM and 1 nM native GIP, respectively). In the isolated perfused rat pancreas, GIP-(3-42) alone had no effect on insulin output and only reduced the response to GIP (1 nM) when......-42) can weakly antagonize cAMP accumulation and insulin output in vitro, it does not behave as a physiological antagonist in vivo....

  3. USP10 Antagonizes c-Myc Transcriptional Activation through SIRT6 Stabilization to Suppress Tumor Formation

    Directory of Open Access Journals (Sweden)

    Zhenghong Lin

    2013-12-01

    Full Text Available The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

  4. Isolation of Fungi from Heterodera glycines and in vitro Bioassays for Their Antagonism to Eggs.

    Science.gov (United States)

    Meyer, S L; Huettel, R N; Sayre, R M

    1990-10-01

    Twenty fungi were assayed in vitro for antagonism to eggs of Heterodera glycines. Eight of the fungi were isolated from cysts or eggs of H. glycines during the current study, one was isolated from Panagrellus redivivus, and eleven were obtained from other researchers or collections. The bioassays were conducted on eggs from nematodes that had been grown monoxenically on excised root tips. Phoma chrysanthemicola, one strain of Verticillium chlamydosporium, and one strain of V. lecanii caused a decrease (P Trichoderma polysporum infected live eggs but enhanced (P Fusarium sp., Neocosmospora vasinfecta, Scytalidium fulvum, Trichoderma harzianum (two strains), V. chlamydosporium (one strain), V. lecanii (three strains), and an unidentified fungus did not measurably affect egg viability, even though hyphae of five of these fungi were seen in live eggs. The bioassay provides a useful step in the selection of a biological control agent for this major nematode pest.

  5. Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Jensen, Morten; Weikop, Pia

    2012-01-01

    Rationale Several studies suggest a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. However, the NPY receptors mediating addiction-related effects remain to be determined. Objectives To explore the potential role of Y5 NPY receptors in cocaine-induced behavioural...... effects. Methods The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in two models of cocaine addiction-related behaviour: acute self-administration and cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism on cocaine-induced c-fos expression and extracellular...... effects, suggesting that Y5 receptors could be a potential therapeutic target in cocaine addiction....

  6. Combining climate and energy policies: synergies or antagonism? Modeling interactions with energy efficiency instruments

    International Nuclear Information System (INIS)

    Lecuyer, Oskar; Bibas, Ruben

    2012-01-01

    In addition to the already present Climate and Energy package, the European Union (EU) plans to include a binding target to reduce energy consumption. We analyze the rationales the EU invokes to justify such an overlapping and develop a minimal common framework to study interactions arising from the combination of instruments reducing emissions, promoting renewable energy (RE) production and reducing energy demand through energy efficiency (EE) investments. We find that although all instruments tend to reduce GHG emissions and although a price on carbon tends also to give the right incentives for RE and EE, the combination of more than one instrument leads to significant antagonisms regarding major objectives of the policy package. The model allows to show in a single framework and to quantify the antagonistic effects of the joint promotion of RE and EE. We also show and quantify the effects of this joint promotion on ETS permit price, on wholesale market price and on energy production levels. (authors)

  7. What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?

    Energy Technology Data Exchange (ETDEWEB)

    Kufareva, Irina; Gustavsson, Martin; Zheng, Yi; Stephens, Bryan S.; Handel, Tracy M. (UCSD)

    2017-05-22

    Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novel epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.

  8. An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.

    Science.gov (United States)

    Rockwell, W B; Ehrlich, H P

    1991-02-01

    Serum-free culture medium harvested from endothelial cell monolayer cultures derived from human scars and dermis was examined for inhibition of fibrinolysis using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells did not produce any detectable inhibitory activity. The inhibitor is spontaneously released from the cultured endothelial cells over time. In the fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin and tolmetin have minimal antagonistic activity. Heating the cultured endothelial cells to 42 degrees C stimulates greater release of the inhibitor in a shorter period of time. This plasmin inhibitor, which is produced by endothelial cells, may contribute to postburn vascular occlusion, leading to secondary progressive necrosis in burn-traumatized patients.

  9. Silencing the alarms: innate immune antagonism by rotavirus NSP1 and VP3

    Science.gov (United States)

    Morelli, Marco; Ogden, Kristen M.; Patton, John T.

    2016-01-01

    The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFN) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)-RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other RV species evade host innate immune responses. PMID:25724417

  10. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset

    DEFF Research Database (Denmark)

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang

    2016-01-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured...

  11. Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N

    2013-01-01

    The Epstein-Barr virus induced gene 2 (EBI2) was recently identified as the first oxysterol-activated 7TM receptor. EBI2 is essential for B cell trafficking within lymphoid tissues and thus the humoral immune response in general. Here we characterize the antagonism of the non-peptide molecule GSK...

  12. Comparison of vascular alpha(1)-adrenoceptor antagonism of tamsulosin in oral controlled absorption system (OCAS) and modified release (MR) formulations

    NARCIS (Netherlands)

    Michel, M. C.; Korstanje, C.; Krauwinkel, W.; Shear, M.; Davies, J.; Quartel, A.

    2005-01-01

    Objective: The cardiovascular a-l-adrenoceptor (AR) antagonism of the new oral controlled absorption system (OCAS) 0.4 mg tablet formulation of tamsulosin was compared with that of the modified release (MR) 0.4 mg capsule formulation in healthy male volunteers after a single dose in the fasted

  13. Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2.

    Science.gov (United States)

    Toth, Krisztian; Slosky, Lauren M; Pack, Thomas F; Urs, Nikhil M; Boone, Peter; Mao, Lan; Abraham, Dennis; Caron, Marc G; Barak, Lawrence S

    2018-01-01

    The "brain-gut" peptide ghrelin, which mediates food-seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein-coupled receptor GHSR1a, and administration of ghrelin increases the rewarding properties of psychostimulants while ghrelin receptor antagonists decrease them. In addition, the GHSR1a signals through βarrestin-2 to regulate actin/stress fiber rearrangement, suggesting βarrestin-2 participation in the regulation of actin-mediated synaptic plasticity for addictive substances like cocaine. The effects of ghrelin receptor ligands on reward strongly suggest that modulation of ghrelin signaling could provide an effective strategy to ameliorate undesirable behaviors arising from addiction. To investigate this possibility, we tested the effects of ghrelin receptor antagonism in a cocaine behavioral sensitization paradigm using DA neuron-specific βarrestin-2 KO mice. Our results show that these mice sensitize to cocaine as well as wild-type littermates. The βarrestin-2 KO mice, however, no longer respond to the locomotor attenuating effects of the GHSR1a antagonist YIL781. The data presented here suggest that the separate stages of addictive behavior differ in their requirements for βarrestin-2 and show that pharmacological inhibition of βarrestin-2 function through GHSR1a antagonism is not equivalent to the loss of βarrestin-2 function achieved by genetic ablation. These data support targeting GHSR1a signaling in addiction therapy but indicate that using signaling biased compounds that modulate βarrestin-2 activity differentially from G protein activity may be required. © 2017 Wiley Periodicals, Inc.

  14. Comparative analyses of reproductive structures in harvestmen (opiliones reveal multiple transitions from courtship to precopulatory antagonism.

    Directory of Open Access Journals (Sweden)

    Mercedes M Burns

    Full Text Available Explaining the rapid, species-specific diversification of reproductive structures and behaviors is a long-standing goal of evolutionary biology, with recent research tending to attribute reproductive phenotypes to the evolutionary mechanisms of female mate choice or intersexual conflict. Progress in understanding these and other possible mechanisms depends, in part, on reconstructing the direction, frequency and relative timing of phenotypic evolution of male and female structures in species-rich clades. Here we examine evolution of reproductive structures in the leiobunine harvestmen or "daddy long-legs" of eastern North America, a monophyletic group that includes species in which males court females using nuptial gifts and other species that are equipped for apparent precopulatory antagonism (i.e., males with long, hardened penes and females with sclerotized pregenital barriers. We used parsimony- and Bayesian likelihood-based analyses to reconstruct character evolution in categorical reproductive traits and found that losses of ancestral gift-bearing penile sacs are strongly associated with gains of female pregenital barriers. In most cases, both events occur on the same internal branch of the phylogeny. These coevolutionary changes occurred at least four times, resulting in clade-specific designs in the penis and pregenital barrier. The discovery of convergent origins and/or enhancements of apparent precopulatory antagonism among closely related species offers an unusual opportunity to investigate how major changes in reproductive morphology have occurred. We propose new hypotheses that attribute these enhancements to changes in ecology or life history that reduce the duration of breeding seasons, an association that is consistent with female choice, sexual conflict, and/or an alternative evolutionary mechanism.

  15. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A.

    Directory of Open Access Journals (Sweden)

    Chelsi D Cassilly

    Full Text Available In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS synthase (Cho1p was developed based on antagonism of the toxin papuamide A (Pap-A. Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A, but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins.

  16. Vascular permeabilization by intravenous arachidonate in the rat peritoneal cavity: antagonism by ethamsylate.

    Science.gov (United States)

    Hannaert, Patrick; Alvarez-Guerra, Miriam; Hider, Hamida; Chiavaroli, Carlo; Garay, Ricardo P

    2003-04-11

    The hemostatic agent, ethamsylate, inhibits arachidonic acid metabolism by a mechanism independent of cyclooxygenase activity and blocks carrageenan-induced rat paw edema. Here, ethamsylate was investigated for (i) in vivo actions on the free radical-dependent, permeabilizing responses to arachidonic acid and (ii) its antioxidant potential in vitro. Vascular permeability was equated to the extravasation rate of Evans blue from plasma into the rat peritoneal cavity. Antioxidant potential was investigated by classical in vitro tests for superoxide radicals, hydroxyl radicals (OH(.)), and nitric oxide. Intravenous ethamsylate induced a very important and significant reduction of permeability responses to arachidonate, both when given preventively and cumulatively. Thus, (i) ethamsylate significantly reversed arachidonate-induced permeabilization, even at the lowest dose tested (44+/-5% at 10 mg/kg) and (ii) a maximal reversal (about 70%) was reached between 50 and 200 mg/kg ethamsylate. In contrast, ethamsylate (100 mg/kg) was unable to antagonize the vascular permeabilization induced by serotonin (5-HT). In antioxidant assays, ethamsylate showed scavenging properties against hydroxyl radicals generated by the Fenton reaction (H(2)O(2)/Fe(2+)) even at 0.1 microM (-20+/-3%). OH(.) scavenging by ethamsylate reached 42+/-8% at 10 microM and 57+/-7% at 1 mM and was comparable to that of reference compounds (vitamin E, troxerutin, and mannitol). Conversely, ethamsylate was a poor scavenger of superoxide and nitric oxide radicals. In conclusion, intravenous ethamsylate potently antagonized the peritoneal vascular permeabilization induced by arachidonate, an action likely due to its antioxidant properties, particularly against hydroxyl radical. Such a mechanism can explain previous observations that ethamsylate inhibits carrageenan-induced rat paw edema. Whether it also participates in the hemostatic action of ethamsylate deserves further investigation.

  17. Environmental variation shifts the relationship between trees and scatterhoarders along the continuum from mutualism to antagonism.

    Science.gov (United States)

    Sawaya, Gina M; Goldberg, Adam S; Steele, Michael A; Dalgleish, Harmony J

    2018-05-01

    The conditional mutualism between scatterhoarders and trees varies on a continuum from mutualism to antagonism and can change across time and space, and among species. We examined 4 tree species (red oak [Quercus rubra], white oak [Quercus alba], American chestnut [Castanea dentata] and hybrid chestnut [C. dentata × Castanea mollissima) across 5 sites and 3 years to quantify the variability in this conditional mutualism. We used a published model to compare the rates of seed emergence with and without burial to the probability that seeds will be cached and left uneaten by scatterhoarders to quantify variation in the conditional mutualism that can be explained by environmental variation among sites, years, species, and seed provenance within species. All species tested had increased emergence when buried. However, comparing benefits of burial to the probability of caching by scatterhoarders indicated a mutualism in red oak, while white oak was nearly always antagonistic. Chestnut was variable around the boundary between mutualism and antagonism, indicating a high degree of context dependence in the relationship with scatterhoarders. We found that different seed provenances did not vary in their potential for mutualism. Temperature did not explain microsite differences in seed emergence in any of the species tested. In hybrid chestnut only, emergence on the surface declined with soil moisture in the fall. By quantifying the variation in the conditional mutualism that was not caused by changes in scatterhoarder behavior, we show that environmental conditions and seed traits are an important and underappreciated component of the variation in the relationship between trees and scatterhoarders. © 2018 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  18. The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole.

    Science.gov (United States)

    Christina Haerdi-Landerer, M; Schlegel, Urs; Neiger-Aeschbacher, Gina

    2005-09-01

    To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). Prospective, randomized, cross-over. Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.

  19. Antagonism pattern detection between microRNA and target expression in Ewing's sarcoma.

    Directory of Open Access Journals (Sweden)

    Loredana Martignetti

    Full Text Available MicroRNAs (miRNAs have emerged as fundamental regulators that silence gene expression at the post-transcriptional and translational levels. The identification of their targets is a major challenge to elucidate the regulated biological processes. The overall effect of miRNA is reflected on target mRNA expression, suggesting the design of new investigative methods based on high-throughput experimental data such as miRNA and transcriptome profiles. We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, in order to infer miRNA-target interactions. This approach, which we name antagonism pattern detection, is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data. The procedure has been assessed on synthetic datasets and tested on a set of real positive controls. Then it has been applied to analyze expression data from Ewing's sarcoma patients. The antagonism relationship is evaluated as a good indicator of real miRNA-target biological interaction. The predicted targets are consistently enriched for miRNA binding site motifs in their 3'UTR. Moreover, we reveal sets of predicted targets for each miRNA sharing important biological function. The procedure allows us to infer crucial miRNA regulators and their potential targets in Ewing's sarcoma disease. It can be considered as a valid statistical approach to discover new insights in the miRNA regulatory mechanisms.

  20. Differential effects of early-life NMDA receptor antagonism on aspartame-impaired insulin tolerance and behavior.

    Science.gov (United States)

    Collison, Kate S; Inglis, Angela; Shibin, Sherin; Andres, Bernard; Ubungen, Rosario; Thiam, Jennifer; Mata, Princess; Al-Mohanna, Futwan A

    2016-12-01

    We have previously showed that lifetime exposure to aspartame, commencing in utero via the mother's diet, may impair insulin tolerance and cause behavioral deficits in adulthood via mechanisms which are incompletely understood. The role of the CNS in regulating glucose homeostasis has been highlighted by recent delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors (NMDARs) are important in maintaining glucose homeostasis, in addition to regulating certain aspects of behavior. Since the gut-brain axis can be modulated by fetal programming, we hypothesized that early-life NMDAR antagonism may affect aspartame-induced glucose deregulation in adulthood, and may alter the aspartame behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to aspartame commencing in utero, in the presence and absence of maternal administration of the competitive NMDAR antagonist CGP 39551, from conception until weaning. Drug/diet interactions in adulthood glucocentric and behavioral parameters were assessed. Aspartame exposure elevated blood glucose and impaired insulin-induced glucose disposal during an insulin tolerance test, which could be normalized by NMDAR antagonism. The same effects were not observed in control diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of adult offspring indicated that NMDAR antagonism of control diet mice caused hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, reduced exploratory activity and increased anxiety-related behavior were apparent in aspartame diet mice with early-life NMDAR antagonism. significant drug/diet interactions in glucocentric and behavioral parameters were identified in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a possible involvement of early NMDAR interactions in aspartame-impaired glucose homeostasis and behavioral deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The parental antagonism theory of language evolution: preliminary evidence for the proposal.

    Science.gov (United States)

    Brown, William M

    2011-04-01

    not maternally silenced Alu elements are positively correlated with language diversity. Furthermore, there is a much higher than expected frequency of Alu elements inserted into the protein-coding machinery of imprinted and X-chromosomal language loci compared with nonimprinted language loci. Taken together these findings provide some support for parental antagonism theory. Unlike previous theories for language evolution, parental antagonism theory generates testable predictions at the proximate (e.g., neurocognitive areas important for social transmission and language capacities), ontogenetic (e.g., the function of language at different points of development), ultimate (e.g., inclusive fitness), and phylogenetic levels (e.g., the spread of maternally derived brain components in mammals, particularly in the hominin lineage), thus making human capacities for culture more tractable than previously thought.

  2. Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.

    Science.gov (United States)

    Morrison, James H; Guevara, Rebekah B; Marcano, Adriana C; Saenz, Dyana T; Fadel, Hind J; Rogstad, Daniel K; Poeschla, Eric M

    2014-03-01

    BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is

  3. Brassinosteroids Antagonize Gibberellin- and Salicylate-Mediated Root Immunity in Rice1[C][W][OA

    Science.gov (United States)

    De Vleesschauwer, David; Van Buyten, Evelien; Satoh, Kouji; Balidion, Johny; Mauleon, Ramil; Choi, Il-Ryong; Vera-Cruz, Casiana; Kikuchi, Shoshi; Höfte, Monica

    2012-01-01

    Brassinosteroids (BRs) are a unique class of plant steroid hormones that orchestrate myriad growth and developmental processes. Although BRs have long been known to protect plants from a suite of biotic and abiotic stresses, our understanding of the underlying molecular mechanisms is still rudimentary. Aiming to further decipher the molecular logic of BR-modulated immunity, we have examined the dynamics and impact of BRs during infection of rice (Oryza sativa) with the root oomycete Pythium graminicola. Challenging the prevailing view that BRs positively regulate plant innate immunity, we show that P. graminicola exploits BRs as virulence factors and hijacks the rice BR machinery to inflict disease. Moreover, we demonstrate that this immune-suppressive effect of BRs is due, at least in part, to negative cross talk with salicylic acid (SA) and gibberellic acid (GA) pathways. BR-mediated suppression of SA defenses occurred downstream of SA biosynthesis, but upstream of the master defense regulators NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and OsWRKY45. In contrast, BR alleviated GA-directed immune responses by interfering at multiple levels with GA metabolism, resulting in indirect stabilization of the DELLA protein and central GA repressor SLENDER RICE1 (SLR1). Collectively, these data favor a model whereby P. graminicola coopts the plant BR pathway as a decoy to antagonize effectual SA- and GA-mediated defenses. Our results highlight the importance of BRs in modulating plant immunity and uncover pathogen-mediated manipulation of plant steroid homeostasis as a core virulence strategy. PMID:22353574

  4. Brassinosteroids antagonize gibberellin- and salicylate-mediated root immunity in rice.

    Science.gov (United States)

    De Vleesschauwer, David; Van Buyten, Evelien; Satoh, Kouji; Balidion, Johny; Mauleon, Ramil; Choi, Il-Ryong; Vera-Cruz, Casiana; Kikuchi, Shoshi; Höfte, Monica

    2012-04-01

    Brassinosteroids (BRs) are a unique class of plant steroid hormones that orchestrate myriad growth and developmental processes. Although BRs have long been known to protect plants from a suite of biotic and abiotic stresses, our understanding of the underlying molecular mechanisms is still rudimentary. Aiming to further decipher the molecular logic of BR-modulated immunity, we have examined the dynamics and impact of BRs during infection of rice (Oryza sativa) with the root oomycete Pythium graminicola. Challenging the prevailing view that BRs positively regulate plant innate immunity, we show that P. graminicola exploits BRs as virulence factors and hijacks the rice BR machinery to inflict disease. Moreover, we demonstrate that this immune-suppressive effect of BRs is due, at least in part, to negative cross talk with salicylic acid (SA) and gibberellic acid (GA) pathways. BR-mediated suppression of SA defenses occurred downstream of SA biosynthesis, but upstream of the master defense regulators NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and OsWRKY45. In contrast, BR alleviated GA-directed immune responses by interfering at multiple levels with GA metabolism, resulting in indirect stabilization of the DELLA protein and central GA repressor SLENDER RICE1 (SLR1). Collectively, these data favor a model whereby P. graminicola coopts the plant BR pathway as a decoy to antagonize effectual SA- and GA-mediated defenses. Our results highlight the importance of BRs in modulating plant immunity and uncover pathogen-mediated manipulation of plant steroid homeostasis as a core virulence strategy.

  5. Abscisic Acid-Cytokinin Antagonism Modulates Resistance Against Pseudomonas syringae in Tobacco.

    Science.gov (United States)

    Großkinsky, Dominik K; van der Graaff, Eric; Roitsch, Thomas

    2014-12-01

    Phytohormones are known as essential regulators of plant defenses, with ethylene, jasmonic acid, and salicylic acid as the central immunity backbone, while other phytohormones have been demonstrated to interact with this. Only recently, a function of the classic phytohormone cytokinin in plant immunity has been described in Arabidopsis, rice, and tobacco. Although interactions of cytokinins with salicylic acid and auxin have been indicated, the complete network of cytokinin interactions with other immunity-relevant phytohormones is not yet understood. Therefore, we studied the interaction of kinetin and abscisic acid as a negative regulator of plant immunity to modulate resistance in tobacco against Pseudomonas syringae. By analyzing infection symptoms, pathogen proliferation, and accumulation of the phytoalexin scopoletin as a key mediator of kinetin-induced resistance in tobacco, antagonistic interaction of these phytohormones in plant immunity was identified. Kinetin reduced abscisic acid levels in tobacco, while increased abscisic acid levels by exogenous application or inhibition of abscisic acid catabolism by diniconazole neutralized kinetin-induced resistance. Based on these results, we conclude that reduction of abscisic acid levels by enhanced abscisic acid catabolism strongly contributes to cytokinin-mediated resistance effects. Thus, the identified cytokinin-abscisic acid antagonism is a novel regulatory mechanism in plant immunity.

  6. Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice

    Science.gov (United States)

    Meguro, Ayano; Sato, Yutaka

    2014-04-01

    We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

  7. Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

    Science.gov (United States)

    Machta, Benjamin B.; Gray, Ellyn; Nouri, Mariam; McCarthy, Nicola L. C.; Gray, Erin M.; Miller, Ann L.; Brooks, Nicholas J.; Veatch, Sarah L.

    2016-08-01

    Diverse molecules induce general anesthesia with potency strongly correlated both with their hydrophobicity and their effects on certain ion channels. We recently observed that several n-alcohol anesthetics inhibit heterogeneity in plasma membrane derived vesicles by lowering the critical temperature ($T_c$) for phase separation. Here we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n-alcohols and effects on $T_c$. First we show that hexadecanol acts oppositely to n-alcohol anesthetics on membrane mixing and antagonizes ethanol induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described `intoxication reversers' raise $T_c$ and counter ethanol's effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that hydrostatic pressure, long known to reverse anesthesia, also raises $T_c$ in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that $\\Delta T_c$ predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia.

  8. TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected with Plasmodium berghei ANKA

    Directory of Open Access Journals (Sweden)

    Elizabeth S. Fernandes

    2014-01-01

    Full Text Available Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host’s defence to malaria. Transient receptor potential vanilloid 1 (TRPV1 modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 105 red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80+Ly6G+ cell numbers as well as activation of both F4/80+and F4/80+Ly6G+ cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1+ and natural killer (NK population, without interfering with natural killer T (NKT cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

  9. A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels

    Directory of Open Access Journals (Sweden)

    Cerrone Cabanos

    2017-08-01

    Full Text Available Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidic acid (PA has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K+-channel (TREK-1. Anionic lipids PA and phosphatidylglycerol (PG bind dose dependently (9.1 and 96 μM, respectively and agonize the channel. Our assay shows PIP2 binds with high affinity (0.87 μM but surprisingly can directly antagonize TREK-1 in liposomes. We propose a model for TREK-1 lipid regulation where PIP2 can compete with PA and PG agonism based on the affinity of the lipid for a site within the channel.

  10. Equilibrium switching and mathematical properties of nonlinear interaction networks with concurrent antagonism and self-stimulation

    International Nuclear Information System (INIS)

    Rabajante, Jomar Fajardo; Talaue, Cherryl Ortega

    2015-01-01

    Graphical abstract: Display Omitted -- Highlights: •Properties of n-dimensional decision model of competitive interaction networks. •Graphical technique for component-wise and steady state stability analysis. •Search for parameter conditions that control equilibrium switching. •Illustrations of multi-stable systems and repressilators. -- Abstract: Concurrent decision-making model (CDM) of interaction networks with more than two antagonistic components represents various biological systems, such as gene interaction, species competition and mental cognition. The CDM model assumes sigmoid kinetics where every component stimulates itself but concurrently represses the others. Here we prove generic mathematical properties (e.g., location and stability of steady states) of n-dimensional CDM with either symmetric or asymmetric reciprocal antagonism between components. Significant modifications in parameter values serve as biological regulators for inducing steady state switching by driving a temporal state to escape an undesirable equilibrium. Increasing the maximal growth rate and decreasing the decay rate can expand the basin of attraction of a steady state that contains the desired dominant component. Perpetually adding an external stimulus could shut down multi-stability of the system which increases the robustness of the system against stochastic noise. We further show that asymmetric interaction forming a repressilator-type network generates oscillatory behavior

  11. Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae)

    Science.gov (United States)

    Faraone, Nicoletta; Hillier, N. Kirk; Cutler, G. Christopher

    2015-01-01

    Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender) and Thymus vulgaris (thyme) and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur. PMID:26010088

  12. Biological activity of the non-microbial fraction of kefir: antagonism against intestinal pathogens.

    Science.gov (United States)

    Iraporda, Carolina; Abatemarco Júnior, Mário; Neumann, Elisabeth; Nunes, Álvaro Cantini; Nicoli, Jacques R; Abraham, Analía G; Garrote, Graciela L

    2017-08-01

    Kefir is a fermented milk obtained by the activity of kefir grains which are composed of lactic and acetic acid bacteria, and yeasts. Many beneficial health effects have been associated with kefir consumption such as stimulation of the immune system and inhibition of pathogenic microorganisms. The biological activity of kefir may be attributed to the presence of a complex microbiota as well as the microbial metabolites that are released during fermentation. The aim of this work was to characterise the non-microbial fraction of kefir and to study its antagonism against Escherichia coli, Salmonella spp. and Bacillus cereus. During milk fermentation there was a production of organic acids, mainly lactic and acetic acid, with a consequent decrease in pH and lactose content. The non-microbial fraction of kefir added to nutrient broth at concentrations above 75% v/v induced a complete inhibition of pathogenic growth that could be ascribed to the presence of un-dissociated lactic acid. In vitro assays using an intestinal epithelial cell model indicated that pre-incubation of cells with the non-microbial fraction of kefir did not modify the association/invasion of Salmonella whereas pre-incubation of Salmonella with this fraction under conditions that did not affect their viability significantly decreased the pathogen's ability to invade epithelial cells. Lactate exerted a protective effect against Salmonella in a mouse model, demonstrating the relevance of metabolites present in the non-microbial fraction of kefir produced during milk fermentation.

  13. Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice.

    Science.gov (United States)

    Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

    2017-02-01

    High intake of dietary fructose causes perturbation in lipid metabolism and provokes lipid-induced insulin resistance. A rise in glucocorticoids (GCs) has recently been suggested to be involved in fructose-induced insulin resistance. The objective of the study was to investigate the effect of GC blockade on lipid abnormalities in insulin-resistant mice. Insulin resistance was induced in mice by administering a high-fructose diet (HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC levels, the glucocorticoid receptor (GR) activation and the expression of GC-regulated genes involved in lipid metabolism were examined. HFrD elevated the intracellular GC content in both liver and adipose tissue and enhanced the GR nuclear translocation. The plasma GC level remained unchanged. The levels of free fatty acids and triglycerides in plasma were elevated, accompanied by increased plasma insulin and glucose levels and decreased hepatic glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC levels and the expression of GC-targeted genes involved in lipid accumulation, and it improved insulin sensitivity. This study demonstrated that HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced GC in liver and adipose tissue and that GC antagonism might reduce fructose-induced lipid abnormalities and insulin resistance. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  14. Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.

    Science.gov (United States)

    Riga, S; Riga, D; Schneider, F

    2004-06-01

    Distress and senescence, their reciprocal aggravating-quickening connections, and their related pathologies have a large worldwide impact on healthcare systems in this new millennium. For this reason, Antagonic-Stress (AS)--an advanced integrative therapy, with specific synergistic composition, and patented internationally--represents a significant strategy in health, aging, and longevity. Clinical research with AS proves the drug's efficacy in the management of distress (neurotic, stress-related, and affective disorders; behavioral syndromes associated with physiological disturbances and physical factors; mental and behavioral disorders due to psychoactive substance uses) and psychogeriatrics [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial psychopathological instruments and psychometric tests in multiple assessments used for gerontopsychiatry demonstrated strong improvements after AS administration in early-moderate stages of Alzheimer or vascular dementia, as well as in other OMD. In addition, comparative clinical studies evinced the superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These comparative clinical trials agreed closely with comparative preclinical research and confirmed AS synergistic homeostatic, adaptogenic, antioxidative, cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective actions against oxidative stress recommend this orthomolecular therapy in stress, aging, and free radical pathology.

  15. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, Jennifer L. [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Diamond, Michael S., E-mail: diamond@borcim.wustl.edu [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 (United States); Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110 (United States); The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110 (United States)

    2015-05-15

    N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.

  16. Endocannabinoid antagonism: blocking the excess in the treatment of high-risk abdominal obesity.

    Science.gov (United States)

    Duffy, Danielle; Rader, Daniel

    2007-02-01

    Abdominal obesity is a prevalent, worldwide problem linked to cardiometabolic comorbidities and an increased risk of coronary heart disease. First-line therapy to reduce such risk revolves around diet and exercise; however, such changes are often difficult to implement and unsuccessful. Understanding the underlying pathophysiology of underlying metabolic derangements could provide new targets for pharmacologic therapy. One system that has gained recent attention is the endocannabinoid system. The endocannabinoid system has a significant role in central appetite control and peripheral lipogenesis and is up-regulated in diet-induced obesity. Rimonabant is a selective cannabinoid-1 receptor antagonist and is the first compound of its type to test the hypothesis that down-regulating an overactive endocannabinoid system could have therapeutic benefit not only for weight loss but also for the atherogenic dyslipidemia and insulin resistance that cluster with abdominal obesity in particular. Animal models have been critical for elucidating the role of the endocannabinoid system in obesity and in demonstrating that antagonism with rimonabant can induce loss of visceral fat and improve insulin sensitivity. Early human trials with rimonabant have confirmed significant reductions in weight, as well as favorable changes in atherogenic dyslipidemia, insulin resistance, and markers of inflammation. Interestingly, some of these beneficial metabolic effects are partially weight-loss-independent, confirming the importance of peripheral endocannabinoid system effects in addition to central effects.

  17. How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

    International Nuclear Information System (INIS)

    Hu Longhua; Papoian, Garegin A

    2011-01-01

    Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.

  18. Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection.

    Science.gov (United States)

    Castellano, Laura M; Bart, Stephen M; Holmes, Veronica M; Weissman, Drew; Shorter, James

    2015-08-20

    Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (semen-derived enhancer of viral infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104(A503V), directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection, and could have therapeutic utility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Androgen Receptor Antagonism By Divalent Ethisterone Conjugates In Castrate-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Levine, Paul M.; Lee, Eugine; Greenfield, Alex; Bonneau, Richard; Logan, Susan K.; Garabedian, Michael J.; Kirshenbaum, Kent

    2013-01-01

    Sustained treatment of prostate cancer with Androgen Receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, new therapeutic regimens that target and modulate AR activity could prove beneficial. We previously introduced a versatile chemical platform to generate competitive and non-competitive multivalent peptoid oligomer conjugates that modulate AR activity. In particular, we identified a linear and a cyclic divalent ethisterone conjugate that exhibit potent anti-proliferative properties in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we characterize the mechanism of action of these compounds utilizing confocal microscopy, time-resolved fluorescence resonance energy transfer, chromatin immunoprecipitation, flow cytometry, and microarray analysis. The linear conjugate competitively blocks AR action by inhibiting DNA binding. In addition, the linear conjugate does not promote AR nuclear localization or co-activator binding. In contrast, the cyclic conjugate promotes AR nuclear localization and induces cell-cycle arrest, despite its inability to compete against endogenous ligand for binding to AR in vitro. Genome-wide expression analysis reveals that gene transcripts are differentially affected by treatment with the linear or cyclic conjugate. Although the divalent ethisterone conjugates share extensive chemical similarities, we illustrate that they can antagonize the AR via distinct mechanisms of action, establishing new therapeutic strategies for potential applications in AR pharmacology. PMID:22871957

  20. ANTAGONISM OF PROGESTERONE RECEPTOR SUPPRESSES CAROTID BODY RESPONSES TO HYPOXIA AND NICOTINE IN RAT PUPS

    Science.gov (United States)

    JOSEPH, V.; NIANE, L. M.; BAIRAM, A.

    2013-01-01

    We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between post-natal days 3 and 15. In 11–14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity—nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats. PMID:22326965

  1. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    DEFF Research Database (Denmark)

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

    2011-01-01

    Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

  2. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    Science.gov (United States)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  3. Glutathione and the Antioxidant Potential of Binary Mixtures with Flavonoids: Synergisms and Antagonisms

    Directory of Open Access Journals (Sweden)

    Patrícia Valentão

    2013-07-01

    Full Text Available Polyphenols are able to trap free radicals, which contributes to their known antioxidant capacity. In plant extracts, these secondary metabolites may act in concert, in a way that their combined activities will be superior to their individual effects (synergistic interaction. Several polyphenols have demonstrated clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. As so, the intake of these compounds at certain concentrations in the diet and/or supplementation may potentiate the activity of reduced form glutathione (GSH, thus better fighting oxidative stress. The aim of this work was to predict a structure-antioxidant activity relationship using different classes of flavonoids and to assess, for the first time, possible synergisms and antagonisms with GSH. For these purposes a screening microassay involving the scavenging of DPPH• was applied. In general, among the tested compounds, those lacking the catechol group in B ring showed antagonistic behaviour with GSH. Myricetin displayed additive effect, while quercetin, fisetin, luteolin, luteolin-7-O-glucoside, taxifolin and (+-catechin demonstrated synergistic actions. Furthermore, adducts formed at C2′ and C5′ of the B ring seem to be more important for the antioxidant capacity than adducts formed at C6 and C8 of the A ring.

  4. Action of Bacopa monnieri to antagonize cisplatin-induced emesis in Suncus murinus (house musk shrew

    Directory of Open Access Journals (Sweden)

    Ihsan Ullah

    2017-04-01

    Full Text Available Bacopa monnieri (BM, family Scrophulariaceae is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr and BM n-butanol fractions (BM-ButFr to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew. Cisplatin (30 mg/kg, i.p. reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10–40 mg/kg, s.c. and BM-ButFr (5–20 mg/kg, s.c. antagonized the retching and/or vomiting response by ∼59.4% (p  0.05. In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of chemotherapy-induced emesis in man.

  5. Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation

    Directory of Open Access Journals (Sweden)

    Mauricio Cortes

    2015-10-01

    Full Text Available Hematopoietic stem and progenitor cells (HSPCs are born from hemogenic endothelium in the dorsal aorta. Specification of this hematopoietic niche is regulated by a signaling axis using Hedgehog (Hh and Notch, which culminates in expression of Runx1 in the ventral wall of the artery. Here, we demonstrate that the vitamin D precursor cholecalciferol (D3 modulates HSPC production by impairing hemogenic vascular niche formation. Accumulation of D3 through exogenous treatment or inhibition of Cyp2r1, the enzyme required for D3 25-hydroxylation, results in Hh pathway antagonism marked by loss of Gli-reporter activation, defects in vascular niche identity, and reduced HSPCs. Mechanistic studies indicated the effect was specific to D3, and not active 1,25-dihydroxy vitamin D3, acting on the extracellular sterol-binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis on cell fate commitment and maturation in Hh-regulated tissues, which may have implications beyond hemogenic endothelium specification.

  6. Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Takla Griss

    2015-12-01

    Full Text Available Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC. However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity.

  7. Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum.

    Science.gov (United States)

    Lai, Cora Sau-Wan; Yu, Man-Shan; Yuen, Wai-Hung; So, Kwok-Fai; Zee, Sze-Yong; Chang, Raymond Chuen-Chung

    2008-01-23

    Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi) is a medicinal fungus used clinically in many Asian countries to promote health and longevity. Synaptic degeneration is another key mode of neurodegeneration in Alzheimer's disease (AD). Recent studies have shown the loss of synaptic density proteins in each individual neuron during the progression of AD. It was recently reported that beta-amyloid (Abeta) could cause synaptic dysfunction and contribute to AD pathology. In this study, we reported that aqueous extract of G. lucidum significantly attenuated Abeta-induced synaptotoxicity by preserving the synaptic density protein, synaptophysin. In addition, G. lucidum aqueous extract antagonized Abeta-triggered DEVD cleavage activities in a dose-dependent manner. Further studies elucidated that phosphorylation of c-Jun N-terminal kinase, c-Jun, and p38 MAP kinase was attenuated by G. lucidum in Abeta-stressed neurons. Taken together, the results prove a hypothesis that anti-aging G. lucidum can prevent harmful effects of the exterminating toxin Abeta in AD.

  8. Effect of blockage of the endocannabinoid system by CB(1) antagonism on cardiovascular risk.

    Science.gov (United States)

    Mach, François; Montecucco, Fabrizio; Steffens, Sabine

    2009-01-01

    The endocannabinoid system is a crucial player in the inflammatory processes underlying atherosclerosis. Recently, basic research studies and animal models have strongly supported the role of the endocannabinoid system not only in the regulation of classical cardiovascular risk factors (including lipid profile and glucose homeostasis), but also in the activation of immune cells and inflammatory mediators. Clinical trials investigating treatment with rimonabant (a selective antagonist of the cannabinoid type 1 receptor) have suggested a beneficial effect of this drug in the management of obesity. Further studies are needed to explore a possible use for rimonabant in treating type 2 diabetes and acute and chronic cardiovascular disease. Despite the slight increase in adverse events (mainly psychiatric), which has led to the recent withdrawal of rimonabant from the market, CB(1) receptor antagonism might represent a very promising therapeutic strategy to reduce the cardiovascular risk. In the present review, we focused on the most important experimental investigations into the role of the endocannabinoid system in atherosclerosis and cardiovascular risk.

  9. Antagonism of Apis mellifera and Melipona beecheii for the sources of feeding

    Directory of Open Access Journals (Sweden)

    Ailyn Leal-Ramos

    2013-12-01

    Full Text Available The competition is defined as the interrelation among species that influence negatively in the abundance or the growth of the population of an or both species. They can be defined two competition types: competition of exploitation for the use of a resource shared as the food and the competition by interference when decreases the efficiency of exploitation of another species for the competition for the territory. With the objective of determining the possible antagonism of A. mellifera and M. beecheii for the source of pollen, the origin of the pollen stored in the reservations of foods of the beehives of A. mellifera and M. beecheii through palinologic analysis carried out to samples of pollen of both species of bees settled down. The diversity of pollen found in the samples is superior in A. mellifera with regard to M. beecheii being Mimosa pudica and Mimosa pigra the identified species with a high frequency. On the other hand, 71,4% of the vegetable identified species coincides in the pollen found in the samples of A. mellifera and M. beecheii, being a half similarity among the grains of pollen of the beehives of both species expressed by a coefficient of similarity of Jaccard 0,5219.

  10. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  11. Mxi1 and Mxi1-0 Antagonize N-Myc Function and Independently Mediate Apoptosis in Neuroblastoma

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    David A. Erichsen

    2015-02-01

    Full Text Available Neuroblastoma (NB is the third most common malignancy of childhood, and outcomes for children with advanced disease remain poor; amplification of the MYCN gene portends a particularly poor prognosis. Mxi1 antagonizes N-Myc by competing for binding to Max and E-boxes. Unlike N-Myc, Mxi1 mediates transcriptional repression and suppresses cell proliferation. Mxi1 and Mxi1-0 (an alternatively transcribed Mxi1 isoform share identical Max and DNA binding domains but differ in amino-terminal sequences. Because of the conservation of these critical binding domains, we hypothesized that Mxi1-0 antagonizes N-Myc activity similar to Mxi1. SHEP NB cells and SHEP cells stably transfected with MYCN (SHEP/MYCN were transiently transfected with vectors containing full-length Mxi1, full-length Mxi1-0, or the common Mxi domain encoded by exons 2 to 6 (ex2-6. After incubation in low serum, parental SHEP/MYCN cell numbers were reduced compared with SHEP cells. Activated caspase-3 staining and DNA fragmentation ELISA confirmed that SHEP/MYCN cells undergo apoptosis in low serum, while SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 do not. However, SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 and grown in normal serum showed proliferation rates similar to SHEP cells. Mxi ex2-6 did not affect cell number in low or normal serum, suggesting that amino terminal domains of Mxi1 and Mxi1-0 are critical for antagonism. In the absence of N-Myc, Mxi1 and Mxi1-0 induce apoptosis independently through the caspase-8–dependent extrinsic pathway, while N-Myc activates the caspase-9–dependent intrinsic pathway. Together, these data indicate that Mxi1 and Mxi1-0 antagonize N-Myc but also independently impact NB cell survival.

  12. Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

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    Fleischmann, Thea; Jirkof, Paulin; Henke, Julia; Arras, Margarete; Cesarovic, Nikola

    2016-08-01

    Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole. © The Author(s) 2016.

  13. Antagonism in the extraction of uranium(VI) by the binary mixture of PC88A and benzimidazole

    International Nuclear Information System (INIS)

    Mukherjee, A.; Kamila, S.; Chakravortty, V.

    1999-01-01

    Extraction studies of uranium(VI) by the binary mixture of PC88A and benzimidazole show an antagonistic behavior in the concentration range 10 -5 -10 -6 M of PC88A and 0.005M of benzimidazole. Antagonism is observed due to the deprotonation of PC88A by benzimidazole forming an adduct resulting in the virtual removal of PC88A from the system. (author)

  14. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

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    Yan Deng

    2015-01-01

    Conclusions: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  15. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

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    Jennifer M. Monk

    2014-01-01

    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  16. Histamine H3 receptors and its antagonism as a novel mechanism for antipsychotic effect: a current preclinical & clinical perspective.

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    Mahmood, Danish

    2016-10-01

    Histamine H 3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H 3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia. These medications works through diverse mechanisms which include agonism at metabotropic glutamate receptor (mGluR2/3), partial agonism at dopamine D 2 , D 3 and serotonin 5-HT 1A receptors, antagonism at D 2 , 5-HT 2A, 5-HT 2B and 5-HT 7 receptors, combined dopamine antagonism with GABA agonist activity, inhibition of monoamine oxidase-B, modulation of oestrogen receptor, and activation of nuclear retinoid X receptor. However, still specific safe therapy for psychosis remains at large. Schizophrenia is a severe neuropsychiatric disorder result both from hyper- and hypo-dopaminergic transmission causing positive and negative symptoms, respectively. Pharmacological stimulation of dopamine release in the prefrontal cortex has been a viable approach in treating negative symptoms and cognitive deficits of schizophrenia symptoms that are currently not well treated and continue to represent significant unmet medical challenges. Administration of H 3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H 3 receptor may be a potential target for treating negative symptoms and cognitive deficits associated with schizophrenia. Further, insights are emerging into the potential role of histamine H 3 receptors as a target of antiobesity

  17. ANTAGONISM OF A. VIRIDANS TO CONDITIONALLY - PATHOGENIC MICROFLORA OF THE NOSE AND OROPHARYNX OF CHILDREN WITH CARDIAC PATOLOGY

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    Stepansky D.O.

    2015-12-01

    Full Text Available Introduction. Search for harmless and simultaneously effective probiotics, which could be successfully used for treatment and prevention of infectious deseases, is currently important. A. viridans is of particular interest, as it is representative of the normal microflora of human with broad spectrum of antibacterial action. The use of this microorganism has a number of advantages: the absence of side effects on the body; high adhesive abilities; resistance to lysozyme in saliva; the ability of use in patients, sensitized to antibiotics and chemotherapeutic drugs; stimulation effects on the human immune system. Material and methods. The purpose of the study was to investigate the antagonism of A. viridans № 167 and autostrains of aerococcuses, isolated at patients, to conditionally - pathogenic microflora of the nose and oropharynx of children with cardiac patology. At the first stage of the study the microflora of the of the nose and oropharynx of 2 investigated categories was examined – 40 children 4-14 years with cardiac patology and 40 healthy children 4-5 years old. The second stage of work was to study the effect of A. viridans on the explored strains. Results and discussion. A. viridans manifests the antagonism to all studied strains of gram-positive and gram-negative microorganisms, except C. albisans. A. viridans antagonistic activity to staphylococci (10 + 3 mm and streptococci (10 + 2mm is at the approximately same level. It is interesting to compare the antagonism of aerococcuses to clinical isolates of S. pyogenes and similar strains from carriers (healthy children category. Impact of aerococcuses on P. mirabilis strain appeared at the highest level. Autosimbionts of A. viridans, isolated from healthy children, are more antagonistic to CPM strains, isolated from these children, than autostrains of A. viridans, isolated from children with with cardiac patology, and higher than the museum strain of A. viridans № 167 antagonism

  18. Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

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    Yu-Chun Wang

    2013-11-01

    Full Text Available Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME. Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv significantly decreased blood pressure of rabbits and NA or DTC injection (iv did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO, but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

  19. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy.

    Science.gov (United States)

    Oelkrug, Rebecca; Herrmann, Beate; Geissler, Cathleen; Harder, Lisbeth; Koch, Christiane; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Mittag, Jens

    2017-10-01

    Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments. We sought to test the consequences of maternal α1-adrenergic antagonism during pregnancy, which can occur e.g. during hypertension treatment, for the endocrine and metabolic phenotype of the offspring. We treated C57BL/6NCrl female mice with the α1-adrenergic antagonist prazosin during pregnancy and analyzed the male and female offspring for endocrine and metabolic abnormalities. Our data revealed that maternal α1-adrenergic blockade caused dwarfism, elevated body temperature, and insulin resistance in male offspring, accompanied by reduced IGF-1 serum concentrations as the result of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently identified increased CpG DNA methylation at the transcriptional start site of the alternative Ghr promotor caused by the maternal treatment, which showed a strong inverse correlation to hepatic Ghr expression. Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  20. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

    International Nuclear Information System (INIS)

    Horber, F.F.; Marsh, H.M.; Haymond, M.W.

    1991-01-01

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation 14 C leucine increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment

  1. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito; Takahashi, Satoru

    2015-07-17

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.

  2. Antagonism of CD11b with neutrophil inhibitory factor (NIF inhibits vascular lesions in diabetic retinopathy.

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    Alexander A Veenstra

    Full Text Available Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1, a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF, a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2 by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response.

  3. 5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats.

    Science.gov (United States)

    Sukoff Rizzo, Stacey J; Pulicicchio, Claudine; Malberg, Jessica E; Andree, Terrance H; Stack, Gary P; Hughes, Zoë A; Schechter, Lee E; Rosenzweig-Lipson, Sharon

    2009-09-01

    Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapies. 5-HT(1A) antagonists have been suggested as beneficial adjunctive treatment in respect of antidepressant efficacy; however, the effects of 5-HT(1A) antagonism on antidepressant-induced side-effects has not been fully examined. The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT(1A) antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls. Acute administration of the 5-HT(1A) antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines. Chronic co-administration of the 5-HT(1A) antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats. Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT(1A) antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT(1A) antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.

  4. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells.

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    James R Bowen

    2017-02-01

    Full Text Available Zika virus (ZIKV is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target.

  5. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory & urological disorders

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    Anthony eFord

    2013-12-01

    Full Text Available A sensory role for ATP was proposed long before general acceptance of its extracellular role. ATP activates & sensitizes signal transmission at multiple sites along the sensory axis, across multiple synapses. P2X & P2Y receptors mediate ATP modulation of sensory pathways & participate in dysregulation, where ATP action directly on primary afferent neurons (PANs, linking receptive field to CNS, has received much attention. Many PANs, especially C-fibers, are activated by ATP, via P2X3-containing trimers. P2X3 knock-out mice & knock-down in rats led to reduced nocifensive activity & visceral reflexes, suggesting that antagonism may offer benefit in sensory disorders. Recently, drug-like P2X3 antagonists, active in a many inflammatory & visceral pain models, have emerged. Significantly, these compounds have no overt CNS action & are inactive versus acute nociception. Selectively targeting ATP sensitization of PANs may lead to therapies that block inappropriate chronic signals at their source, decreasing drivers of peripheral & central wind-up, yet leaving defensive nociceptive and brain functions unperturbed. This article reviews this evidence, focusing on how ATP sensitization of PANs in visceral hollow organs primes them to chronic discomfort, irritation & pain (symptoms as well as exacerbated autonomic reflexes (signs, & how the use of isolated organ-nerve preparations has revealed this mechanism. Urinary & airways systems share many features: dependence on continuous afferent traffic to brainstem centers to coordinate efferent autonomic outflow; loss of descending inhibitory influence in functional & sensory disorders; dependence on ATP in mediating sensory responses to diverse mechanical and chemical stimuli; a mechanistically overlapping array of existing medicines for pathological conditions. These similarities may also play out in terms of future treatment of signs & symptoms, in the potential for benefit of P2X3 antagonists.

  6. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis

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    Prema Robinson

    2015-01-01

    Full Text Available Viral-myocarditis is an important cause of heart failure for which no specific treatment is available. We previously showed the neuropeptide substance P (SP is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV. The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA, will be beneficial in viral-myocarditis. Aprepitant (1.2 mg/kg, a SP-receptor antagonist, or fasudil (10 mg/kg, a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection. Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels (P<0.05 all, ANOVA. Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity (P<0.05 all, ANOVA. Pre- or posttreatment with fasudil did not significantly impact disease manifestations. These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway. These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis.

  7. ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

    Science.gov (United States)

    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

    2013-09-01

    NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.

  8. Dynamics of bounded confidence opinion in heterogeneous social networks: Concord against partial antagonism

    Science.gov (United States)

    Kurmyshev, Evguenii; Juárez, Héctor A.; González-Silva, Ricardo A.

    2011-08-01

    Bounded confidence models of opinion dynamics in social networks have been actively studied in recent years, in particular, opinion formation and extremism propagation along with other aspects of social dynamics. In this work, after an analysis of limitations of the Deffuant-Weisbuch (DW) bounded confidence, relative agreement model, we propose the mixed model that takes into account two psychological types of individuals. Concord agents (C-agents) are friendly people; they interact in a way that their opinions always get closer. Agents of the other psychological type show partial antagonism in their interaction (PA-agents). Opinion dynamics in heterogeneous social groups, consisting of agents of the two types, was studied on different social networks: Erdös-Rényi random graphs, small-world networks and complete graphs. Limit cases of the mixed model, pure C- and PA-societies, were also studied. We found that group opinion formation is, qualitatively, almost independent of the topology of networks used in this work. Opinion fragmentation, polarization and consensus are observed in the mixed model at different proportions of PA- and C-agents, depending on the value of initial opinion tolerance of agents. As for the opinion formation and arising of “dissidents”, the opinion dynamics of the C-agents society was found to be similar to that of the DW model, except for the rate of opinion convergence. Nevertheless, mixed societies showed dynamics and bifurcation patterns notably different to those of the DW model. The influence of biased initial conditions over opinion formation in heterogeneous social groups was also studied versus the initial value of opinion uncertainty, varying the proportion of the PA- to C-agents. Bifurcation diagrams showed an impressive evolution of collective opinion, in particular, radical changes of left to right consensus or vice versa at an opinion uncertainty value equal to 0.7 in the model with the PA/C mixture of population near 50/50.

  9. Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy.

    Science.gov (United States)

    Veenstra, Alexander A; Tang, Jie; Kern, Timothy S

    2013-01-01

    Leukocytes and proteins that govern leukocyte adhesion to endothelial cells play a causal role in retinal abnormalities characteristic of the early stages of diabetic retinopathy, including diabetes-induced degeneration of retinal capillaries. Leukocyte integrin αmβ2 (CD11b/CD18, MAC1), a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated leukocytes in vitro. We hypothesized that Neutrophil Inhibitory Factor (NIF), a selective antagonist of integrin αmβ2, would inhibit the diabetes-induced degeneration of retinal capillaries by inhibiting the excessive interaction between leukocytes and retinal endothelial cells in diabetes. Wild type animals and transgenic animals expressing NIF were made diabetic with streptozotocin and assessed for diabetes-induced retinal vascular abnormalities and leukocyte activation. To assess if the leukocyte blocking therapy compromised the immune system, animals were challenged with bacteria. Retinal superoxide production, leukostasis and leukocyte superoxide production were increased in wild type mice diabetic for 10 weeks, as was the ability of leukocytes isolated from diabetic animals to kill retinal endothelial cells in vitro. Retinal capillary degeneration was significantly increased in wild type mice diabetic 40 weeks. In contrast, mice expressing NIF did not develop any of these abnormalities, with the exception that non-diabetic and diabetic mice expressing NIF generated greater amounts of superoxide than did similar mice not expressing NIF. Importantly, NIF did not significantly impair the ability of mice to clear an opportunistic bacterial challenge, suggesting that NIF did not compromise immune surveillance. We conclude that antagonism of CD11b (integrin αmβ2) by NIF is sufficient to inhibit early stages of diabetic retinopathy, while not compromising the basic immune response.

  10. Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.

    Science.gov (United States)

    Dandash, Orwa; Harrison, Ben J; Adapa, Ram; Gaillard, Raphael; Giorlando, Francesco; Wood, Stephen J; Fletcher, Paul C; Fornito, Alex

    2015-02-01

    The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.

  11. Cerebral, spinal and peripheral inhibition of gastrointestinal transit by PI017: differential antagonism by naloxonazine

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C.L.; Heyman, J.S.; Porreca, F.; Burks, T.F.

    1986-03-05

    The authors were interested in characterizing the relative importance of central (cerebral, spinal) and peripheral opioid receptors in inhibition of gastrointestinal transit. The mu-receptor selective agonist, (NMePhe/sup 3/,D-Pro/sup 4/)morphiceptin (PL017), was evaluated for its effectiveness in slowing gastrointestinal transit after subcutaneous, intracerebroventricular (i.c.v.) or intrathecal (i.th.) administration when given alone or after pretreatment with naloxonazine, an irreversible mu/sub 1/ selective opioid receptor antagonist. Male, ICR mice (20-25 g) were pretreated with saline, naloxone or naloxonazine (35 mg/kg, s.c.) 25 hr prior to testing. Gastrointestinal transit was evaluated in previously fasted (18 hr) mice by oral administration of a liquid radiolabelled marker (Na/sub 2//sup 51/CrO/sub 4/). I.th. PL017 (100-1000 ng) was effective in slowing transit, but was essentially insensitive to naloxone or naloxonazine pretreatment. PL017 produced a dose-related inhibition of transit when given by either the i.c.v. (100-1000 ng) or s.c.(1-10 mg/kg) route; this effect was not sensitive to naloxone pretreatment but was antagonized by naloxonazine. These results indicate that the opioid receptors mediating gastrointestinal transit in the brain and periphery may be mu/sub 1/. In contrast, the insensitivity to naloxonazine suggests that the gastrointestinal effects of PL017 in the spinal cord may be the result of activation of mu/sub 2/ or possibly delta opioid receptors.

  12. ANTAGONISM AGAINST VIBRIO CHOLERAE BY BACTERIAL DIFFUSIBLE COMPOUND IN THE FECAL MICROBIOTA OF RODENTS

    Directory of Open Access Journals (Sweden)

    Silva Simone Helena da

    1998-01-01

    Full Text Available In an ex vivo agar plate assay, we monitored the appearance of an inhibitory halo against Vibrio cholerae from the feces of Wistar and Fischer rats aged 10 to 42 days. The frequency of Wistar rats showing halo increased from 0% (10 days to a maximum of 80.0% (29 days and then decreased to 53.3% (42 days. A similar pattern was obtained with Fischer rats but with a lower intensity (maximum frequency of 50.0% by day 36. In a separate experiment, when Wistar rats were fed a low-protein diet for 7 days, the inhibitory halo decreased drastically. Three apparently different colony morphologies were isolated from the dominant fecal microbiota: a facultative anaerobe (FAN and two strict anaerobes (SAN. The ex vivo inhibitory test showed a halo around the feces of germfree mice monoassociated with the FAN bacterium or one of the SAN bacterium but not of the germfree ones. After oral challenge of all groups with V. cholerae, a permissive and a drastic barrier effects were observed in mice with FAN and SAN associated bacteria, respectively. The FAN and one SAN bacteria used in the in vivo challenges were identified as Escherichia coli and Streptococcus intermedius, respectively. The potent antagonism developed by the rat intestinal microbiota against V. cholerae seems to be due, in part, to diffusible compounds and this phenomenon depends apparently on age, strain and nutrition of the animals. These preliminary results also suggest that this effect was due to more than one bacterial component at any given moment.

  13. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

    International Nuclear Information System (INIS)

    Montrose, Kristopher; Krissansen, Geoffrey W.

    2014-01-01

    Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC

  14. Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at receptor-binding interfaces

    Directory of Open Access Journals (Sweden)

    Brown Scott

    2010-07-01

    Full Text Available Abstract Background Interleukin-4 (IL4 is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths 1. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. Results This analysis revealed evidence of diversifying selection at 15 residues, clustered in epitopes responsible for IL4 binding to its Type I and Type II receptors. Such a striking signature of selective pressure suggested either recurrent episodes of pathogen antagonism or ligand/receptor co-evolution. To test the latter possibility, we performed detailed functional analysis of IL4 allotypes expressed by Mus musculus musculus and Mus musculus castaneus, which happen to differ at 5 residues (including three at positively selected sites in and adjacent to the site 1 epitope that binds the IL4Rα subunit shared by the Type I and Type II IL4 receptors. We show that this intra-species variation affects the ability of IL4 neither to bind IL4 receptor alpha (IL4Rα nor to signal biological responses through its Type I receptor. Conclusions Our results -- reminiscent of clustered positively selected sites revealing functionally important residues at host-virus interaction interfaces -- are consistent with IL4 having evolved to avoid recurrent pathogen antagonism, while maintaining the capacity to bind and signal through its cognate receptor. This work exposes what may be a general feature of evolutionary conflicts fought by pathogen antagonists at host protein-protein interaction interfaces involved in immune signaling: the emergence of receptor-binding ligand epitopes capable of buffering amino acid variation.

  15. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

    Energy Technology Data Exchange (ETDEWEB)

    Montrose, Kristopher; Krissansen, Geoffrey W., E-mail: gw.krissansen@auckland.ac.nz

    2014-10-31

    Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC.

  16. Hydrogen sulfide alleviates postharvest ripening and senescence of banana by antagonizing the effect of ethylene.

    Directory of Open Access Journals (Sweden)

    Yun Ge

    Full Text Available Accumulating evidence shows that hydrogen sulfide (H2S acts as a multifunctional signaling molecule in plants, whereas the interaction between H2S and ethylene is still unclear. In the present study we investigated the role of H2S in ethylene-promoted banana ripening and senescence by the application of ethylene released from 1.0 g·L-1 ethephon solution or H2S with 1 mM sodium hydrosulfide (NaHS as the donor or in combination. Fumigation with ethylene was found to accelerate banana ripening and H2S treatment effectively alleviated ethylene-induced banana peel yellowing and fruit softening in parallel with decreased activity of polygalacturonase (PG. Ethylene+H2S treatment also delayed the decreases in chlorophyll and total phenolics, and increased the accumulation of flavonoid, whereas decreased the contents of carotenoid, soluble protein in banana peel and reducing sugar in pulp compared with ethylene treatment alone. Besides, ethylene+H2S treatment suppressed the accumulation of superoxide radicals (·O2-, hydrogen peroxide (H2O2 and malondialdehyde (MDA which accumulated highly in ethylene-treated banana peels. Furthermore H2S enhanced total antioxidant capacity in ethylene-treated banana peels with the 2,2'-azobis(3-ethylbenz-thiazoline-6-sulfonic acid (ABTS assay. The result of quantitative real-time PCR showed that the combined treatment of ethylene with H2S down-regulated the expression of ethylene synthesis genes MaACS1, MaACS2 and MaACO1 and pectate lyase MaPL compared with ethylene treatment, while the expression of ethylene receptor genes MaETR, MaERS1 and MaERS2 was enhanced in combination treatment compared with ethylene alone. In all, it can be concluded that H2S alleviates banana fruit ripening and senescence by antagonizing the effect of ethylene through reduction of oxidative stress and inhibition of ethylene signaling pathway.

  17. Hydrogen sulfide alleviates postharvest ripening and senescence of banana by antagonizing the effect of ethylene.

    Science.gov (United States)

    Ge, Yun; Hu, Kang-Di; Wang, Sha-Sha; Hu, Lan-Ying; Chen, Xiao-Yan; Li, Yan-Hong; Yang, Ying; Yang, Feng; Zhang, Hua

    2017-01-01

    Accumulating evidence shows that hydrogen sulfide (H2S) acts as a multifunctional signaling molecule in plants, whereas the interaction between H2S and ethylene is still unclear. In the present study we investigated the role of H2S in ethylene-promoted banana ripening and senescence by the application of ethylene released from 1.0 g·L-1 ethephon solution or H2S with 1 mM sodium hydrosulfide (NaHS) as the donor or in combination. Fumigation with ethylene was found to accelerate banana ripening and H2S treatment effectively alleviated ethylene-induced banana peel yellowing and fruit softening in parallel with decreased activity of polygalacturonase (PG). Ethylene+H2S treatment also delayed the decreases in chlorophyll and total phenolics, and increased the accumulation of flavonoid, whereas decreased the contents of carotenoid, soluble protein in banana peel and reducing sugar in pulp compared with ethylene treatment alone. Besides, ethylene+H2S treatment suppressed the accumulation of superoxide radicals (·O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) which accumulated highly in ethylene-treated banana peels. Furthermore H2S enhanced total antioxidant capacity in ethylene-treated banana peels with the 2,2'-azobis(3-ethylbenz-thiazoline-6-sulfonic acid (ABTS) assay. The result of quantitative real-time PCR showed that the combined treatment of ethylene with H2S down-regulated the expression of ethylene synthesis genes MaACS1, MaACS2 and MaACO1 and pectate lyase MaPL compared with ethylene treatment, while the expression of ethylene receptor genes MaETR, MaERS1 and MaERS2 was enhanced in combination treatment compared with ethylene alone. In all, it can be concluded that H2S alleviates banana fruit ripening and senescence by antagonizing the effect of ethylene through reduction of oxidative stress and inhibition of ethylene signaling pathway.

  18. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    , but antagonistically on BT-474 cells. A representative anti-HER2 antibody inhibited Akt and ERK1/2 phosphorylation leading to cyclin D1 accumulation and growth arrest in SK-BR-3 cells, independently from TNF-α. Conclusions Novel antibodies against extracellular domain of HER2 may serve as potent anti-cancer bioactive molecules. Cell-dependent synergy and antagonism between anti-HER2 antibodies and TNF-α provide evidence for a complex interplay between HER2 and TNF-α signaling pathways. Such complexity may drastically affect the outcome of HER2-directed therapeutic interventions.

  19. Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1.

    Science.gov (United States)

    Gaude, H; Aznar, N; Delay, A; Bres, A; Buchet-Poyau, K; Caillat, C; Vigouroux, A; Rogon, C; Woods, A; Vanacker, J-M; Höhfeld, J; Perret, C; Meyer, P; Billaud, M; Forcet, C

    2012-03-22

    LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase STRAD (STE-20-related pseudokinase) and the scaffolding protein MO25, the formation of this heterotrimeric complex promotes allosteric activation of LKB1. We have previously reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and stabilizes LKB1. Combining pharmacological studies and RNA interference approaches, we now provide evidence that the co-chaperone Cdc37 participates to the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex recognizes a surface within the N-terminal catalytic lobe of client protein kinases. In agreement with this finding, we found that the chaperones Hsp90 and Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with recombinant proteins revealed that the former is catalytically active whereas the latter is inactive. Furthermore, consistent with a documented repressor function of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken together, our results establish that the Hsp90-Cdc37 complex controls both the stability and activity of the LKB1 kinase. This study further shows that two chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP, finely control the cellular level of LKB1 protein.

  20. Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

    2017-06-01

    The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3

  1. Detection of Fusarium spp. and Trichoderma spp. and antagonism of Trichoderma sp. in soybean under no-tillage

    OpenAIRE

    Paola Mendes Milanesi; Elena Blume; Marlove Fátima Brião Muniz; Lia Rejane Silveira Reiniger; Zaida Inês Antoniolli; Emanuele Junges; Manoeli Lupatini

    2013-01-01

    This study aimed i) to quantify the occurrence of Fusarium spp. and Trichoderma spp. in rhizospheric soil, with and without symptoms of Sudden Death Syndrome (SDS) in eight soybean genotypes; ii) morphologically identify isolates of Fusarium spp. from roots with SDS; iii) evaluate the antagonism between Trichoderma spp. and Fusarium spp. isolates from rhizospheric soil and roots from with and without SDS, respectively; and iv) characterize through the ITS1-5.8S-ITS2 region of rDNA the isolate...

  2. 77 FR 59106 - Glufosinate Ammonium; Pesticide Tolerances

    Science.gov (United States)

    2012-09-26

    ... response to the notices of filing. Based upon review of the data supporting the petition, EPA is: (1... 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support... sensitizer. Subchronic toxicity studies in rats showed inhibition of glutamate synthetase and lead the Agency...

  3. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.

    Science.gov (United States)

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang; Jia, Shuang; Kaldunski, Mary L; Greenbaum, Carla J; Mandrup-Poulsen, Thomas; Hessner, Martin J

    2016-04-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1α and IL-1β additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhihong; Zhang, Yuxia [Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States); Wang, Li, E-mail: l.wang@hsc.utah.edu [Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Mdm2 enhances HNF4{alpha} activation of the ApoCIII promoter via interaction with HNF4{alpha}. Black-Right-Pointing-Pointer p53 antagonizes the effect of Mdm2 activation of the ApoCIII promoter. Black-Right-Pointing-Pointer SHP strengthens p53 inhibition but abolishes Mdm2 activation of the ApoCIII promoter. Black-Right-Pointing-Pointer Mdm2 alters the enrichment of HNF4{alpha}, p53 and SHP to the ApoCIII promoter. -- Abstract: We examined the effect of Mdm2 on regulation of the ApoCIII promoter and its cross-talk with p53 and nuclear receptor SHP. Overexpression of Mdm2 markedly enhanced ApoCIII promoter activity by HNF4{alpha}. A direct association of Mdm2 protein with the HNF4{alpha} protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4{alpha} activation of the ApoCIII promoter and antagonized the effect of Mdm2. Co-expression of SHP further strengthened p53 inhibition and abolished Mdm2 activation of the ApoCIII promoter. Mdm2 inhibited p53-mediated enrichment of HNF4{alpha} to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter. The results from this study implicate a potentially important function of Mdm2 in regulation of lipoprotein metabolism.

  5. Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition

    International Nuclear Information System (INIS)

    Yang, Zhihong; Zhang, Yuxia; Wang, Li

    2012-01-01

    Highlights: ► Mdm2 enhances HNF4α activation of the ApoCIII promoter via interaction with HNF4α. ► p53 antagonizes the effect of Mdm2 activation of the ApoCIII promoter. ► SHP strengthens p53 inhibition but abolishes Mdm2 activation of the ApoCIII promoter. ► Mdm2 alters the enrichment of HNF4α, p53 and SHP to the ApoCIII promoter. -- Abstract: We examined the effect of Mdm2 on regulation of the ApoCIII promoter and its cross-talk with p53 and nuclear receptor SHP. Overexpression of Mdm2 markedly enhanced ApoCIII promoter activity by HNF4α. A direct association of Mdm2 protein with the HNF4α protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4α activation of the ApoCIII promoter and antagonized the effect of Mdm2. Co-expression of SHP further strengthened p53 inhibition and abolished Mdm2 activation of the ApoCIII promoter. Mdm2 inhibited p53-mediated enrichment of HNF4α to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter. The results from this study implicate a potentially important function of Mdm2 in regulation of lipoprotein metabolism.

  6. MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Schafer, Alexandra; Burnum-Johnson, Kristin E.; Mitchell, Hugh D.; Eisfeld-Fenney, Amie J.; Walters, Kevin B.; Nicora, Carrie D.; Purvine, Samuel O.; Casey, Cameron P.; Monroe, Matthew E.; Weitz, Karl K.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gralinski, Lisa; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Sims, Amy C.; Kawaoka, Yoshihiro; Baric, Ralph

    2018-01-16

    Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways in order to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems based approach, we examined differential regulation of IFNγ dependent genes following infection with highly pathogenic viruses including influenza (H5N1-VN1203, H1N1-CA04) and coronaviruses (SARS-CoV, MERS-CoV). Categorizing by function, we observed down regulation of genes associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down regulation of antigen presentation genes and was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation rather than histone modification plays a crucial role in MERS-CoV mediated antagonism of antigen presentation genes; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common approach utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.

  7. Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex

    Science.gov (United States)

    Toriumi, Kazuya; Mouri, Akihiro; Narusawa, Shiho; Aoyama, Yuki; Ikawa, Natsumi; Lu, Lingling; Nagai, Taku; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

    2012-01-01

    N-methyl--aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression. PMID:22257896

  8. Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.

    Science.gov (United States)

    Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

    2015-12-01

    Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

  9. Alternative binding modes identified for growth and differentiation factor-associated serum protein (GASP) family antagonism of myostatin.

    Science.gov (United States)

    Walker, Ryan G; Angerman, Elizabeth B; Kattamuri, Chandramohan; Lee, Yun-Sil; Lee, Se-Jin; Thompson, Thomas B

    2015-03-20

    Myostatin, a member of the TGF-β family of ligands, is a strong negative regulator of muscle growth. As such, it is a prime therapeutic target for muscle wasting disorders. Similar to other TGF-β family ligands, myostatin is neutralized by binding one of a number of structurally diverse antagonists. Included are the antagonists GASP-1 and GASP-2, which are unique in that they specifically antagonize myostatin. However, little is known from a structural standpoint describing the interactions of GASP antagonists with myostatin. Here, we present the First low resolution solution structure of myostatin-free and myostatin-bound states of GASP-1 and GASP-2. Our studies have revealed GASP-1, which is 100 times more potent than GASP-2, preferentially binds myostatin in an asymmetrical 1:1 complex, whereas GASP-2 binds in a symmetrical 2:1 complex. Additionally, C-terminal truncations of GASP-1 result in less potent myostatin inhibitors that form a 2:1 complex, suggesting that the C-terminal domains of GASP-1 are the primary mediators for asymmetric complex formation. Overall, this study provides a new perspective on TGF-β antagonism, where closely related antagonists can utilize different ligand-binding strategies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Alternative Binding Modes Identified for Growth and Differentiation Factor-associated Serum Protein (GASP) Family Antagonism of Myostatin*

    Science.gov (United States)

    Walker, Ryan G.; Angerman, Elizabeth B.; Kattamuri, Chandramohan; Lee, Yun-Sil; Lee, Se-Jin; Thompson, Thomas B.

    2015-01-01

    Myostatin, a member of the TGF-β family of ligands, is a strong negative regulator of muscle growth. As such, it is a prime therapeutic target for muscle wasting disorders. Similar to other TGF-β family ligands, myostatin is neutralized by binding one of a number of structurally diverse antagonists. Included are the antagonists GASP-1 and GASP-2, which are unique in that they specifically antagonize myostatin. However, little is known from a structural standpoint describing the interactions of GASP antagonists with myostatin. Here, we present the First low resolution solution structure of myostatin-free and myostatin-bound states of GASP-1 and GASP-2. Our studies have revealed GASP-1, which is 100 times more potent than GASP-2, preferentially binds myostatin in an asymmetrical 1:1 complex, whereas GASP-2 binds in a symmetrical 2:1 complex. Additionally, C-terminal truncations of GASP-1 result in less potent myostatin inhibitors that form a 2:1 complex, suggesting that the C-terminal domains of GASP-1 are the primary mediators for asymmetric complex formation. Overall, this study provides a new perspective on TGF-β antagonism, where closely related antagonists can utilize different ligand-binding strategies. PMID:25657005

  11. Neuropeptide Y Y5 receptor antagonism causes faster extinction and attenuates reinstatement in cocaine-induced place preference

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Wörtwein, Gitta; Fink-Jensen, Anders

    2013-01-01

    Several studies have suggested a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. Recently, our group showed a role for the NPY Y5 receptor in the modulation of acute reinforcing effects of cocaine using self-administration and hyperlocomotion paradigms. In the pre......Several studies have suggested a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. Recently, our group showed a role for the NPY Y5 receptor in the modulation of acute reinforcing effects of cocaine using self-administration and hyperlocomotion paradigms....... In the present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence......, and reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance...

  12. Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

    Science.gov (United States)

    Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

    2018-03-23

    During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Baseline characteristics in PRIORITY study: Proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in type 2 diabetes

    DEFF Research Database (Denmark)

    Tofte, Nete

    diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria) trial, the aim is to confirm that CKD273 can predict microalbuminuria prospectively, and to test whether mineralocorticoid receptor antagonism (MRA) delays progression to microalbuminuria. Here we report the association between CKD273...... and traditional risk factors for diabetic nephropathy at baseline. Materials and methods PRIORITY is an investigator-initiated, prospective, randomized, double blind, placebo-controlled multicentre clinical trial and observational study in normoalbuminuric type 2 diabetic patients. Patients are stratified...... is development of microalbuminuria. Results In total 2277 type 2 diabetic patients have been screened over a time period of 2.5 years and 1811 are included from 15 sites. Table 1 shows the baseline characteristics. 224 (12.4%) have the high-risk CKD273 pattern. The high- and low-risk populations differ...

  14. The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism

    DEFF Research Database (Denmark)

    Jørgensen, Malene; Olsen, Christian A; Mellor, Ian R

    2005-01-01

    , establishing general protocols for philanthotoxin solution- and solid-phase synthesis (39-90% and 42-54% overall yields, respectively). The analogues were tested for their ability to antagonize kainate-induced currents of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazoyl)propanoic acid receptors (AMPAR) expressed...... in Xenopus oocytes from rat brain mRNA. This showed that steric bulk in the amino acid moiety is well tolerated and suggests that binding to AMPAR does not involve the alpha-NHCO group as a donor in hydrogen bonding.......Philanthotoxin-343 (PhTX-343), a synthetic analogue of wasp toxin PhTX-433, is a noncompetitive antagonist at ionotropic receptors (e.g., AChR or iGluR). To determine possible effects of variations of the amino acid side chain, a library consisting of seventeen PhTX-343 analogues was prepared. Thus...

  15. Three New Soil-inhabiting Species of Trichoderma in the Stromaticum Clade with Test of Their Antagonism to Pathogens.

    Science.gov (United States)

    Chen, Kai; Zhuang, Wen-Ying

    2017-09-01

    Trichoderma is a dominant component of the soil mycoflora. During the field investigations of northern, central, and southwestern China, three new species in the Stromaticum clade were encountered from soil, and named as T. hebeiense, T. sichuanense, and T. verticillatum. Their phylogenetic positions were determined by analyses of the combined two genes: partial sequences of translation elongation factor 1-alpha and the second largest RNA polymerase subunit-encoding genes. Distinctions between the new species and their close relatives were discussed. Trichoderma hebeiense appeared as a separate terminal branch. The species is distinctive by its oblong conidia and aggregated pustules in culture. Trichoderma sichuanense features in concentric colony and produces numerous clean exudates on aerial mycelium in culture. Trichoderma verticillatum is characterized by its verticillium-like synanamorph and production of abundant chlamydospores. In vitro antagonism towards the new species was tested by dual culture technique.

  16. Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

    International Nuclear Information System (INIS)

    Hennies, H.H.; Hess, V.; Flohe, L.

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

  17. Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Hennies, H H; Hess, V; Flohe, L

    1984-01-01

    Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

  18. SSX2 is a novel DNA-binding protein that antagonizes polycomb group body formation and gene repression

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Relster, Mette Marie; Greve, Katrine Buch Viden

    2014-01-01

    Polycomb group (PcG) complexes regulate cellular identity through epigenetic programming of chromatin. Here, we show that SSX2, a germline-specific protein ectopically expressed in melanoma and other types of human cancers, is a chromatin-associated protein that antagonizes BMI1 and EZH2 PcG body...... formation and derepresses PcG target genes. SSX2 further negatively regulates the level of the PcG-associated histone mark H3K27me3 in melanoma cells, and there is a clear inverse correlation between SSX2/3 expression and H3K27me3 in spermatogenesis. However, SSX2 does not affect the overall composition...

  19. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Uller, Lena; Mathiesen, Jesper Mosolff; Alenmyr, Lisa

    2007-01-01

    BACKGROUND: Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells......, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist...... in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model. RESULTS: TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other...

  20. Antagonism of the Phosphatase PP1 by the Measles Virus V Protein Is Required for Innate Immune Escape of MDA5

    NARCIS (Netherlands)

    Davis, Meredith E.; Wang, May K.; Rennick, Linda J.; Full, Florian; Gableske, Sebastian; Mesman, Annelies W.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.; Duprex, W. Paul; Gack, Michaela U.

    2014-01-01

    The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the

  1. Analogues of neuroactive polyamine wasp toxins that lack inner basic sites exhibit enhanced antagonism toward a muscle-type mammalian nicotinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Stromgaard, K; Brierley, M J; Andersen, K

    1999-01-01

    noncompetitively antagonized the nicotinic acetylcholine receptor (nAChR) in a concentration-, time-, and voltage-dependent manner. The amplitudes of acetylcholine-induced currents were compared at their peaks and at the end of a 1 s application in the presence or absence of the analogues. Most of the analogues...

  2. Draft Genome Sequence of Streptomyces sp. Strain Wb2n-11, a Desert Isolate with Broad-Spectrum Antagonism against Soilborne Phytopathogens

    Energy Technology Data Exchange (ETDEWEB)

    Köberl, Martina; White, Richard A.; Erschen, Sabine; El-Arabi, Tarek F.; Jansson, Janet K.; Berg, Gabriele

    2015-08-06

    Streptomyces sp. strain Wb2n-11, isolated from native desert soil, exhibited broad-spectrum antagonism against plant pathogenic fungi, bacteria and nematodes. The 8.2 Mb draft genome reveals genes putatively responsible for its promising biocontrol activity and genes which enable the soil bacterium to directly interact beneficially with plants.

  3. [Antagonism between hospital strains of Staphylococcus aureus and lactic acid bacteria in vitro and the use of the latter as a sanitary agent].

    Science.gov (United States)

    Ambartsumian, A D; Dekhtsunian, K M; Atopek, S Ia; Erzinkian, L A

    1983-08-01

    The study of antagonism between S. aureus hospital strains and lactic acid bacteria, strain 317/402 "Nariné", revealed that the latter possessed high antagonistic activity. A new method for the sanitation of carriers of S. aureus hospital strains was developed; this method made it possible to limit the epidemiological significance of 82% of these strains.

  4. Unsurmountable antagonism of brain 5-hydroxytryptamine2 receptors by (+)-lysergic acid diethylamide and bromo-lysergic acid diethylamide.

    Science.gov (United States)

    Burris, K D; Sanders-Bush, E

    1992-11-01

    Lysergic acid diethylamide (LSD) and its structural analogue 2-bromo-lysergic acid diethylamide (BOL) act as unsurmountable antagonists of serotonin-elicited contractions in smooth muscle preparations. Two different models, allosteric and kinetic, have been invoked to explain these findings. The present studies investigate the mechanism of antagonism of brain 5-hydroxytryptamine (5HT)2 receptors, utilizing cells transfected with 5HT2 receptor cDNA cloned from rat brain. A proximal cellular response, phosphoinositide hydrolysis, was examined in order to minimize possible postreceptor effects. Even though LSD behaved as a partial agonist and BOL as a pure antagonist, both drugs blocked the effect of serotonin in an unsurmountable manner, i.e., increasing concentrations of serotonin could not overcome the blocking effect of LSD or BOL. Radioligand binding studies showed that preincubation of membranes with either LSD or BOL reduced the density of [3H]ketanserin binding sites, suggesting that the drugs bind tightly to the 5HT2 receptor and are not displaced during the binding assay. Two additional experiments supported this hypothesis. First, the off-rate of [3H] LSD was slow (20 min), relative to that of [3H]ketanserin (approximately 4 min). Second, when the length of incubation with [3H]ketanserin was increased to 60 min, the LSD-induced decrease in Bmax was essentially eliminated. The possibility that LSD and BOL decrease [3H]ketanserin binding by interacting with an allosteric site was rejected, because neither drug altered the rate of dissociation of [3H]ketanserin. The most parsimonious interpretation of these results is that unsurmountable antagonism reflects prolonged occupancy of the receptor by slowly reversible antagonists.

  5. Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: a randomized controlled study.

    Science.gov (United States)

    Abdulatif, Mohamed; Lotfy, Maha; Mousa, Mahmoud; Afifi, Mohamed H; Yassen, Khaled

    2018-02-05

    This randomized controlled study compared the recovery times of sugammadex and neostigmine as antagonists of moderate rocuroniuminduced neuromuscular block in patients with liver cirrhosis and controls undergoing liver resection. The study enrolled 27 adult patients with Child class "A" liver cirrhosis and 28 patients with normal liver functions. Normal patients and patients with liver cirrhosis were randomized according to the type of antagonist (sugammadex 2mg/kg or neostigmine 50μg/kg). The primary outcome was the time from antagonist administration to a trainoffour (TOF) ratio of 0.9 using mechanosensor neuromuscular transmission module. The durations of the intubating and topup doses of rocuronium, the length of stay in the postanesthesia care unit (PACU), and the incidence of postoperative re curarization were recorded. The durations of the intubating and topup doses of rocuronium were prolonged in patients with liver cirrhosis than controls. The times to a TOF ratio of 0.9 were 3.1 (1.0) and 2.6 (1.0) min after sugammadex administration in patients with liver cirrhosis and controls, respectively, p=1.00. The corresponding times after neostigmine administration were longer than sugammadex 14.5 (3.6) and 15.7 (3.6) min, respectively, psugammadex compared to neostigmine. We did not encounter postoperative recurarization after sugammadex or neostigmine. Sugammadex rapidly antagonize moderate residual rocuronium induced neuromuscular block in patients with Child class "A" liver cirrhosis undergoing liver resection. Sugammadex antagonism is associated with 80% reduction in the time to adequate neuromuscular recovery compared to neostigmine.

  6. Detection of Fusarium spp. and Trichoderma spp. and antagonism of Trichoderma sp. in soybean under no-tillage

    Directory of Open Access Journals (Sweden)

    Paola Mendes Milanesi

    2013-12-01

    Full Text Available This study aimed i to quantify the occurrence of Fusarium spp. and Trichoderma spp. in rhizospheric soil, with and without symptoms of Sudden Death Syndrome (SDS in eight soybean genotypes; ii morphologically identify isolates of Fusarium spp. from roots with SDS; iii evaluate the antagonism between Trichoderma spp. and Fusarium spp. isolates from rhizospheric soil and roots from with and without SDS, respectively; and iv characterize through the ITS1-5.8S-ITS2 region of rDNA the isolates of Trichoderma spp. with better performance in the direct confrontation. The sampling of soil and roots was performed in an experimental area located in Cruz Alta, RS, Brazil. In the laboratory, serial dilutions of soil samples, counting of the number of Colony Forming Units (UFCs/g-1 of rhizospheric soil were performed as well as isolation for identification of isolates of Fusarium spp. and Trichoderma spp. and testing of direct confrontation. There were significant differences between the population of Trichoderma spp. in the rhizosphere of plants with and without symptoms of SDS. For the population of Fusarium spp., significant difference was observed only in the rhizosphere of plants without symptoms of SDS. In diseased roots the following species were identified: F. solani, F. avenaceum, F. graminearum, F. oxysporum and F. verticillioides. In the test of direct confrontation, eight isolates of Trichoderma spp. achieved the best performance in the antagonism to Fusarium spp. and Trichoderma spp. from areas with symptoms of SDS had a higher control efficiency in vitro. These isolates showed high similarity to the species of T. koningii agregate.

  7. The Effect of Active Principles of Cilantro and Spirulina Powder on Lead Antagonism to Copper and Chromium in Carassius gibelio

    Directory of Open Access Journals (Sweden)

    Mărioara Nicula

    2017-11-01

    Full Text Available The goal of our work was to highlight the detoxifying potential of the active principles from lyophilized cilantro and spirulina in experimental contamination with lead, to Carassius gibelio, and their effect on lead antagonism to copper and chromium. 120 Prussian carps, weighing 22-25 g each were divided according to the following treatments for 21 days: C group (without treatment, E1 group (75 ppm Pb into water as Pb(NO32x ½H2O, E2 group (75 ppm Pb into water+2% lyophilized cilantro in feed, E3 group (75 ppm Pb into water+2% lyophilized spirulina in feed. At the end of the experimental period, tissue samples (gills, muscles myotome– epaxial, heart, skin and scales, intestine, liver, brain, gonads, kidney were collected after a starving for 12 hours, and fish euthanasia with clove oil. Determination of Cu and Cr concentration in biological samples was performed using atomic absorption spectrophotometer AAS-VARIAN. Pb addition into water in dose of 75 ppm, has resulted in Cu and Cr mobilization from fish tissues. Decreasing of Cu tissue level occurred less intensive in tissues sampled from groups receiving cilantro and spiriulina powder in feed, maximum efficiency in the counteracting the antagonism against Pb showing spirulina on the heart, liver, and kidney. Cr was maintained at relatively low values, although, cilantro powder has induced in some wise the Pb complexing. In contrast, the freeze-dried spirulina brought the tissue level of Cr close to that of the control group or even has determined its more efficient takeover from the feed.

  8. Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

    International Nuclear Information System (INIS)

    Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.; Ertel, P.J.; Bemis, K.G.; Robertson, D.W.

    1991-01-01

    Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09 microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas

  9. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    Directory of Open Access Journals (Sweden)

    Högberg Thomas

    2007-02-01

    Full Text Available Abstract Background Mast cell-derived prostaglandin D2 (PGD2, may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2, a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology. Methods Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model. Results TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. Conclusion This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.

  10. The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies.

    Science.gov (United States)

    Brinkmann, Constantin; Nehlmeier, Inga; Walendy-Gnirß, Kerstin; Nehls, Julia; González Hernández, Mariana; Hoffmann, Markus; Qiu, Xiangguo; Takada, Ayato; Schindler, Michael; Pöhlmann, Stefan

    2016-12-15

    The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism. Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The

  11. Mixed Beam Murine Harderian Gland Tumorigenesis: Predicted Dose-Effect Relationships if neither Synergism nor Antagonism Occurs

    Energy Technology Data Exchange (ETDEWEB)

    Siranart, Nopphon; Blakely, Eleanor A.; Cheng, Alden; Handa, Naval; Sachs, Rainer K.

    2016-12-01

    Complex mixed radiation fields exist in interplanetary space, and not much is known about their latent effects on space travelers. In silico synergy analysis default predictions are useful when planning relevant mixed-ion-beam experiments and interpreting their results. These predictions are based on individual dose-effect relationships (IDER) for each component of the mixed-ion beam, assuming no synergy or antagonism. For example, a default hypothesis of simple effect additivity has often been used throughout the study of biology. However, for more than a century pharmacologists interested in mixtures of therapeutic drugs have analyzed conceptual, mathematical and practical questions similar to those that arise when analyzing mixed radiation fields, and have shown that simple effect additivity often gives unreasonable predictions when the IDER are curvilinear. Various alternatives to simple effect additivity proposed in radiobiology, pharmacometrics, toxicology and other fields are also known to have important limitations. In this work, we analyze upcoming murine Harderian gland (HG) tumor prevalence mixed-beam experiments, using customized open-source software and published IDER from past single-ion experiments. The upcoming experiments will use acute irradiation and the mixed beam will include components of high atomic number and energy (HZE). We introduce a new alternative to simple effect additivity, "incremental effect additivity", which is more suitable for the HG analysis and perhaps for other end points. We use incremental effect additivity to calculate default predictions for mixture dose-effect relationships, including 95% confidence intervals. We have drawn three main conclusions from this work. 1. It is important to supplement mixed-beam experiments with single-ion experiments, with matching end point(s), shielding and dose timing. 2. For HG tumorigenesis due to a mixed beam, simple effect additivity and incremental effect additivity sometimes give

  12. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

    Science.gov (United States)

    Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

    2013-12-01

    Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

  13. Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.

    Science.gov (United States)

    Wang, De-Shen; Patel, Atish; Shukla, Suneet; Zhang, Yun-Kai; Wang, Yi-Jun; Kathawala, Rishil J; Robey, Robert W; Zhang, Li; Yang, Dong-Hua; Talele, Tanaji T; Bates, Susan E; Ambudkar, Suresh V; Xu, Rui-Hua; Chen, Zhe-Sheng

    2014-06-30

    ABCG2 is a potential biomarker causing multidrug resistance (MDR) in Non-Small Cell Lung Cancer (NSCLC). We conducted this study to investigate whether Icotinib, a small-molecule inhibitor of EGFR tyrosine kinase, could interact with ABCG2 transporter in NSCLC. Our results showed that Icotinib reversed ABCG2-mediated MDR by antagonizing the drug efflux function of ABCG2. Icotinib stimulated the ATPase activity in a concentration-dependent manner and inhibited the photolabeling of ABCG2 with [125I]-Iodoarylazidoprazosin, demonstrating that it interacts at the drug-binding pocket. Homology modeling predicted the binding conformation of Icotinib at Asn629 centroid-based grid of ABCG2. However, Icotinib at reversal concentration did not affect the expression levels of AKT and ABCG2. Furthermore, a combination of Icotinib and topotecan exhibited significant synergistic anticancer activity against NCI-H460/MX20 tumor xenografts. However, the inhibition of transport activity of ABCG2 was insufficient to overcome pemetrexed resistance in NCI-H460/MX20 cells, which was due to the co-upregulated thymidylate synthase (TS) and ABCG2 expression. This is the first report to show that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate. Our findings suggested different possible strategies of overcoming the resistance of topotecan and pemetrexed in the NSCLC patients.

  14. Antagonizing SET augments the effects of radiotherapy in hepatocellular carcinoma through reactivating PP2A-mediated AKT downregulation.

    Science.gov (United States)

    Huang, Chao-Yuan; Hung, Man-Hsin; Shih, Chi-Ting; Hsieh, Feng-Shu; Kuo, Chiung-Wen; Tsai, Ming-Hsien; Chang, Shih-Shin; Hsiao, Yung-Jen; Chen, Li-Ju; Chao, Tzu-I; Chen, Kuen-Feng

    2018-06-18

    Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiotherapy (RT)-mediated anti-cancer effects has not yet been explored. Here, we investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assay, we found that RT-induced proliferative inhibition was critically associated with SET expression. Next, we tested a novel SET antagonist, EMQA, in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared to mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore PP2A-mediated p-AKT downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET, and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach. The American Society for Pharmacology and Experimental Therapeutics.

  15. Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS.

    Science.gov (United States)

    Zhang, Guigen; Chan, Baca; Samarina, Naira; Abere, Bizunesh; Weidner-Glunde, Magdalena; Buch, Anna; Pich, Andreas; Brinkmann, Melanie M; Schulz, Thomas F

    2016-02-23

    The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.

  16. Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses.

    Science.gov (United States)

    de Torres Zabala, Marta; Bennett, Mark H; Truman, William H; Grant, Murray R

    2009-08-01

    The importance of phytohormone balance is increasingly recognized as central to the outcome of plant-pathogen interactions. Recently it has been demonstrated that abscisic acid signalling pathways are utilized by the bacterial phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we examined the dynamics, inter-relationship and impact of three key acidic phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial virulence factor, coronatine, during progression of P. syringae infection of Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to play important early roles in determining the outcome of the infection process. SA is required in order to mount a full innate immune responses, while bacterial effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible innate immune responses by down-regulating SA biosynthesis and SA-mediated defences. Mutant analyses indicated that endogenous ABA levels represent an important reservoir that is necessary for effector suppression of plant-inducible innate defence responses and SA synthesis prior to subsequent pathogen-induced increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal resistance is epistatically dominant over acquired resistance due to ABA deficiency, although ABA also contributes to symptom development. We conclude that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences. We predict that hormonal perturbations, either induced or as a result of environmental stress, have a marked impact on pathological outcomes, and we provide a mechanistic basis for understanding priming events in plant defence.

  17. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

    Science.gov (United States)

    Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

    2007-12-01

    Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

  18. Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

    Science.gov (United States)

    Vidal, Marcos; Ramana, Chilakamarti V.; Dusso, Adriana S.

    2002-01-01

    The cytokine gamma interferon (IFN-γ) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-γ induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-γ-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-γ and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-γ action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-γ/Stat1-induced transcription. This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties. PMID:11909970

  19. Rce1, a novel transcriptional repressor, regulates cellulase gene expression by antagonizing the transactivator Xyr1 in Trichoderma reesei.

    Science.gov (United States)

    Cao, Yanli; Zheng, Fanglin; Wang, Lei; Zhao, Guolei; Chen, Guanjun; Zhang, Weixin; Liu, Weifeng

    2017-07-01

    Cellulase gene expression in the model cellulolytic fungus Trichoderma reesei is supposed to be controlled by an intricate regulatory network involving multiple transcription factors. Here, we identified a novel transcriptional repressor of cellulase gene expression, Rce1. Disruption of the rce1 gene not only facilitated the induced expression of cellulase genes but also led to a significant delay in terminating the induction process. However, Rce1 did not participate in Cre1-mediated catabolite repression. Electrophoretic mobility shift (EMSA) and DNase I footprinting assays in combination with chromatin immunoprecipitation (ChIP) demonstrated that Rce1 could bind directly to a cbh1 (cellobiohydrolase 1-encoding) gene promoter region containing a cluster of Xyr1 binding sites. Furthermore, competitive binding assays revealed that Rce1 antagonized Xyr1 from binding to the cbh1 promoter. These results indicate that intricate interactions exist between a variety of transcription factors to ensure tight and energy-efficient regulation of cellulase gene expression in T. reesei. This study also provides important clues regarding increased cellulase production in T. reesei. © 2017 John Wiley & Sons Ltd.

  20. A novel TNFα antagonizing peptide-Fc fusion protein designed based on CDRs of TNFα neutralizing monoclonal antibody

    International Nuclear Information System (INIS)

    Qin Weisong; Feng Jiannan; Zhang Wei; Li Yan; Shen, Beifen

    2004-01-01

    The variable regions of antibody molecules bind antigens with high affinity and specificity. The binding sites are imparted largely to the hypervariable portions (i.e., CDRs) of the variable region. Peptides derived from CDRs can bind antigen with similar specificity acting as mimic of antibody and become drug-designing core, although with markedly lower affinity. In order to increase the affinity and bioactivity, in this study, a novel peptide (PT) designed on CDRs of a TNFα neutralizing monoclonal antibody Z12 was linked with Fc fragment of human IgG1. The interaction mode of PT-linker-Fc (PLF) with TNFα was analyzed with computer-guided molecular modeling method. After expression in Escherichia coli and purification, recombinant PT-linker-Fc could bind directly with the TNFα coated on the ELISA plates. Furthermore, PLF could competitively inhibit the binding of Z12 to TNFα and also inhibit the TNFα-induced cytotoxicity on L929 cells. The TNFα antagonizing activity of PLF was significantly higher than that of the free peptide. This study highlights the potential of human Fc to enhance the potency of peptides designed on the CDRs of antibodies and could be useful in developing new TNFα antagonists

  1. Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations.

    Science.gov (United States)

    Flores, África; Herry, Cyril; Maldonado, Rafael; Berrendero, Fernando

    2017-08-01

    Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated. We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation. Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala. These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867. © The Author 2017. Published by Oxford University Press on behalf of CINP.

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

    Science.gov (United States)

    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.

  3. Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations.

    Directory of Open Access Journals (Sweden)

    Hsin-Hung Chou

    2014-02-01

    Full Text Available How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncover the fitness landscape defined by gene expression levels. We found strong antagonism and sign epistasis between these beneficial mutations. Mutations with the largest individual benefit interacted the most antagonistically with other mutations, a trend we also uncovered through analyses of datasets from other model systems. However, these beneficial mutations interacted multiplicatively (i.e., no epistasis at the level of enzyme expression. By generating a model that predicts fitness from enzyme levels we could explain the observed sign epistasis as a result of overshooting the optimum defined by a balance between enzyme catalysis benefits and fitness costs. Knowledge of the phenotypic landscape also illuminated that, although the fitness peak was phenotypically far from the ancestral state, it was not genetically distant. Single beneficial mutations jumped straight toward the global optimum rather than being constrained to change the expression phenotypes in the correlated fashion expected by the genetic architecture. Given that adaptation in nature often results from optimizing gene expression, these conclusions can be widely applicable to other organisms and selective conditions. Poor interactions between individually beneficial alleles affecting gene expression may thus compromise the benefit of sex during adaptation and promote genetic differentiation.

  4. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism.

    Science.gov (United States)

    Song, Ju-Xian; Choi, Mandy Yuen-Man; Wong, Kavin Chun-Kit; Chung, Winkie Wing-Yan; Sze, Stephen Cho-Wing; Ng, Tzi-Bun; Zhang, Kalin Yan-Bo

    2012-01-21

    Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism. Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots. Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2. The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.

  5. Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

    Directory of Open Access Journals (Sweden)

    Song Ju-Xian

    2012-01-01

    Full Text Available Abstract Background Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism. Methods Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS and loss of mitochondrial membrane potential (ΔΨm were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots. Results Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2. Conclusion The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.

  6. Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome.

    Science.gov (United States)

    Luthra, Priya; Ramanan, Parameshwaran; Mire, Chad E; Weisend, Carla; Tsuda, Yoshimi; Yen, Benjamin; Liu, Gai; Leung, Daisy W; Geisbert, Thomas W; Ebihara, Hideki; Amarasinghe, Gaya K; Basler, Christopher F

    2013-07-17

    The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line.

    Science.gov (United States)

    Viall, A K; Goodall, C P; Stang, B; Marley, K; Chappell, P E; Bracha, S

    2016-06-01

    Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target. © 2014 John Wiley & Sons Ltd.

  8. Potential antagonism of some Trichoderma strains isolated from Moroccan soil against three phytopathogenic fungi of great economic importance

    Directory of Open Access Journals (Sweden)

    Wafaa MOKHTARI

    2017-09-01

    Full Text Available In this study, 17 Trichoderma strains were isolated from different soils (crop fields and Argan forests in Morocco. Purified monospore cultures were identified using molecular methods and tested for their potential antagonism against three phytopathogenic fungi (Fusarium oxyxporum, verticillium dahlia and rhizoctonia solani. After DNA extraction, translation elongation factor (tef1 was amplified in extracts of 17 strains, sequenced and compared with their ex-types. As a result, three species were identified among the strains, which clustered in two different subclades of Trichoderma: the species T. afroharzianum, and T. guizhouense belong to the Harzianum clade, while T. longibrachiatum belongs to the Longibrachiatum clade. Investigation of potential antagonistic effects of these strains against the soil-borne phytopathogens F. oxysporum, R. solani and V. dahliae was conducted in a dual culture plate assay, using 17 promising Trichoderma strains that have been selected based on a polymerase chain reaction (PCR screening approach. In vitro, Trichoderma isolates showed effective antagonistic performance by decreasing soil borne pathogens mycelium radial growth. Trichoderma afroharzianum showed the highest Percentage of Radial Inhibition Growth (PRIG %. The highest PRIG% = 98% was for 8A2.3 isolate against R. solani and the lowest PRIG%= 67% for T9i10 against F. oxysporum. On the other hand, T9i12, which is T. reesei species, led to a high radial inhibition of pathogens’ mycelium.

  9. Antagonism of botulinum toxin-induced muscle weakness by aminopyridines in rat phrenic nerve-hemidiaphragm preparations

    Energy Technology Data Exchange (ETDEWEB)

    Adler, M.; Scovill, J.; Deshpande, S.S.

    1993-05-13

    The effects of the potassium channel inhibitor and putative botulinum toxin antagonists 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile and electrophysiological properties of rat diaphragm muscle. In the presence of 300 pM botulinum toxin A (BoTx A), twitches elicited by supramaximal nerve stimulation (0. 1 Hz) were reduced by over 80% in 3 hr. The time to block decreased with increases in temperature, toxin concentration and stimulation frequency. Addition of 4-AP or 3,4-DAP led to a prompt reversal of the BoTx A-induced depression of twitch tension. This reversal was concentration-dependent such that, in the presence of 1 mM 4-AP, reversal of the BoTx A-induced blockade was complete in 6.7 min. The beneficial effect of the APs were well maintained and persisted for up to 6 hr after addition. Application of 1 microns M neostigmine 1 hr after 3,4-DAP produced a further potentiation of twitch tensions, but this action lasted for < 5 min and led to the appearance of tetanic fade during repetitive stimulation. It is concluded that the APs are of benefit in antagonizing the muscle paralysis following exposure to botulinum toxin. Co-application of neostigmine, however, appears to confer no additional benefit.

  10. Isobolographic Analysis for Additive, Synergism and Antagonism Effects in Binary Mixture of Mesosulfuron + Iodosulfuron and Clodinafop-Propargyl

    Directory of Open Access Journals (Sweden)

    A. A Chitband

    2012-07-01

    Full Text Available The reduction of herbicide applications is a main research priority in recent years for herbicide reducing the risk of side-effects and costs from herbicides. Therefore To predicting additive, synergism or antagonism effects mesosulfuron + iodosulfuron and clodinafop-propargyl two herbicides mixture on wild oat with isobole curvatures, greenhouse experimental in completely randomized design with 36 treatments (in dose-response arrangements and four replicates for each experiment treatments were conducted at Ferdowsi University of Mashhad. Treatments included mesosulfuron + iodosulfuron alone at doses of 0 , 2.4, 6, 12, 18 and 24 g ai ha-1, clodinafop alone at doses of 0, 6.4, 16, 32, 48 and 64 g ai ha-1 and six mixtures ratio of doses of two herbicides above mentioned as 100:0%,75:25%, 50:50%, 25:75% , 10:90% and 0:100%. The results showed mesosulfuron + iodosulfuron and clodinafop-propargyl at high dose rates showed complete control of wild oat. In addition Concentration Addition (CA model describe Fitted the data better than Hewlett and Voelund models. On the other hand, herbicides combination with each other showed additive effects on wild oat control, As by increasing the clodinafop-propargyl ratio in mixtures (90% clodinafop-propargyl + 10% mesosulfuron + iodosulfuron increased wild oat control compared with other mixing ratios remarkably.

  11. The elongin complex antagonizes the chromatin factor Corto for vein versus intervein cell identity in Drosophila wings.

    Science.gov (United States)

    Rougeot, Julien; Renard, Myrtille; Randsholt, Neel B; Peronnet, Frédérique; Mouchel-Vielh, Emmanuèle

    2013-01-01

    Drosophila wings mainly consist of two cell types, vein and intervein cells. Acquisition of either fate depends on specific expression of genes that are controlled by several signaling pathways. The nuclear mechanisms that translate signaling into regulation of gene expression are not completely understood, but they involve chromatin factors from the Trithorax (TrxG) and Enhancers of Trithorax and Polycomb (ETP) families. One of these is the ETP Corto that participates in intervein fate through interaction with the Drosophila EGF Receptor--MAP kinase ERK pathway. Precise mechanisms and molecular targets of Corto in this process are not known. We show here that Corto interacts with the Elongin transcription elongation complex. This complex, that consists of three subunits (Elongin A, B, C), increases RNA polymerase II elongation rate in vitro by suppressing transient pausing. Analysis of phenotypes induced by EloA, B, or C deregulation as well as genetic interactions suggest that the Elongin complex might participate in vein vs intervein specification, and antagonizes corto as well as several TrxG genes in this process. Chromatin immunoprecipitation experiments indicate that Elongin C and Corto bind the vein-promoting gene rhomboid in wing imaginal discs. We propose that Corto and the Elongin complex participate together in vein vs intervein fate, possibly through tissue-specific transcriptional regulation of rhomboid.

  12. The elongin complex antagonizes the chromatin factor Corto for vein versus intervein cell identity in Drosophila wings.

    Directory of Open Access Journals (Sweden)

    Julien Rougeot

    Full Text Available Drosophila wings mainly consist of two cell types, vein and intervein cells. Acquisition of either fate depends on specific expression of genes that are controlled by several signaling pathways. The nuclear mechanisms that translate signaling into regulation of gene expression are not completely understood, but they involve chromatin factors from the Trithorax (TrxG and Enhancers of Trithorax and Polycomb (ETP families. One of these is the ETP Corto that participates in intervein fate through interaction with the Drosophila EGF Receptor--MAP kinase ERK pathway. Precise mechanisms and molecular targets of Corto in this process are not known. We show here that Corto interacts with the Elongin transcription elongation complex. This complex, that consists of three subunits (Elongin A, B, C, increases RNA polymerase II elongation rate in vitro by suppressing transient pausing. Analysis of phenotypes induced by EloA, B, or C deregulation as well as genetic interactions suggest that the Elongin complex might participate in vein vs intervein specification, and antagonizes corto as well as several TrxG genes in this process. Chromatin immunoprecipitation experiments indicate that Elongin C and Corto bind the vein-promoting gene rhomboid in wing imaginal discs. We propose that Corto and the Elongin complex participate together in vein vs intervein fate, possibly through tissue-specific transcriptional regulation of rhomboid.

  13. Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

    Science.gov (United States)

    Lalanne, L; Ayranci, G; Filliol, D; Gavériaux-Ruff, C; Befort, K; Kieffer, B L; Lutz, P-E

    2017-07-01

    Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals. © 2016 Society for the Study of Addiction.

  14. Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing

    Science.gov (United States)

    Tie, Feng; Banerjee, Rakhee; Saiakhova, Alina R.; Howard, Benny; Monteith, Kelsey E.; Scacheri, Peter C.; Cosgrove, Michael S.; Harte, Peter J.

    2014-01-01

    Trithorax (TRX) antagonizes epigenetic silencing by Polycomb group (PcG) proteins, stimulates enhancer-dependent transcription, and establishes a ‘cellular memory’ of active transcription of PcG-regulated genes. The mechanisms underlying these TRX functions remain largely unknown, but are presumed to involve its histone H3K4 methyltransferase activity. We report that the SET domains of TRX and TRX-related (TRR) have robust histone H3K4 monomethyltransferase activity in vitro and that Tyr3701 of TRX and Tyr2404 of TRR prevent them from being trimethyltransferases. The trxZ11 missense mutation (G3601S), which abolishes H3K4 methyltransferase activity in vitro, reduces the H3K4me1 but not the H3K4me3 level in vivo. trxZ11 also suppresses the impaired silencing phenotypes of the Pc3 mutant, suggesting that H3K4me1 is involved in antagonizing Polycomb silencing. Polycomb silencing is also antagonized by TRX-dependent H3K27 acetylation by CREB-binding protein (CBP). We show that perturbation of Polycomb silencing by TRX overexpression requires CBP. We also show that TRX and TRR are each physically associated with CBP in vivo, that TRX binds directly to the CBP KIX domain, and that the chromatin binding patterns of TRX and TRR are highly correlated with CBP and H3K4me1 genome-wide. In vitro acetylation of H3K27 by CBP is enhanced on K4me1-containing H3 substrates, and independently altering the H3K4me1 level in vivo, via the H3K4 demethylase LSD1, produces concordant changes in H3K27ac. These data indicate that the catalytic activities of TRX and CBP are physically coupled and suggest that both activities play roles in antagonizing Polycomb silencing, stimulating enhancer activity and cellular memory. PMID:24550119

  15. Quantification of the uncertainties in extrapolating from in vitro androgen receptor (AR) antagonism to key events in in vivo screening assays and adverse reproductive outcomes in F1 male rats

    Science.gov (United States)

    There are multiple molecular initiating events (MIEs) that can disrupt male sexual differentiation including AR antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of this event by pesticides like vinclozolin that act as AR antagonists and ph...

  16. A novel ion-beam-mutation effect application in identification of gene involved in bacterial antagonism to fungal infection of ornamental crops

    Energy Technology Data Exchange (ETDEWEB)

    Mahadtanapuk, S. [Faculty of Agriculture and Natural Resources, University of Phayao, Maeka, Muang, Phayao 56000 (Thailand); Teraarusiri, W. [Central Laboratory, University of Phayao, Maeka, Muang, Phayao 56000 (Thailand); Nanakorn, W. [The Crown Property Bureau, 173 Nakhonratchasrima Road, Dusit, Bangkok 10300 (Thailand); Yu, L.D., E-mail: yuld@thep-center.org [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Thongkumkoon, P. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Anuntalabhochai, S., E-mail: soanu.1@gmail.com [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

    2014-05-01

    Highlights: • Ion beam bombardment induced mutation in bacterial B. licheniformis. • A mutant lost antifungal activity. • DNA fingerprint of the mutant was analyzed. • The lost gene was indentified to code for TrxR gene. • TrxR gene from B. licheniformis expressed the flower antagonism to fungi. - Abstract: This work is on a novel application of ion beam effect on biological mutation. Bacillus licheniformis (B. licheniformis) is a common soil bacterium with an antagonistic effect on Curcuma alismatifolia Gagnep. and Chrysanthemum indicum Linn. In an attempt to control fungal diseases of local crops by utilizing B. licheniformis, we carried out gene analysis of the bacterium to understand the bacterial antagonistic mechanism. The bacterial cells were bombarded to induce mutations using nitrogen ion beam. After ion bombardment, DNA analysis revealed that the modified polymorphism fragment present in the wild type was missing in a bacterial mutant which lost the antifungal activity. The fragments conserved in the wild type but lost in the mutant bacteria was identified to code for the thioredoxin reductase (TrxR) gene. The gene analysis showed that the TrxR gene from B. licheniformis had the expression of the antagonism to fungi in a synchronous time evolution with the fungus inhibition when the bacteria were co-cultivated with the fungi. The collective results indicate the TrxR gene responsible for the antagonism of bacteria B. licheniformis to fungal infection.

  17. Antagonizing Effects of Aspartic Acid against Ultraviolet A-Induced Downregulation of the Stemness of Human Adipose Tissue-Derived Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Kwangseon Jung

    Full Text Available Ultraviolet A (UVA irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate effects of aspartic acid on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs. Furthermore, we elucidated the UVA-antagonizing mechanisms of aspartic acid. The results of this study showed that aspartic acid attenuated the UVA-induced reduction of the proliferative potential and stemness of hAMSCs, as evidenced by increased proliferative activity in the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and upregulation of stemness-related genes OCT4, NANOG, and SOX2 in response to the aspartic acid treatment. UVA-induced reduction in the mRNA level of hypoxia-inducible factor (HIF-1α was also significantly recovered by aspartic acid. In addition, the antagonizing effects of aspartic acid against the UVA effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show that aspartic acid improves reduced stemness of hAMSCs induced by UVA and its effects are mediated by upregulation of HIF-1α via the inhibition of PGE2-cAMP signaling. In addition, aspartic acid may be used as an antagonizing agent to mitigate the effects of UVA.

  18. Antagonizing Effects of Aspartic Acid against Ultraviolet A-Induced Downregulation of the Stemness of Human Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Jung, Kwangseon; Cho, Jae Youl; Soh, Young-Jin; Lee, Jienny; Shin, Seoung Woo; Jang, Sunghee; Jung, Eunsun; Kim, Min Hee; Lee, Jongsung

    2015-01-01

    Ultraviolet A (UVA) irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate effects of aspartic acid on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Furthermore, we elucidated the UVA-antagonizing mechanisms of aspartic acid. The results of this study showed that aspartic acid attenuated the UVA-induced reduction of the proliferative potential and stemness of hAMSCs, as evidenced by increased proliferative activity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and upregulation of stemness-related genes OCT4, NANOG, and SOX2 in response to the aspartic acid treatment. UVA-induced reduction in the mRNA level of hypoxia-inducible factor (HIF)-1α was also significantly recovered by aspartic acid. In addition, the antagonizing effects of aspartic acid against the UVA effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show that aspartic acid improves reduced stemness of hAMSCs induced by UVA and its effects are mediated by upregulation of HIF-1α via the inhibition of PGE2-cAMP signaling. In addition, aspartic acid may be used as an antagonizing agent to mitigate the effects of UVA.

  19. A novel ion-beam-mutation effect application in identification of gene involved in bacterial antagonism to fungal infection of ornamental crops

    International Nuclear Information System (INIS)

    Mahadtanapuk, S.; Teraarusiri, W.; Nanakorn, W.; Yu, L.D.; Thongkumkoon, P.; Anuntalabhochai, S.

    2014-01-01

    Highlights: • Ion beam bombardment induced mutation in bacterial B. licheniformis. • A mutant lost antifungal activity. • DNA fingerprint of the mutant was analyzed. • The lost gene was indentified to code for TrxR gene. • TrxR gene from B. licheniformis expressed the flower antagonism to fungi. - Abstract: This work is on a novel application of ion beam effect on biological mutation. Bacillus licheniformis (B. licheniformis) is a common soil bacterium with an antagonistic effect on Curcuma alismatifolia Gagnep. and Chrysanthemum indicum Linn. In an attempt to control fungal diseases of local crops by utilizing B. licheniformis, we carried out gene analysis of the bacterium to understand the bacterial antagonistic mechanism. The bacterial cells were bombarded to induce mutations using nitrogen ion beam. After ion bombardment, DNA analysis revealed that the modified polymorphism fragment present in the wild type was missing in a bacterial mutant which lost the antifungal activity. The fragments conserved in the wild type but lost in the mutant bacteria was identified to code for the thioredoxin reductase (TrxR) gene. The gene analysis showed that the TrxR gene from B. licheniformis had the expression of the antagonism to fungi in a synchronous time evolution with the fungus inhibition when the bacteria were co-cultivated with the fungi. The collective results indicate the TrxR gene responsible for the antagonism of bacteria B. licheniformis to fungal infection

  20. INTERAKSI ANTARA Trichoderma Harzianum, Penicillium SP. DAN Pseudomonas SP. SERTA KAPASITAS ANTAGONISMENYA TERHADAP Phytophthora CapsicilN VITRO*[Interaction Among Trichoderma Harzianum, Penicillium SP., Pseudomonas SP. and Antagonism Capacities Against Phy

    OpenAIRE

    Suharna, Nandang

    2003-01-01

    A preliminary study has been done to know antagonism capacities of three isolates of Trichoderma harzianum, two isolates of Penicillium sp.and one isolate of Pseudomonas sp.against Phytophthora capsici in vitro and interaction among those six antagonists.The highest antagonism capacity possessed by Penicillium sp. KN1, respectively followed by Penicillium sp.KN2,Pseudomonas sp. GH1 and the three T. harzianum isolates. Except for those three T. harzianum isolates, the two Penicillium sp.isolat...

  1. 77 FR 27164 - Butylate, Clethodim, Dichlorvos, Dicofol, Isopropyl Carbanilate, et al.; Proposed Tolerance Actions

    Science.gov (United States)

    2012-05-09

    ... byproducts, except liver; egg; goat, fat; goat, liver; goat, meat; goat, meat byproducts, except liver; hog...; beet, sugar, roots; beet, sugar, tops; egg; cattle, fat; cattle, meat; cattle, meat byproducts; goat, fat; goat, meat; goat, meat byproducts; hog, fat; hog, meat; hog, meat byproducts; horse, fat; horse...

  2. 75 FR 44184 - Aluminum tris(O-ethylphosphonate), Butylate, Chlorethoxyfos, Clethodim, et al.; Proposed...

    Science.gov (United States)

    2010-07-28

    ...: Crop production (NAICS code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code... contamination of food, feed, or food-contact/feed-contact surfaces. Compliance with the tolerance level... Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food...

  3. 77 FR 59120 - Butylate, Clethodim, Dichlorvos, Dicofol, Isopropyl Carbanilate, et al.; Tolerance Actions

    Science.gov (United States)

    2012-09-26

    ... certification for organic farming and food processing), Frutban S.A. (an organic banana farm in Ecuador), DFFI........ 3.0 10/31/16 Egg 0.05 10/31/16 Goat, fat 50.0 10/31/16 Goat, liver 5.0 10/31/16 Goat, meat 3.0 10/31/16 Goat, meat byproducts, except liver....... 3.0 10/31/16 Hog, fat 50.0 10/31/16 Hog, liver 5.0 10...

  4. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

    Science.gov (United States)

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-02-01

    Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner.

  5. Ihh enhances differentiation of CFK-2 chondrocytic cells and antagonizes PTHrP-mediated activation of PKA.

    Science.gov (United States)

    Deckelbaum, Ron A; Chan, George; Miao, Dengshun; Goltzman, David; Karaplis, Andrew C

    2002-07-15

    Indian Hedgehog (Ihh), a member of the hedgehog (HH) family of secreted morphogens, and parathyroid hormone-related peptide (PTHrP) are key regulators of cartilage cell (chondrocyte) differentiation. We have investigated, in vitro, the actions of HH signalling and its possible interplay with PTHrP using rat CFK-2 chondrocytic cells. Markers of chondrocyte differentiation [alkaline phosphatase (ALP) activity, and type II (Col2a1) and type X collagen (Col10a1) expression] were enhanced by overexpression of Ihh or its N-terminal domain (N-Ihh), effects mimicked by exogenous administration of recombinant N-terminal HH peptide. Moreover, a missense mutation mapping to the N-terminal domain of Ihh (W160G) reduces the capacity of N-Ihh to induce differentiation. Prolonged exposure of CFK-2 cells to exogenous N-Shh (5x10(-9) M) in the presence of PTHrP (10(-8) M) or forskolin (10(-7) M) resulted in perturbation of HH-mediated differentiation. In addition, overexpression of a constitutively active form of the PTHrP receptor (PTHR1 H223R) inhibited Ihh-mediated differentiation, implicating activation of protein kinase A (PKA) by PTHR1 as a probable mediator of the antagonistic effects of PTHrP. Conversely, overexpression of Ihh/N-Ihh or exogenous treatment with N-Shh led to dampening of PTHrP-mediated activation of PKA. Taken together, our data suggest that Ihh harbors the capacity to induce rather than inhibit chondrogenic differentiation, that PTHrP antagonizes HH-mediated differentiation through a PKA-dependent mechanism and that HH signalling, in turn, modulates PTHrP action through functional inhibition of signalling by PTHR1 to PKA.

  6. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Elgueta, Daniela; Aymerich, María S; Contreras, Francisco; Montoya, Andro; Celorrio, Marta; Rojo-Bustamante, Estefanía; Riquelme, Eduardo; González, Hugo; Vásquez, Mónica; Franco, Rafael; Pacheco, Rodrigo

    2017-02-01

    Neuroinflammation involves the activation of glial cells, which is associated to the progression of neurodegeneration in Parkinson's disease. Recently, we and other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are completely refractory to neuroinflammation and consequent neurodegeneration associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we examined the therapeutic potential and underlying mechanism of a D3R-selective antagonist, PG01037, in mice intoxicated with a chronic regime of administration of MPTP and probenecid (MPTPp). Biodistribution analysis indicated that intraperitoneally administered PG01037 crosses the blood-brain barrier and reaches the highest concentration in the brain 40 min after the injection. Furthermore, the drug was preferentially distributed to the brain in comparison to the plasma. Treatment of MPTPp-intoxicated mice with PG01037 (30 mg/kg, administrated twice a week for five weeks) attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta, as evaluated by stereological analysis, and the loss of striatal dopaminergic terminals, as determined by densitometric analyses of tyrosine hydroxylase and dopamine transporter immunoreactivities. Accordingly, the treatment resulted in significant improvement of motor performance of injured animals. Interestingly, the therapeutic dose of PG01037 exacerbated astrogliosis and resulted in increased ramification density of microglial cells in the striatum of MPTPp-intoxicated mice. Further analyses suggested that D3R expressed in astrocytes favours a beneficial astrogliosis with anti-inflammatory consequences on microglia. Our findings indicate that D3R-antagonism exerts a therapeutic effect in parkinsonian animals by reducing the loss of dopaminergic neurons in the nigrostriatal pathway, alleviating motor impairments and modifying the pro-inflammatory phenotype of glial cells. Copyright

  7. Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

    Science.gov (United States)

    Chen, Menghao; Li, Xiaojing; Fan, Ruifeng; Cao, Changyu; Yao, Haidong; Xu, Shiwen

    2017-11-01

    The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl 2 , 150mg/kg) and sodium selenite (Na 2 SeO 3 , 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need.  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression.  The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively.  We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  9. Antagonism between the dynein and Ndc80 complexes at kinetochores controls the stability of kinetochore-microtubule attachments during mitosis.

    Science.gov (United States)

    Amin, Mohammed A; McKenney, Richard J; Varma, Dileep

    2018-04-20

    Chromosome alignment and segregation during mitosis require kinetochore-microtubule (kMT) attachments that are mediated by the molecular motor dynein and the kMT-binding complex Ndc80. The Rod-ZW10-Zwilch (RZZ) complex is central to this coordination as it has an important role in dynein recruitment and has recently been reported to have a key function in the regulation of stable kMT attachments in Caenorhabditis elegans besides its role in activating the spindle assembly checkpoint (SAC). However, the mechanism by which these protein complexes control kMT attachments to drive chromosome motility during early mitosis is still unclear. Here, using in vitro total internal reflection fluorescence microscopy, we observed that higher concentrations of Ndc80 inhibited dynein binding to MTs, providing evidence that Ndc80 and dynein antagonize each other's function. High-resolution microscopy and siRNA-mediated functional disruption revealed that severe defects in chromosome alignment induced by depletion of dynein or the dynein adapter Spindly are rescued by codepletion of the RZZ component Rod in human cells. Interestingly, rescue of the chromosome alignment defects was independent of Rod function in SAC activation and was accompanied by a remarkable restoration of stable kMT attachments. Furthermore, the chromosome alignment rescue depended on the plus-end-directed motility of centromere protein E (CENP-E) because cells codepleted of CENP-E, Rod, and dynein could not establish stable kMT attachments or align their chromosomes properly. Our findings support the idea that dynein may control the function of the Ndc80 complex in stabilizing kMT attachments directly by interfering with Ndc80-MT binding or indirectly by controlling the Rod-mediated inhibition of Ndc80. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway.

    Science.gov (United States)

    Jin, Luyuan; Cao, Yu; Yu, Guoxia; Wang, Jinsong; Lin, Xiao; Ge, Lihua; Du, Juan; Wang, Liping; Diao, Shu; Lian, Xiaomeng; Wang, Songlin; Dong, Rui; Shan, Zhaochen

    2017-01-01

    Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear. In this study, we used SCAPs to investigate the underlying mechanisms. SCAPs were isolated from the apical papilla of immature third molars. Western blot and real-time RT-PCR were applied to detect the expression of β-catenin and Wnt target genes. Alizarin Red staining, quantitative calcium analysis, transwell cultures and in vivo transplantation experiments were used to study the osteogenic differentiation potential of SCAPs. SFRP2 inhibited canonical Wnt signaling by enhancing phosphorylation and decreasing the expression of nuclear β-catenin in vitro and in vivo . In addition, the target genes of the Wnt signaling pathway, AXIN2 (axin-related protein 2) and MMP7 (matrix metalloproteinase-7), were downregulated by SFRP2 . WNT1 inhibited the osteogenic differentiation potential of SCAPs. SFRP2 could rescue this WNT1 -impaired osteogenic differentiation potential. The results suggest that SFRP2 could bind to locally present Wnt ligands and alter the balance of intracellular Wnt signaling to antagonize the canonical Wnt pathway in SCAPs. This elucidates the molecular mechanism underlying the SFRP2-mediated directed differentiation of SCAPs and indicates potential target genes for improving dental tissue regeneration.

  11. Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.

    Science.gov (United States)

    Li, S Y; Li, X F; Hu, M H; Shao, B; Poston, L; Lightman, S L; O'Byrne, K T

    2014-08-01

    The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling with respect to controlling puberty onset. The present study aimed to determine the role of endogenous NKB-NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion and the timing of puberty onset, and also whether precocious pubertal onset as a result of an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with i.c.v. cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus (as markers of puberty) compared to controls in both normal and high-fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and that the LH pulse amplitude was reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and the associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat. © 2014 British Society for Neuroendocrinology.

  12. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

    Science.gov (United States)

    Li, Song; Wang, Baolu; Xu, Yan; Zhang, Junjie

    2011-02-12

    Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

  13. Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction

    Science.gov (United States)

    Raasch, Walter; Schäfer, Ulrich; Qadri, Fatimunnisa; Dominiak, Peter

    2002-01-01

    Since agmatine has been identified as a clonidine displacing substance (CDS), the aim of this study was to investigate whether agmatine can mimic CDS-induced cardiovascular reactions in organ bath experiments, pithed spontaneously hypertensive rats (SHR) and anaesthetized SHR.Intravenously-administered agmatine significantly reduced the blood pressure and heart rate of anaesthetized SHR at doses higher than 1 and 3 mg kg−1, respectively. These effects are probably mediated via central mechanisms, since there was an approximate 8 fold rightward shift of the dose-response curve in the pithed SHR (indicating a weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine failed to alter the contractility of intact or endothelium-denuded aortal rings. When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was increased without any alteration of heart rate, whereas blood pressure was unchanged and heart rate was increased after injection into the 4th brain ventricle. This suggests that haemodynamic reaction patterns after central application are related to distinct influences on central cardiovascular mechanisms.Agmatine reduces noradrenaline release in pithed SHR while α2-adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I1-binding sites are selectively blocked with AGN192403. This suggests that agmatine may modulate noradrenaline release in the same way that clonidine does, i.e. via imidazoline binding sites; this involves a reduction in sympathetic tone which in turn reduces blood pressure and heart rate.Finally, CDS-like cardiovascular activity appears not to be due to agmatine, since (i) blood pressure in anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did not antagonize the blood pressure reaction to clonidine in pithed or anaesthetized SHR. PMID:11834614

  14. A preliminary report on the contact-independent antagonism of Pseudogymnoascus destructans by Rhodococcus rhodochrous strain DAP96253.

    Science.gov (United States)

    Cornelison, Christopher T; Keel, M Kevin; Gabriel, Kyle T; Barlament, Courtney K; Tucker, Trudy A; Pierce, George E; Crow, Sidney A

    2014-09-26

    The recently-identified causative agent of White-Nose Syndrome (WNS), Pseudogymnoascus destructans, has been responsible for the mortality of an estimated 5.5 million North American bats since its emergence in 2006. A primary focus of the National Response Plan, established by multiple state, federal and tribal agencies in 2011, was the identification of biological control options for WNS. In an effort to identify potential biological control options for WNS, multiply induced cells of Rhodococcus rhodochrous strain DAP96253 was screened for anti-P. destructans activity. Conidia and mycelial plugs of P. destructans were exposed to induced R. rhodochrous in a closed air-space at 15°C, 7°C and 4°C and were evaluated for contact-independent inhibition of conidia germination and mycelial extension with positive results. Additionally, in situ application methods for induced R. rhodochrous, such as fixed-cell catalyst and fermentation cell-paste in non-growth conditions, were screened with positive results. R. rhodochrous was assayed for ex vivo activity via exposure to bat tissue explants inoculated with P. destructans conidia. Induced R. rhodochrous completely inhibited growth from conidia at 15°C and had a strong fungistatic effect at 4°C. Induced R. rhodochrous inhibited P. destructans growth from conidia when cultured in a shared air-space with bat tissue explants inoculated with P. destructans conidia. The identification of inducible biological agents with contact-independent anti- P. destructans activity is a major milestone in the development of viable biological control options for in situ application and provides the first example of contact-independent antagonism of this devastating wildlife pathogen.

  15. Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat.

    Science.gov (United States)

    Pereira, Mariana; Farrar, Andrew M; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D; Morrell, Joan I

    2011-01-01

    Mesolimbic dopamine (DA), particularly in the nucleus accumbens, importantly regulates activational aspects of maternal responsiveness. DA antagonism and accumbens DA depletions interfere with early postpartum maternal motivation by selectively affecting most forms of active maternal behaviors, while leaving nursing behavior relatively intact. Considerable evidence indicates that there is a functional interaction between DA D2 and adenosine A(2A) receptors in striatal areas, including the nucleus accumbens. This study was conducted to determine if adenosine A(2A) receptor antagonism could reverse the effects of DA receptor antagonism on early postpartum maternal behavior. The adenosine A(2A) receptor antagonist MSX-3 (0.25-2.0 mg/kg, IP) was investigated for its ability to reverse the effects of the DA D2 receptor antagonist haloperidol (0.1 mg/kg, IP) on the maternal behavior of early postpartum female rats. Haloperidol severely impaired the expression of active maternal components, including retrieval and grouping the pups at the nest site, pup licking, and nest building. Co-administration of MSX-3 (0.25-2.0 mg/kg, IP) with haloperidol produced a dose-related attenuation of the haloperidol-induced behavioral deficits in early postpartum females. Doses of MSX-3 that effectively reversed the effects of haloperidol (0.5, 1.0 mg/kg), when administered in the absence of haloperidol, did not affect maternal responding or locomotor activity. Adenosine and DA systems interact to regulate early postpartum maternal responsiveness. This research may potentially contribute to the development of strategies for treatments of psychiatric disorders during the postpartum period, with particular emphasis in maintaining or restoring the mother-infant relationship.

  16. Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2011-01-01

    Full Text Available Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata, in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues. Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

  17. [Agonism and antagonism].

    Science.gov (United States)

    Rey, Anne-Lise

    2016-12-01

    This essay considers dissensus as the starting point for the construction of a common epistemic space rather than as the acknowledgement of an irreducible disagreement. In the argumentative confrontation and disagreements, we do not want to identify a process which might lead to agreement through rational debate. The aim of this essay is rather to understand how dissensus leads to the constitution of plural communities. It discusses a certain number of texts of political philosophy (Habermas, Mouffe, etc.), where the notion of agreement is crucial to an analysis of argumentative confrontations. This essay uses the hypothesis to analyse the circulation of Leibniz's dynamics in his correspondence with De Volder. This perspective shows eventually that dissensus is not an obstacle but the basis on which multiple circulations of theories are possible.

  18. Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects: Role of liposolubility and autophagic flux and antagonism by cholesterol ablation

    Energy Technology Data Exchange (ETDEWEB)

    Parks, Alexandre; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2016-08-15

    Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et{sub 3}N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et{sub 3}Ns with essentially no cell type specificity. Predictors of s-Et{sub 3}N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et{sub 3}N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et{sub 3}N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. - Highlights: • Cation trapping in acidic cell compartments induces a cytostatic effect. • A series of substituted triethylamines has been

  19. Dual interaction of agmatine with the rat α2D-adrenoceptor: competitive antagonism and allosteric activation

    Science.gov (United States)

    Molderings, G J; Menzel, S; Kathmann, M; Schlicker, E; Göthert, M

    2000-01-01

    In segments of rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution, the influence of agmatine on the electrically evoked [3H]-noradrenaline release, the EP3 prostaglandin receptor-mediated and the α2D-adrenoceptor-mediated inhibition of evoked [3H]-noradrenaline release was investigated. Agmatine (0.1–10 μM) by itself was without effect on evoked [3H]-noradrenaline release. In the presence of 10 μM agmatine, the prostaglandin E2(PGE2)-induced EP3-receptor-mediated inhibition of [3H]-noradrenaline release was not modified, whereas the α2D-adrenoceptor-mediated inhibition of [3H]-noradrenaline release induced by noradrenaline, moxonidine or clonidine was more pronounced than in the absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced inhibition of [3H]-noradrenaline release. Agmatine concentration-dependently inhibited the binding of [3H]-clonidine and [3H]-rauwolscine to rat brain cortex membranes (Ki values 6 μM and 12 μM, respectively). In addition, 30 and 100 μM agmatine increased the rate of association and decreased the rate of dissociation of [3H]-clonidine resulting in an increased affinity of the radioligand for the α2D-adrenoceptors. [14C]-agmatine labelled specific binding sites on rat brain cortex membranes. In competition experiments. [14C]-agmatine was inhibited from binding to its specific recognition sites by unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the present data indicate that agmatine both acts as an antagonist at the ligand recognition site of the α2D-adrenoceptor and enhances the effects of α2-adrenoceptor agonists probably by binding to an allosteric binding site of the α2D-adrenoceptor which seems to be labelled by [14C]-agmatine. PMID:10928978

  20. Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects: Role of liposolubility and autophagic flux and antagonism by cholesterol ablation

    International Nuclear Information System (INIS)

    Parks, Alexandre; Marceau, François

    2016-01-01

    Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et 3 N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et 3 Ns with essentially no cell type specificity. Predictors of s-Et 3 N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et 3 N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et 3 N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant. - Highlights: • Cation trapping in acidic cell compartments induces a cytostatic effect. • A series of substituted triethylamines has been studied in 4 cell

  1. Ant-caterpillar antagonism at the community level: interhabitat variation of tritrophic interactions in a neotropical savanna.

    Science.gov (United States)

    Sendoya, Sebastián F; Oliveira, Paulo S

    2015-03-01

    Ant foraging on foliage can substantially affect how phytophagous insects use host plants and represents a high predation risk for caterpillars, which are important folivores. Ant-plant-herbivore interactions are especially pervasive in cerrado savanna due to continuous ant visitation to liquid food sources on foliage (extrafloral nectaries, insect honeydew). While searching for liquid rewards on plants, aggressive ants frequently attack or kill insect herbivores, decreasing their numbers. Because ants vary in diet and aggressiveness, their effect on herbivores also varies. Additionally, the differential occurrence of ant attractants (plant and insect exudates) on foliage produces variable levels of ant foraging within local floras and among localities. Here, we investigate how variation of ant communities and of traits among host plant species (presence or absence of ant attractants) can change the effect of carnivores (predatory ants) on herbivore communities (caterpillars) in a cerrado savanna landscape. We sampled caterpillars and foliage-foraging ants in four cerrado localities (70-460 km apart). We found that: (i) caterpillar infestation was negatively related with ant visitation to plants; (ii) this relationship depended on local ant abundance and species composition, and on local preference by ants for plants with liquid attractants; (iii) this was not related to local plant richness or plant size; (iv) the relationship between the presence of ant attractants and caterpillar abundance varied among sites from negative to neutral; and (v) caterpillars feeding on plants with ant attractants are more resistant to ant predation than those feeding on plants lacking attractants. Liquid food on foliage mediates host plant quality for lepidopterans by promoting generalized ant-caterpillar antagonism. Our study in cerrado shows that the negative effects of generalist predatory ants on herbivores are detectable at a community level, affecting patterns of abundance and

  2. BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Cione, Erika [Department of Pharmacy, Health and Nutritional Sciences, Ed. Polifunzionale, University of Calabria, 87036 Rende, CS (Italy); Fletcher, Steven [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Kane, Maureen A., E-mail: mkane@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States)

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.

  3. Utility of the ceftazidime-imipenem antagonism test (CIAT to detect and confirm the presence of inducible AmpC beta-lactamases among enterobacteriaceae

    Directory of Open Access Journals (Sweden)

    Vlademir Vicente Cantarelli

    Full Text Available Detection of AmpC beta-lactamase production by enterobacteria has been problematic. Contrary to ESBLs, no specific guidelines are available for detection and confirmation of AmpC production by clinical relevant microorganisms. Moreover, some bacterial species may produce inducible AmpC beta-lactamases that can be easily overlooked by routine susceptibility tests. We reported here a new test based on the strong inducible effect of imipenem on AmpC genes and the consequent antagonism with ceftazidime. This test is very simple and proved to be helpful in detecting AmpC-inducible enzymes among several species of clinical isolates.

  4. Metabotropic Glutamate Receptor I (mGluR1) Antagonism Impairs Cocaine-Induced Conditioned Place Preference via Inhibition of Protein Synthesis

    OpenAIRE

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-qing; Liu, Qing-song

    2013-01-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abus...

  5. Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism.

    Science.gov (United States)

    Kashif, Muhammad; Andersson, Claes; Mansoori, Sharmineh; Larsson, Rolf; Nygren, Peter; Gustafsson, Mats G

    2017-11-28

    We analyzed survival effects for 15 different pairs of clinically relevant anti-cancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair. COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy™ II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of significant effect per cell line. In conclusion, the integrated Bliss and Loewe interaction analysis based on non-parametric statistics may provide more robust interaction analyses and reveal complex patterns of synergy and antagonism.

  6. The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate

    Directory of Open Access Journals (Sweden)

    Esteve Pilar

    2008-08-01

    Full Text Available Abstract Background Secreted frizzled related proteins (SFRPs are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (SfrpCRD related to the extracellular portion of Frizzled (Fz, Wnt receptors and the Netrin module (SfrpNTR defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that SfrpCRD interferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the SfrpNTR has been barely addressed. Results Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1NTR mimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1NTR. In contrast, the Sfrp1CRD cannot mirror the function of the entire molecule in vivo but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity. Conclusion On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.

  7. Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.

    Science.gov (United States)

    Ring, Rebecca M; Regan, Ciaran M

    2013-10-01

    The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in the forced swim paradigm, and enhances dopamine turnover in the frontal cortex. Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce the associated elevations of hypothalamic corticotrophin-releasing factor (CRF) and restore the reductions in hypothalamic BDNF expression. Here we demonstrate chronic administration of captodiamine to have no significant effect on hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma-1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF expression. Regulation of BDNF expression by captodiamine was associated with increased phosphorylation of transcription factor CREB and mediated through sigma-1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of two separate signalling pathways was confirmed by immunolocalisation of each receptor to distinct cell populations in the paraventricular nucleus of the hypothalamus. Increased BDNF induced by captodiamine was also associated with enhanced expression of synapsin, but not PSD-95, suggesting induction of long-term structural plasticity between hypothalamic synapses. These unique features of captodiamine may contribute to its ability to ameliorate stress-induced anhedonia as the hypothalamus plays a prominent role in regulating HPA axis activity.

  8. A novel ion-beam-mutation effect application in identification of gene involved in bacterial antagonism to fungal infection of ornamental crops

    Science.gov (United States)

    Mahadtanapuk, S.; Teraarusiri, W.; Nanakorn, W.; Yu, L. D.; Thongkumkoon, P.; Anuntalabhochai, S.

    2014-05-01

    This work is on a novel application of ion beam effect on biological mutation. Bacillus licheniformis (B. licheniformis) is a common soil bacterium with an antagonistic effect on Curcuma alismatifolia Gagnep. and Chrysanthemum indicum Linn. In an attempt to control fungal diseases of local crops by utilizing B. licheniformis, we carried out gene analysis of the bacterium to understand the bacterial antagonistic mechanism. The bacterial cells were bombarded to induce mutations using nitrogen ion beam. After ion bombardment, DNA analysis revealed that the modified polymorphism fragment present in the wild type was missing in a bacterial mutant which lost the antifungal activity. The fragments conserved in the wild type but lost in the mutant bacteria was identified to code for the thioredoxin reductase (TrxR) gene. The gene analysis showed that the TrxR gene from B. licheniformis had the expression of the antagonism to fungi in a synchronous time evolution with the fungus inhibition when the bacteria were co-cultivated with the fungi. The collective results indicate the TrxR gene responsible for the antagonism of bacteria B. licheniformis to fungal infection.

  9. Antagonism of the morphine-induced locomotor activation of mice by fructose: comparison with other opiates and sugars, and sugar effects on brain morphine.

    Science.gov (United States)

    Brase, D A; Ward, C R; Bey, P S; Dewey, W L

    1991-01-01

    The mouse locomotor activation test of opiate action in a 2+2 dose parallel line assay was used in a repeated testing paradigm to determine the test, opiate and hexose specificities of a previously reported antagonism of morphine-induced antinocociception by hyperglycemia. In opiate specificity studies, fructose (5 g/kg, i.p.) significantly reduced the potency ratio for morphine and methadone, but not for levorphanol, meperidine or phenazocine when intragroup comparisons were made. In intergroup comparisons, fructose significantly reduced the potencies of levorphanol and phenazocine, but not methadone or meperidine. In hexose/polyol specificity studies, tagatose and fructose significantly reduced the potency ratio for morphine, whereas glucose, galactose, mannose and the polyols, sorbitol and xylitol, caused no significant decrease in potency. Fructose, tagatose, glucose and mannose (5 g/kg, i.p.) were tested for effects on brain morphine levels 30 min after morphine (60 min after sugar), and all four sugars significantly increased brain morphine relative to saline-pretreated controls. It is concluded that the antagonism of morphine by acute sugar administration shows specificity for certain sugars and occurs despite sugar-induced increases in the distribution of morphine to the brain. Furthermore, the effects of fructose show an opiate specificity similar to that of glucose on antinociception observed previously in our laboratory, except that methadone was also significantly inhibited in the present study, when a repeated-testing experimental design was used.

  10. Estudio del antagonismo de algunas especies de Trichoderma sobre Fusarium Oxysporum y Rhizoctonia Solani Antagonism studies of Trichoderma sp.p.. with Fusarium oxysporum and Rhizoctonia solani

    Directory of Open Access Journals (Sweden)

    Elias Ricardo

    1989-12-01

    Full Text Available En este trabajo se estudió el antagonismo de algunos aislamientos del hongo Trichoderma obtenidos de suelos colornbianos en el control de Fusarium oxysporum y Rhizoctonia solani. En los ensayos "in vitre" se observó un marcado antagonismo entre las colonias de los aislamientos de Trichoderma sobre R. sotsni, con una reducción apreciable
    del tamaño de la colonia y un antaqonismo menor sobre F. oxysporum. En los ensayos de parasitismo a nivel microscópico, se observó una gran interacción entre alqunos
    de los aislamientos de T. harzianum y T. hamatum y el patógéno R. solani rnanifestado por el enrollamiento, penetración, fragmentación y lisis de las hifas del patoqeno.
    Los aislamientos de Trichoderma causaron un retraso en la aparición de los síntomas, una reducción en la severidad de la
    enfermedad. y un menor número de plantas enfermas ocasionadas por F. oxysporum f. sp, cucumerinum en pepino cohombro, y su efecto fue superior en todos los casos a la
    aplicación del fungicida benomil. Los aislamientos del antagonista aumentaron la qerminación de las semillas, la emergencia y el tamaño de las plántulas y redujeron la severidad de la enfermedad ocasionada por R. solani en fríjol.Several experiments were conducted to study the antagonism of 17 isolates of Trichoderma from Colombian soils with Fusarium oxysporum and Rhizoctonia solani. In "in vitro" tests, a high antagonism between colonies was found being greater the antagonism of Trichoderma with R. solani. At the microscopic level it was observed a great interaction between T. harzianum and T. hamatum with R. solani in such a way that the hyphae of the pathogen showed coiling, penetration, fragmentation and lysis. The Trichoderma isolates caused reduction in the disease severity, in the incubation period and a lower number of diseased cucumber plants when they were inoeulated with F. oxysporum f. sp, cucumerinum and these effects were better than Benomyl

  11. GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet

    DEFF Research Database (Denmark)

    McClean, Paula L; Irwin, Nigel; Cassidy, Roslyn S

    2007-01-01

    The gut hormone gastric inhibitory polypeptide (GIP) plays a key role in glucose homeostasis and lipid metabolism. This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro(3))GIP, in mice previously fed a high-fat diet for 160 days to induce...... obesity and related diabetes. Daily intraperitoneal injection of (Pro(3))GIP over 50 days significantly decreased body weight compared with saline-treated controls, with a modest increase in locomotor activity but no change of high-fat diet intake. Plasma glucose, glycated hemoglobin, and pancreatic......))GIP concentrations peaked rapidly and remained elevated 24 h after injection. These data indicate that GIP receptor antagonism using (Pro(3))GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet....

  12. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects

    DEFF Research Database (Denmark)

    Meier, Juris J; Kemmeries, Guido; Holst, Jens Juul

    2005-01-01

    . On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at -30 min per oral), or erythromycin (200 mg intravenously from -30 to -15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml......, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 +/- 4 years, BMI 25.0 +/- 4.9 kg/m2) were studied with an infusion of GLP-1 (0.8 pmol.kg(-1).min(-1) from -30 to 240 min) or placebo...... technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P drugs used had no effect. Postprandial...

  13. Bacillus species (BT42) isolated from Coffea arabica L. rhizosphere antagonizes Colletotrichum gloeosporioides and Fusarium oxysporum and also exhibits multiple plant growth promoting activity.

    Science.gov (United States)

    Kejela, Tekalign; Thakkar, Vasudev R; Thakor, Parth

    2016-11-18

    Colletotrichum and Fusarium species are among pathogenic fungi widely affecting Coffea arabica L., resulting in major yield loss. In the present study, we aimed to isolate bacteria from root rhizosphere of the same plant that is capable of antagonizing Colletotrichum gloeosporioides and Fusarium oxysporum as well as promotes plant growth. A total of 42 Bacillus species were isolated, one of the isolates named BT42 showed maximum radial mycelial growth inhibition against Colletotrichum gloeosporioides (78%) and Fusarium oxysporum (86%). BT42 increased germination of Coffee arabica L. seeds by 38.89%, decreased disease incidence due to infection of Colletotrichum gloeosporioides to 2.77% and due to infection of Fusarium oxysporum to 0 (p Fusarium oxysporum. The mechanism of action of inhibition of the pathogenic fungi found to be synergistic effects of secondary metabolites, lytic enzymes, and siderophores. The major inhibitory secondary metabolite identified as harmine (β-carboline alkaloids).

  14. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism.

    Science.gov (United States)

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3-4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates.

  15. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  16. Metabotropic glutamate receptor I (mGluR1) antagonism impairs cocaine-induced conditioned place preference via inhibition of protein synthesis.

    Science.gov (United States)

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-Qing; Liu, Qing-Song

    2013-06-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abuse. We report that group I mGluR agonist DHPG induced more pronounced initial depression of inhibitory postsynaptic currents (IPSCs) followed by modest long-term depression (I-LTD) in dopamine neurons of rat ventral tegmental area (VTA) through the activation of mGluR1. The early component of DHPG-induced depression of IPSCs was mediated by the cannabinoid CB1 receptors, while DHPG-induced I-LTD was dependent on protein synthesis. Western blotting analysis indicates that mGluR1 was coupled to extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways to increase translation. We also show that cocaine conditioning activated translation machinery in the VTA via an mGluR1-dependent mechanism. Furthermore, intra-VTA microinjections of mGluR1 antagonist JNJ16259685 and protein synthesis inhibitor cycloheximide significantly attenuated or blocked the acquisition of cocaine-induced conditioned place preference (CPP) and activation of translation elongation factors. Taken together, these results suggest that mGluR1 antagonism inhibits de novo protein synthesis; this effect may block the formation of cocaine-cue associations and thus provide a mechanism for the reduction in CPP to cocaine.

  17. Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study

    Science.gov (United States)

    Fervaha, Gagan; Caravaggio, Fernando; Mamo, David C.; Mulsant, Benoit H.; Pollock, Bruce G.; Nakajima, Shinichiro; Gerretsen, Philip; Rajji, Tarek K.; Mar, Wanna; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Remington, Gary; Graff-Guerrero, Ariel

    2016-01-01

    Rationale Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial. Objective The objective of this study was to examine the relationship between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptoms in patients with schizophrenia. Methods Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [11C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40% from the baseline dose. Results No significant relationship was found between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship. Conclusions Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioural effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined. PMID:27557949

  18. The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.

    Science.gov (United States)

    Sirohi, Sunil; Dighe, Shveta V; Madia, Priyanka A; Yoburn, Byron C

    2009-08-01

    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.

  19. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Wu, Wen-Jeng [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Huang, Huei-Sheng, E-mail: huanghs@mail.ncku.edu.tw [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

    2015-05-15

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF

  20. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    International Nuclear Information System (INIS)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling; Yeh, Bi-Wen; Wu, Wen-Jeng; Huang, Huei-Sheng

    2015-01-01

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21 WAF1/CIP1 ) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF mediates

  1. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver

    DEFF Research Database (Denmark)

    Elmen, Joachim; Lindow, Morten; Silahtaroglu, Asli

    2008-01-01

    ’end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake...... of the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122 in treated mice. Functional antagonism of miR-122 was inferred from a low cholesterol phenotype and derepression within 24 h of 199 liver mRNAs showing significant enrichment for mi...

  2. Crystal structure of Lymnaea stagnalis AChBP complexed with the potent nAChR antagonist DHβE suggests a unique mode of antagonism.

    Directory of Open Access Journals (Sweden)

    Azadeh Shahsavar

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed, activated (open, and desensitized (closed states. The acetylcholine binding protein (AChBP is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls in complex with dihydro-β-erythroidine (DHβE, which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

  3. NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Jinmin Gao

    2015-03-01

    Full Text Available The formation of DNA double-strand breaks (DSBs must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.

  4. An in vitro study of peptide-loaded alginate nanospheres for antagonizing the inhibitory effect of Nogo-A protein on axonal growth

    International Nuclear Information System (INIS)

    Zhai, Peng; Chen, X B; Schreyer, David J

    2015-01-01

    The adult mammalian central nervous system has limited ability to regenerate after injury. This is due, in part, to the presence of myelin-associated axon growth inhibitory proteins such as Nogo-A that bind and activate the Nogo receptor, leading to profound inhibition of actin-based motility within the growing axon tip. This paper presents an in vitro study of the use of a Nogo receptor-blocking peptide to antagonize the inhibitory effect of Nogo-A on axon growth. Alginate nanospheres were fabricated using an emulsion technique and loaded with Nogo receptor-blocking peptide, or with other model proteins. Protein release profiles were studied, and retention of the bioactivity of released proteins was verified. Primary dorsal root ganglion neurons were cultured and their ability to grow neurites was challenged with Nogo-A chimeric protein in the absence or presence of Nogo receptor antagonist peptide-loaded alginate nanospheres. Our results demonstrate that peptide released from alginate nanospheres could overcome the growth inhibitory effect of Nogo-A, suggesting that a similar peptide delivery strategy using alginate nanospheres might be used to improve axon regeneration within the injured central nervous system. (paper)

  5. Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors.

    Science.gov (United States)

    Mega, Tiziana; Lupia, Michela; Amodio, Nicola; Horton, Sarah J; Mesuraca, Maria; Pelaggi, Daniela; Agosti, Valter; Grieco, Michele; Chiarella, Emanuela; Spina, Raffaella; Moore, Malcolm A S; Schuringa, Jan Jacob; Bond, Heather M; Morrone, Giovanni

    2011-07-01

    Zinc finger protein 521 (EHZF/ZNF521) is a multi-functional transcription co-factor containing 30 zinc fingers and an amino-terminal motif that binds to the nucleosome remodelling and histone deacetylase (NuRD) complex. ZNF521 is believed to be a relevant player in the regulation of the homeostasis of the hematopoietic stem/progenitor cell compartment, however the underlying molecular mechanisms are still largely unknown. Here, we show that this protein plays an important role in the control of B-cell development by inhibiting the activity of early B-cell factor-1 (EBF1), a master factor in B-lineage specification. In particular, our data demonstrate that: (1) ZNF521 binds to EBF1 via its carboxyl-terminal portion and this interaction is required for EBF1 inhibition; (2) NuRD complex recruitment by ZNF521 is not essential for the inhibition of transactivation of EBF1-dependent promoters; (3) ZNF521 represses EBF1 target genes in a human B-lymphoid molecular context; and (4) RNAi-mediated silencing of ZNF521/Zfp521 in primary human and murine hematopoietic progenitors strongly enhances the generation of B-lymphocytes in vitro. Taken together, our data indicate that ZNF521 can antagonize B-cell development and lend support to the notion that it may contribute to conserve the multipotency of primitive lympho-myeloid progenitors by preventing or delaying their EBF1-driven commitment toward the B-cell lineage.

  6. Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

    Science.gov (United States)

    Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

    2011-03-01

    The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

  7. Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, and In Vivo Efficacy Studies on Mice to Antagonize Cyanide Intoxication

    Directory of Open Access Journals (Sweden)

    Ilona Petrikovics

    2011-01-01

    Full Text Available Present studies have focused on a novel cyanide antidotal system, on the coencapsulation of a new sulfur donor DTO with rhodanese within sterically stabilized liposomes. The optimal lipid composition for coencapsulation of DTO with rhodanese is the combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, cationic lipid (DOTAP, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol-2000] ammonium salt (with molar ratios of 82.7 : 9.2 : 3.0 : 5.1. With the optimized compositions, prophylactic and therapeutic in vivo efficacy studies were carried out in a mice model. When DTO was coencapsulated with rhodanese and thiosulfate the prophylactic antidotal protection was 4.9×LD50. Maximum antidotal protection against cyanide intoxication (15×LD50 was achieved with coencapsulated rhodanese and DTO/thiosulfate in combination with sodium nitrite. When applied therapeutically, 100% survival rate (6/6 was achieved at 20 mg/kg cyanide doses with the encapsulated DTO-rhodanese-thiosulfate antidotal systems with and without sodium nitrite. These data are indicating that the appropriately formulated DTO is a promising sulfur donor for cyanide antagonism.

  8. Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

    Directory of Open Access Journals (Sweden)

    Padhy Rabindra N.

    2014-03-01

    Full Text Available Effects of chemical fertilizers (urea, super phosphate and potash on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical fertilizers, individually. Urea at the 10 ppm level was growth stimulatory and at the 50 ppm level it was growth inhibitory in control cultures, while at 100 ppm it was antagonistic, i.e. toxicity-enhancing along with carbaryl, individually to the cyanobacterium, antagonism was recorded. Urea at 50 ppm had toxicity reducing effect with carbaryl or carbofuran. At 100 and 250 ppm carbofuran levels, 50 ppm urea only had a progressive growth enhancing effect, which was marked well at 250 ppm carbofuran level, a situation of synergism. Super phosphate at the 10 ppm level only was growth promoting in control cultures, but it was antagonistic at its higher levels (50 and 100 ppm along with both insecticides, individually. Potash (100, 200, 300 and 400 ppm reduced toxicity due to carbaryl 20 and carbofuran 250 ppm levels, but potash was antagonistic at the other insecticide levels. The data clearly showed that the chemical fertilizers used were antagonistic with both the insecticides during toxicity to Cylindrospermum sp.

  9. Antagonism at combined effects of chemical fertilizers and carbamate insecticides on the rice-field N2-fixing cyanobacterium Cylindrospermum sp. in vitro

    Science.gov (United States)

    Nayak, Nabakishore; Rath, Shakti

    2014-01-01

    Effects of chemical fertilizers (urea, super phosphate and potash) on toxicities of two carbamate insecticides, carbaryl and carbofuran, individually to the N2-fixing cyanobacterium, Cylindrospermum sp. were studied in vitro at partially lethal levels (below highest permissive concentrations) of each insecticide. The average number of vegetative cells between two polar heterocysts was 16.3 in control cultures, while the mean value of filament length increased in the presence of chemical fertilizers, individually. Urea at the 10 ppm level was growth stimulatory and at the 50 ppm level it was growth inhibitory in control cultures, while at 100 ppm it was antagonistic, i.e. toxicity-enhancing along with carbaryl, individually to the cyanobacterium, antagonism was recorded. Urea at 50 ppm had toxicity reducing effect with carbaryl or carbofuran. At 100 and 250 ppm carbofuran levels, 50 ppm urea only had a progressive growth enhancing effect, which was marked well at 250 ppm carbofuran level, a situation of synergism. Super phosphate at the 10 ppm level only was growth promoting in control cultures, but it was antagonistic at its higher levels (50 and 100 ppm) along with both insecticides, individually. Potash (100, 200, 300 and 400 ppm) reduced toxicity due to carbaryl 20 and carbofuran 250 ppm levels, but potash was antagonistic at the other insecticide levels. The data clearly showed that the chemical fertilizers used were antagonistic with both the insecticides during toxicity to Cylindrospermum sp. PMID:26038669

  10. NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis.

    Science.gov (United States)

    Gao, Jinmin; Kim, Hyun-Min; Elia, Andrew E; Elledge, Stephen J; Colaiácovo, Monica P

    2015-03-01

    The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.

  11. Paenibacillus polymyxa A26 sfp-type phosphopantetheinyl transferase inactivation limits bacterial antagonism against Fusarium graminearum but not of F. culmorum

    Directory of Open Access Journals (Sweden)

    Islam A eAbd El Daim

    2015-05-01

    Full Text Available Fusarium graminearum and F. culmorum are the causing agents of a destructive disease known as Fusarium head blight (FHB. FHB is a re-emerging disease in small grain cereals which impairs both the grain yield and the quality. Most serious consequence is the contamination of grain with Fusarium mycotoxins that are severe threat to humans and animals. Biological control has been suggested as one of the integrated management strategies to control FHB. Paenibacillus polymyxa is considered as a promising biocontrol agent due to its unique antibiotic spectrum. In order to optimize strain A26 production, formulation and application strategies traits important for its compatibility need to be revealed. Here we developed a toolbox comprising of dual culture plate assays and wheat kernel assays including simultaneous monitoring of FHB causing pathogens A26 and mycotoxins produced. Using this system we show that, besides generally known lipopeptide antibiotic production by P. polymyxa, biofilm formation ability may play a crucial role in the case of stain A26 F. culmorum antagonism.

  12. In Vivo Neurometabolic Profiling to Characterize the Effects of Social Isolation and Ketamine-Induced NMDA Antagonism: A Rodent Study at 7.0 T

    Science.gov (United States)

    Napolitano, Antonio

    2014-01-01

    Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy (1H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-d-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent ​1H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthe sia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development. PMID:23671195

  13. A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites

    Science.gov (United States)

    Haque, Jamil A.; McDonald, Matthew G.; Kulman, John D.

    2014-01-01

    Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR) by depleting reduced vitamin K that is required for posttranslational modification of vitamin K–dependent clotting factors. In vitro prediction of the in vivo potency of vitamin K antagonists is complicated by the complex multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay that enables quantitative analysis of γ-glutamyl carboxylation and its antagonism in live cells. We engineered a human embryonic kidney (HEK) 293–derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of proline-rich Gla protein 2. Maximal γ-glutamyl carboxylation of F9CH required vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin at a physiologically relevant concentration. Cellular γ-glutamyl carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers (S > R) consistent with their in vivo potencies. We further analyzed the structure-activity relationship for inhibition of γ-glutamyl carboxylation by warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus. After correction for in vivo concentration and protein binding, 10-hydroxywarfarin and warfarin alcohols were predicted to be the most potent inhibitory metabolites in vivo. PMID:24297869

  14. In vivo neurometabolic profiling to characterize the effects of social isolation and ketamine-induced NMDA antagonism: a rodent study at 7.0 T.

    Science.gov (United States)

    Napolitano, Antonio; Shah, Khalid; Schubert, Mirjam I; Porkess, Veronica; Fone, Kevin C F; Auer, Dorothee P

    2014-05-01

    Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy ((1)H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-D-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent (1)H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthesia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development.

  15. Biochanin-A antagonizes the interleukin-1β-induced catabolic inflammation through the modulation of NFκB cellular signaling in primary rat chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Su [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Cho, In-A; Kang, Kyeong-Rok [Department of Dental Bioengineering, Chosun University, Gwangju, 61452 (Korea, Republic of); You, Jae-Seek [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Yu, Sang-Joun [Department of Periodontology, Chosun University, Gwangju, 61452 (Korea, Republic of); Lee, Gyeong-Je [Department of Prosthodontics, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Yo-Seob [Department of Oral and Maxillofacial Radiology, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Chun Sung; Kim, Do Kyung [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of); Kim, Su-Gwan [Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju, 61452 (Korea, Republic of); Seo, Young-Woo [Korea Basic Science Institute, Gwangju Center, Chonnam National University, Gwangju, 61186 (Korea, Republic of); Im, Hee-Jeong [Department of Biochemistry, Rush University Medical Center, Chicago, IL, 60612 (United States); Kim, Jae-Sung, E-mail: js_kim@chosun.ac.kr [Pre-Dentistry, School of Dentistry, Chosun University, Gwangju, 61452 (Korea, Republic of)

    2016-09-02

    Biochanin-A, a phytoestrogen derived from herbal plants, protected from the IL-1β-induced loss of proteoglycans through the suppression of matrix degrading enzymes such as matrix metalloproteinase (MMP)-13, MMP-3, MMP-1, and ADAMTS-5 in primary rat chondrocytes and the knee articular cartilage. It also suppressed the expression of IL-1β-induced catabolic factors such as nitric oxide synthase 2, cyclooxygenase-2, prostaglandin E{sub 2}, and inflammatory cytokines. Furthermore, biochanin-A suppressed the IL-1β-induced phosphorylation of NFκB, and inhibited its nuclear translocation in primary rat chondrocytes. These results indicate that biochanin-A antagonizes the IL-1β-induced catabolic effects through its anti-inflammatory activity that involves the modulation of NFκB signaling. - Highlights: • Biochanin-A is a phytoestrogen derived from medicinal plants. • It suppressed the IL-1β-induced matrix degrading enzymes and catabolic factors. • It inhibited IL-1β-induced proteoglycan loss in chondrocytes and cartilage tissues. • Its anti-catabolic effects were mediated by modulation of NFκB signaling. • It may be used as a potential anti-catabolic biomaterial for osteoarthritis.

  16. Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124.

    Science.gov (United States)

    Chang, Zhangmei; Wang, Yan; Bian, Liang; Liu, Qingqing; Long, Jian-Er

    2017-12-01

    Enterovirus 71 (EV71) has caused major outbreaks of hand, foot and mouth disease. EV71 infections increase the production of many host cytokines and pro-inflammatory factors, including interleukin (IL)-6, IL-10 and COX-2. Some of these molecules could stimulate the signal transducer and activator of transcription 3 (STAT3), which plays a key role in regulating host immune responses and several viral diseases. However, the role of STAT3 in EV71 infection remains unknown. This study found that the phosphorylation levels of STAT3 (p Y705 -STAT3) are closely related to EV71 infection. Further experiments revealed that STAT3 exerts an anti-EV71 activity. However, the antiviral activity of STAT3 is partially antagonized by EV71-induced miR-124, which directly targets STAT3 mRNA. Similarly, IL-6R, the α-subunit of the IL-6 receptor complex, exhibits anti-EV71 activity and is directly targeted by the virus-induced miR-124. These results indicate that EV71 can evade host IL-6R- and STAT3-mediated antiviral activities by EV71-induced miR-124. This suggests that controlling miR-124 and the downstream targets, IL-6R and STAT3, might benefit the antiviral treatment of EV71 infection.

  17. Late Pleistocene steppe lion Panthera leo spelaea (Goldfuss, 1810) footprints and bone records from open air sites in northern Germany - Evidence of hyena-lion antagonism and scavenging in Europe

    Science.gov (United States)

    Diedrich, Cajus G.

    2011-07-01

    Bone remains and a trackway of Pantheraichnus bottropensis nov. ichg. ichnsp. of the Late Pleistocene lion Panthera leo spelaea ( Goldfuss, 1810) have been recovered from Bottrop and other open air sites in northern Germany. Some of these bones are from open air hyena den sites. A relative high proportion of lion bones (20%) exhibit bite, chew or nibble marks, or bone crushing and nibbling caused by a large carnivore. Repeated patterns of similar bone damage have been compared to bone remains found at hyena dens in gypsum karst areas and cave sites in northern Germany. Ice Age spotted hyenas have been the main antagonists and the main scavengers on lion carcasses. The remains appear to have been imported often by hyenas into their communal dens, supporting the theory of strong hyena-lion antagonism, similar to the well documented antagonism between modern African lions and spotted hyenas. Most of the lion bones from the open air hyena den at Bottrop are probably a result of such antagonism, as are the rare remains of these carnivores found within large hyena prey bone accumulations along the Pleistocene rivers. The Emscher River terrace also has the largest quantity of hyena remains from open air river terrace sites in northern Germany. Their cub remains, and incomplete chewed prey bones from mammoths and woolly rhinoceroses, typical of hyena activity, underline the character of these sites as cub-raising and communal dens, where their prey was accumulated along the riverbanks in a similar manner to modern African hyenas.

  18. The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

    Directory of Open Access Journals (Sweden)

    Baca Chan

    2017-05-01

    Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

  19. Antagonism at the NR2B subunit of NMDA receptors induces increased connectivity of the prefrontal and subcortical regions regulating reward behavior.

    Science.gov (United States)

    Gass, Natalia; Becker, Robert; Sack, Markus; Schwarz, Adam J; Reinwald, Jonathan; Cosa-Linan, Alejandro; Zheng, Lei; von Hohenberg, Christian Clemm; Inta, Dragos; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang; Gass, Peter; Sartorius, Alexander

    2018-04-01

    Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action. The experimental design comprised four parallel groups of rats (N = 37), each receiving (S)-Ketamine, CP-101,606, Ro 25-6981 or saline. After compound injection, we acquired resting-state functional magnetic resonance imaging time series. We used graph theoretical approach to calculate brain network properties. Ketamine and CP-101,606 diminished the global clustering coefficient and small-worldness index. At the nodal level, all compounds induced increased connectivity of the regions mediating reward and cognitive aspects of emotional processing, such as ventromedial prefrontal cortex, septal nuclei, and nucleus accumbens. The dorsal hippocampus and regions involved in sensory processing and aversion, such as superior and inferior colliculi, exhibited an opposite effect. The effects common to ketamine and NR2B-selective compounds were localized to the same brain regions as those reported in depression, but in the opposite direction. The upregulation of the reward circuitry might partially underlie the antidepressant and anti-anhedonic effects of the antagonists and could potentially serve as a translational imaging phenotype for testing putative antidepressants, especially those targeting the NR2B receptor subtype.

  20. Antagonism of bradykinin B2 receptor prevents inflammatory responses in human endothelial cells by quenching the NF-kB pathway activation.

    Directory of Open Access Journals (Sweden)

    Erika Terzuoli

    Full Text Available Bradykinin (BK induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects.We assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC and circulating pro-angiogenic cells (PACs, in producing cell permeability (paracellular flux, migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay and in vivo in mice (matrigel plug and in rat model of experimental osteoarthritis (OA. We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2, prostaglandin E-2 and vascular endothelial growth factor (VEGF.HUVEC, exposed to BK (1-10 µM, showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor.This work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation.

  1. Synergism and Antagonism between Bacillus thuringiensis Vip3A and Cry1 Proteins in Heliothis virescens, Diatraea saccharalis and Spodoptera frugiperda

    Science.gov (United States)

    Lemes, Ana Rita Nunes; Davolos, Camila Chiaradia; Legori, Paula Cristina Brunini Crialesi; Fernandes, Odair Aparecido; Ferré, Juan; Lemos, Manoel Victor Franco; Desiderio, Janete Apparecida

    2014-01-01

    Second generation Bt crops (insect resistant crops carrying Bacillus thuringiensis genes) combine more than one gene that codes for insecticidal proteins in the same plant to provide better control of agricultural pests. Some of the new combinations involve co-expression of cry and vip genes. Because Cry and Vip proteins have different midgut targets and possibly different mechanisms of toxicity, it is important to evaluate possible synergistic or antagonistic interactions between these two classes of toxins. Three members of the Cry1 class of proteins and three from the Vip3A class were tested against Heliothis virescens for possible interactions. At the level of LC50, Cry1Ac was the most active protein, whereas the rest of proteins tested were similarly active. However, at the level of LC90, Cry1Aa and Cry1Ca were the least active proteins, and Cry1Ac and Vip3A proteins were not significantly different. Under the experimental conditions used in this study, we found an antagonistic effect of Cry1Ca with the three Vip3A proteins. The interaction between Cry1Ca and Vip3Aa was also tested on two other species of Lepidoptera. Whereas antagonism was observed in Spodoptera frugiperda, synergism was found in Diatraea saccharalis. In all cases, the interaction between Vip3A and Cry1 proteins was more evident at the LC90 level than at the LC50 level. The fact that the same combination of proteins may result in a synergistic or an antagonistic interaction may be an indication that there are different types of interactions within the host, depending on the insect species tested. PMID:25275646

  2. Diversity of indigenous endophytic bacteria associated with the roots of Chinese cabbage (Brassica campestris L.) cultivars and their antagonism towards pathogens.

    Science.gov (United States)

    Haque, Md Azizul; Yun, Han Dae; Cho, Kye Man

    2016-05-01

    The study aimed to reveal the diversity of endophytic bacteria in the roots of Chinese cabbage (CC) cultivated in two areas in Korea, namely, Seosang-gun (SS) and Haenam-gun (HN), and also in a transgenic plant (TP) from the laboratory. A total of 653 colonies were isolated from the interior of CC roots, comprising 118, 302, and 233 isolates from SS, HN, and TP samples, respectively. Based on 16S rRNA gene sequence analysis, the isolates belonged to four major phylogenetic groups: high-G+C Gram-positive bacteria (HGC-GPB), low-G+C Gram-positive bacteria (LGC-GPB), Proteobacteria, and Bacteriodetes. The most dominant groups in the roots of the SS, HN, and TP cultivars were LGC-GPB (48.3%), Proteobacteria (50.2%), and HGC-GPB (38.2%), respectively. Importantly, most of the isolates that produced cell-walldegrading enzymes belonged to the genus Bacillus. Bacillus sp. (HNR03, TPR06), Bacillus pumilus (SSR07, HNR11, TPR07), and Bacillus subtilis (TPR03) showed high antagonism against the tested food-borne pathogenic bacteria. In addition, Bacillus sp. (HNR03, TPR06), Bacillus pumilus (SSR07, HNR11, HNR17, TPR11), Microbacterium oxidans (SSR09, TPR04), Bacillus cereus HNR10, Pseudomonas sp. HNR13, and Bacillus subtilis (TPR02, TPR03) showed strong antagonistic activity against the fungi Phythium ultimum, Phytophthora capsici, Fusarium oxysporum, and Rhizoctonia solani. The endophytes isolated from the TP cultivar showed the strongest antagonistic reactions against pathogens. This study is the first report on endophytic bacteria from Chinese cabbage roots.

  3. Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

    Science.gov (United States)

    Hancks, Dustin C; Hartley, Melissa K; Hagan, Celia; Clark, Nathan L; Elde, Nels C

    2015-05-01

    A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted

  4. Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

    Directory of Open Access Journals (Sweden)

    Dustin C Hancks

    2015-05-01

    Full Text Available A diverse subset of pattern recognition receptors (PRRs detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1, a PRR that detects double-stranded RNA (dsRNA, despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system

  5. Histone variant H2A.Z antagonizes the positive effect of the transcriptional activator CPC1 to regulate catalase-3 expression under normal and oxidative stress conditions.

    Science.gov (United States)

    Dong, Qing; Wang, Yajun; Qi, Shaohua; Gai, Kexin; He, Qun; Wang, Ying

    2018-05-05

    In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway. Notably, loss of H2A.Z or SWR1 subunits leads to increased binding of a transcription factor, CPC1, at cat-3 locus. Additionally, introduction of plasmids containing gene encoding H2A.Z or SWR1 complex subunits into wild-type strains decreased CAT-3 expression, indicating that H2A.Z counteracts the positive effect of CPC1 to achieve low level cat-3 expression under non-inductive condition. Furthermore, upon oxidative stress, H2A.Z is rapidly evicted from cat-3 locus for the recruitment of CPC1, resulting in robust and full cat-3 gene expression in response to external stimuli. Collectively, this study strongly demonstrates that H2A.Z antagonizes the function of transcription factor to regulate responsive gene transcription under normal conditions and to poise for gene full activation under oxidative stress. Copyright © 2018. Published by Elsevier Inc.

  6. Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation.

    Science.gov (United States)

    Liu, W; Xu, Z; Li, H; Guo, M; Yang, T; Feng, S; Xu, B; Deng, Yu

    2017-09-01

    Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl 2 ) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl 2 treatment (0.6, 1.2, and 2.4 mg kg -1 day -1 ), and curcumin pretreatment (100 mg kg -1 day -1 ) groups. Exposure of HgCl 2 resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg -1 HgCl 2 significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl 2 treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl 2 -induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl 2 hepatotoxicity through antagonizing liver oxidative stress.

  7. Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism.

    Science.gov (United States)

    Han, Xiao; DeBold, Joseph F; Miczek, Klaus A

    2017-09-01

    A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined. The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice. First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration. These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.

  8. Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity.

    Science.gov (United States)

    Palmer, Kirsten R; Kaitu'u-Lino, Tu'uhevaha J; Hastie, Roxanne; Hannan, Natalie J; Ye, Louie; Binder, Natalie; Cannon, Ping; Tuohey, Laura; Johns, Terrance G; Shub, Alexis; Tong, Stephen

    2015-12-01

    In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal circulation, causing endothelial dysfunction and organ injury. A recently described splice variant, sFLT-1 e15a, is primate specific and the most abundant placentally derived sFLT-1. Therefore, it may be the major sFLT-1 isoform contributing to the pathophysiology of preeclampsia. sFLT-1 e15a protein remains poorly characterized: its bioactivity has not been comprehensively examined, and serum levels in normal and preeclamptic pregnancy have not been reported. We generated and validated an sFLT-1 e15a-specific ELISA to further characterize serum levels during pregnancy, and in the presence of preeclampsia. Furthermore, we performed assays to examine the bioactivity and antiangiogenic properties of sFLT-1 e15a protein. sFLT-1 e15a was expressed in the syncytiotrophoblast, and serum levels rose across pregnancy. Strikingly, serum levels were increased 10-fold in preterm preeclampsia compared with normotensive controls. We confirmed sFLT-1 e15a is bioactive and is able to inhibit vascular endothelial growth factor signaling of vascular endothelial growth factor receptor 2 and block downstream Akt phosphorylation. Furthermore, sFLT-1 e15a has antiangiogenic properties. sFLT-1 e15a decreased endothelial cell migration, invasion, and inhibited endothelial cell tube formation. Administering sFLT-1 e15a blocked vascular endothelial growth factor induced sprouts from mouse aortic rings ex vivo. We have demonstrated that sFLT-1 e15a is increased in preeclampsia, antagonizes vascular endothelial growth factor signaling, and has antiangiogenic activity. Future development of diagnostics and therapeutics for preeclampsia should consider targeting placentally derived sFLT-1 e15a. © 2015 American Heart Association, Inc.

  9. Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism.

    Directory of Open Access Journals (Sweden)

    Shridhar Bale

    2012-09-01

    Full Text Available Filoviruses, including Marburg virus (MARV and Ebola virus (EBOV, cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (dsRNA-binding domain (RBD of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules.

  10. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism

    Science.gov (United States)

    Hasbi, Ahmed; Perreault, Melissa L.; Shen, Maurice Y. F.; Zhang, Lucia; To, Ryan; Fan, Theresa; Nguyen, Tuan; Ji, Xiaodong; O'Dowd, Brian F.; George, Susan R.

    2014-01-01

    Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues 404Glu and 405Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.—Hasbi, A., Perreault, M. L., Shen, M. Y. F., Zhang, L., To, R., Fan, T., Nguyen, T., Ji, X., O'Dowd, B. F., George, S. R. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism. PMID:25063849

  11. Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.

    Science.gov (United States)

    Yang, Feiya; Jiang, Xian; Song, Liming; Wang, Huiping; Mei, Zhu; Xu, Zhiqing; Xing, Nianzeng

    2016-03-01

    The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.

  12. Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

    Science.gov (United States)

    Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

    2014-01-01

    Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434

  13. The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity.

    Science.gov (United States)

    Pesavento, Christina; Hengge, Regine

    2012-06-01

    FliZ, a global regulatory protein under the control of the flagellar master regulator FlhDC, was shown to antagonize σ(S)-dependent gene expression in Escherichia coli. Thereby it plays a pivotal role in the decision between alternative life-styles, i.e. FlhDC-controlled flagellum-based motility or σ(S)-dependent curli fimbriae-mediated adhesion and biofilm formation. Here, we show that FliZ is an abundant DNA-binding protein that inhibits gene expression mediated by σ(S) by recognizing operator sequences that resemble the -10 region of σ(S)-dependent promoters. FliZ does so with a structural element that is similar to region 3.0 of σ(S). Within this element, R108 in FliZ corresponds to K173 in σ(S), which contacts a conserved cytosine at the -13 promoter position that is specific for σ(S)-dependent promoters. R108 as well as C(-13) are also crucial for DNA binding by FliZ. However, while a number of FliZ binding sites correspond to known σ(S)-dependent promoters, promoter activity is not a prerequisite for FliZ binding and repressor function. Thus, we demonstrate that FliZ also feedback-controls flagellar gene expression by binding to a site in the flhDC control region that shows similarity only to a -10 element of a σ(S)-dependent promoter, but does not function as a promoter.

  14. Seletividade de herbicidas aplicados em pós-emergência para a cultura da mandioquinha-salsa Peruvian carrot tolerance to post-emergence herbicides

    Directory of Open Access Journals (Sweden)

    R.S. Freitas

    2004-03-01

    and high] with 39 treatments distributed in randomized blocks, with three repetitions. The herbicide doses (g ha-1 were: bentazon (600, 720, and 960, clethodim (84, 96, and 108, fenoxaprop-p-ethyl (68, 90, and 110, flazasulfuron (50, 75, and 100, fluazifop-p-butyl (94, 187, and 250, halosulfuron (75, 112, and 150, imazamox (28, 35, and 42, linuron (900, 1,350, and 1,800, oxadiazon (500, 750, and 1,000, propaquizafop (100, 125, and 150, sethoxydin (184, 230, and 276, and ammonium-glufosinate (200, 300, and 400. The plants were harvested at 49 days after treatment application (DAA. The herbicides halosulfuron, flazasulfuron, imazamox and bentazon caused high toxicity and damage to the crop, being non-selective for Peruvian carrot. Low and medium doses of linuron and oxadiazon, and low dose of ammonium-glufosinate caused toxicity just after spraying, but the crop showed good recovery from 28 DAA. Fluazifop-p-butyl was selective in low doses. Clethodim, fenoxaprop-p-ethyl, propaquizafop, and sethoxydin were the most selective to Peruvian carrot.

  15. Behavioral effects of gamma-hydroxybutyrate, its precursor gamma-butyrolactone, and GABA(B) receptor agonists: time course and differential antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348).

    Science.gov (United States)

    Koek, Wouter; Mercer, Susan L; Coop, Andrew; France, Charles P

    2009-09-01

    Gamma-hydroxybutyrate (GHB) is used therapeutically and recreationally. The mechanism by which GHB produces its therapeutic and recreational effects is not entirely clear, although GABA(B) receptors seem to play an important role. This role could be complex, because there are indications that different GABA(B) receptor mechanisms mediate the effects of GHB and the prototypical GABA(B) receptor agonist baclofen. To further explore possible differences in underlying GABA(B) receptor mechanisms, the present study examined the effects of GHB and baclofen on operant responding and their antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). Pigeons were trained to peck a key for access to food during response periods that started at different times after the beginning of the session. In these pigeons, GHB, its precursor gamma-butyrolactone (GBL), and the GABA(B) receptor agonists baclofen and 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF97541) decreased the rate of responding in a dose- and time-dependent manner. CGP35348 shifted the dose-response curve of each agonist to the right, but the magnitude of the shift differed among the agonists. Schild analysis yielded a pA(2) value of CGP35348 to antagonize GHB and GBL [i.e., 3.9 (3.7-4.2)] that was different (P = 0.0011) from the pA(2) value to antagonize baclofen and SKF97541 [i.e., 4.5 (4.4-4.7)]. This finding is further evidence that the GABA(B) receptor mechanisms mediating the effects of GHB and prototypical GABA(B) receptor agonists are not identical. A better understanding of the similarities and differences between these mechanisms, and their involvement in the therapeutic effects of GHB and baclofen, could lead to more effective medications with fewer adverse effects.

  16. Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

    Science.gov (United States)

    Liou, Kevin; Jepson, Nigel; Buckley, Nicolas; Chen, Vivien; Thomas, Shane; Russell, Elizabeth Anne; Ooi, Sze-Yuan

    2016-04-01

    Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

  17. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik

    2006-01-01

    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...

  18. Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

    Directory of Open Access Journals (Sweden)

    Simon R O Nilsson

    Full Text Available Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS-, in a T- or Y-maze configuration. This was followed by three conditions; (1 Full reversal, where contingencies reversed; (2 Perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3 Learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss

  19. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    Science.gov (United States)

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    substrate G6P that is a direct product of HK II. 3-bromopyruvate (3BP, inhibitor of HK II) may prove as a promising anticancer and antimetastatic agent based on antagonizing the Warburg effect and disturbing the malignant behavior in cancer cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. SIRT1 deacetylates RFX5 and antagonizes repression of collagen type I (COL1A2) transcription in smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Jun [Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University (China); Department of Respiratory Medicine, Jiangsu Provincial Hospital of Chinese Traditional Medicine (China); Wu, Xiaoyan; Yang, Yuyu; Zhao, Yuhao [Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University (China); Fang, Mingming [Jiangsu Jiankang Vocational Institute (China); Xie, Weiping, E-mail: wpxienjmu@gmail.com [Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University (China); Wang, Hong, E-mail: hwangnjmu@gmail.com [Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University (China); Xu, Yong [Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer SIRT1 interacts with and deacetylates RFX5. Black-Right-Pointing-Pointer SIRT1 activation attenuates whereas SIRT1 inhibition enhances collagen repression by RFX5 in vascular smooth muscle cells. Black-Right-Pointing-Pointer SIRT1 promotes cytoplasmic localization and proteasomal degradation of RFX5 and cripples promoter recruitment of RFX5. Black-Right-Pointing-Pointer IFN-{gamma} represses SIRT1 expression in vascular smooth muscle cells. Black-Right-Pointing-Pointer SIRT1 agonist alleviates collagen repression by IFN-{gamma} in vascular smooth muscle cells. -- Abstract: Decreased expression of collagen by vascular smooth muscle cells (SMCs) within the atherosclerotic plaque contributes to the thinning of the fibrous cap and poses a great threat to plaque rupture. Elucidation of the mechanism underlying repressed collagen type I (COL1A2) gene would potentially provide novel solutions that can prevent rupture-induced complications. We have previously shown that regulatory factor for X-box (RFX5) binds to the COL1A2 transcription start site and represses its transcription. Here we report that SIRT1, an NAD-dependent, class III deacetylase, forms a complex with RFX5. Over-expression of SIRT1 or NAMPT, which synthesizes NAD+ to activate SIRT1, or treatment with the SIRT1 agonist resveratrol decreases RFX5 acetylation and disrupts repression of the COL1A2 promoter activity by RFX5. On the contrary, knockdown of SIRT1 or treatment with SIRT1 inhibitors induces RFX5 acetylation and enhances the repression of collagen transcription. SIRT1 antagonizes RFX5 activity by promoting its nuclear expulsion and proteasomal degradation hence dampening its binding to the COL1A2 promoter. The pro-inflammatory cytokine IFN-{gamma} represses COL1A2 transcription by down-regulating SIRT1 expression in SMCs. Therefore, our data have identified as novel pathway whereby SIRT1 maintains collagen synthesis in SMCs by modulating RFX5 activity.

  1. Persistent escalation of alcohol consumption by mice exposed to brief episodes of social defeat stress: suppression by CRF-R1 antagonism.

    Science.gov (United States)

    Newman, Emily L; Albrechet-Souza, Lucas; Andrew, Peter M; Auld, John G; Burk, Kelly C; Hwa, Lara S; Zhang, Eric Y; DeBold, Joseph F; Miczek, Klaus A

    2018-06-01

    Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify

  2. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress.

    Science.gov (United States)

    Deng, Yan; Guo, Xue-Ling; Yuan, Xiao; Shang, Jin; Zhu, Die; Liu, Hui-Guo

    2015-08-20

    The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves. Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method. The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits. The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  3. The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dowejko, Albert, E-mail: Albert.Dowejko@klinik.uni-regensburg.de [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Bauer, Richard; Bauer, Karin [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Mueller-Richter, Urs D.A. [Department of Oral and Maxillofacial Plastic Surgery, University of Wuerzburg, Pleicherwall 2, 97070 Wuerzburg (Germany); Reichert, Torsten E. [Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany)

    2012-03-10

    antagonizes Wnt-mediated cell proliferation through interaction with major cell cycle factors. Black-Right-Pointing-Pointer Modulating HECA level confers benefits for engaging tumor cells with cisplatin.

  4. Extract of Kuding tea prevents high-fat diet-induced metabolic disorders in C57BL/6 mice via liver X receptor (LXR β antagonism.

    Directory of Open Access Journals (Sweden)

    Shengjie Fan

    Full Text Available To investigate the effects of ilex kudingcha C. J. Tseng (kuding tea, a traditional beverage in China, on the metabolic disorders in C57BL/6 mice induced by high-fat diets.For the preventive experiment, the female C57BL/6 mice were fed with a standard diet (Chow, high-fat diet (HF, and high-fat diet mixed with 0.05% ethanol extract of kuding tea (EK for 5 weeks. For the therapeutic experiment, the C57BL/6 mice were fed high-fat diet for 3 months, and then mice were split and EK was given with oral gavages for 2 weeks at 50 mg/day/kg. Body weight and daily food intake amounts were measured. At the end of treatment, the adipocyte images were assayed with a scanning electron microscope, and the fasting blood glucose, glucose tolerance test, serum lipid profile and lipids in the livers were analyzed. A reporter gene assay system was used to test the whether EK could act on nuclear receptor transcription factors, and the gene expression analysis was performed with a quantitative PCR assay.In the preventive treatment, EK blocked the body weight gain, reduced the size of the adipocytes, lowered serum triglyceride, cholesterol, LDL-cholesterol, fasting blood glucose levels and glucose tolerance in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, EK reduced the size of the white adipocytes, serum TG and fasting blood glucose levels in obese mice. With the reporter assay, EK inhibited LXRβ transactivity and mRNA expression of LXRβ target genes.We observed that EK has both preventive and therapeutic roles in metabolic disorders in mice induced with high-fat diets. The effects appear to be mediated through the antagonism of LXRβ transactivity. Our data indicate that kuding tea is a useful dietary therapy and a potential source for the development of novel anti-obesity and lipid lowering drugs.

  5. Orexin 1 and orexin 2 receptor antagonism in the basolateral amygdala modulate long-term potentiation of the population spike in the perforant path-dentate gyrus-evoked field potential in rats.

    Science.gov (United States)

    Ardeshiri, Motahareh Rouhi; Hosseinmardi, Narges; Akbari, Esmaeil

    2018-03-01

    Involvement of amygdalo-hippocampal substructures in patients with narcolepsy due to deficiencies in the orexinergic system, and the presence of hippocampus-dependent memory impairments in this disorder, have led us to investigate the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. We used a 200-Hz high-frequency stimulation protocol in anesthetized rats. We studied the long-term synaptic plasticity of perforant path-dentate gyrus granule cells following the inactivation of orexin receptors before and after tetanic stimulation. LTP of the DG population spike was attenuated in the presence of orexin 1 and 2 receptor antagonism (treatment with SB-334867-A and TCS-OX2-29, respectively) in the BLA when compared to that observed following treatment with dimethyl sulfoxide (DMSO). However, the population excitatory post-synaptic potentials were not affected. Moreover, when orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups. Our findings suggest that the orexinergic system of the BLA plays a modulatory role in the regulation of hippocampal plasticity in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. 1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl, 3-F-BPAP, antagonizes the enhancer effect of (-)-BPAP in the shuttle box and leaves the effect of (-)-deprenyl unchanged.

    Science.gov (United States)

    Knoll, Joseph; Miklya, Ildikó; Knoll, Berta; Yasusa, Takuya; Shimazu, Seiichiro; Yoneda, Fumio

    2002-09-13

    The subcutaneous administration of 1 mg/kg tetrabenazine, once daily for 5 days, which depletes the catecholamine stores in the brain, significantly inhibits in rats the acquisition of a two-way conditioned avoidance reflex in the shuttle box. Enhancer substances, the tryptamine-derived selective and highly potent enhancer, R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane HCl [(-)-BPAP] (0.05-10 mg/kg), the beta-phenylethylamine (PEA)-derived enhancer, (-)-deprenyl (1-5 mg/kg) and the (-)-deprenyl analogue, free of MAO-B inhibitory potency, (-)-1-phenyl-2-propylaminopentane HCl [(-)-PPAP], (1-5 mg/kg), antagonize in a dose-dependent manner the inhibition of learning caused by tetrabenazine. 1-(Benzofuran 2 yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl [3 F BPAP], a newly synthetized analogue of (-)-BPAP with low specific activity, significantly antagonized the enhancer effect of (-)-BPAP but left the effect of (-)-deprenyl and (-)-PPAP unchanged. This is the first proof for a difference in the mechanism of action between a PEA-derived enhancer substance and its tryptamine-derived peer.

  7. NMDA receptor antagonism by repetitive MK801 administration induces schizophrenia-like structural changes in the rat brain as revealed by voxel-based morphometry and diffusion tensor imaging.

    Science.gov (United States)

    Wu, H; Wang, X; Gao, Y; Lin, F; Song, T; Zou, Y; Xu, L; Lei, H

    2016-05-13

    Animal models of N-methyl-d-aspartate receptor (NMDAR) antagonism have been widely used for schizophrenia research. Less is known whether these models are associated with macroscopic brain structural changes that resemble those in clinical schizophrenia. Magnetic resonance imaging (MRI) was used to measure brain structural changes in rats subjected to repeated administration of MK801 in a regimen (daily dose of 0.2mg/kg for 14 consecutive days) known to be able to induce schizophrenia-like cognitive impairments. Voxel-based morphometry (VBM) revealed significant gray matter (GM) atrophy in the hippocampus, ventral striatum (vStr) and cortex. Diffusion tensor imaging (DTI) demonstrated microstructural impairments in the corpus callosum (cc). Histopathological results corroborated the MRI findings. Treatment-induced behavioral abnormalities were not measured such that correlation between the brain structural changes observed and schizophrenia-like behaviors could not be established. Chronic MK801 administration induces MRI-observable brain structural changes that are comparable to those observed in schizophrenia patients, supporting the notion that NMDAR hypofunction contributes to the pathology of schizophrenia. Imaging-derived brain structural changes in animal models of NMDAR antagonism may be useful measurements for studying the effects of treatments and interventions targeting schizophrenia. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses.

    Science.gov (United States)

    Aydillo, Teresa; Ayllon, Juan; Pavlisin, Amzie; Martinez-Romero, Carles; Tripathi, Shashank; Mena, Ignacio; Moreira-Soto, Andrés; Vicente-Santos, Amanda; Corrales-Aguilar, Eugenia; Schwemmle, Martin; García-Sastre, Adolfo

    2018-04-01

    Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 -/- human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique

  9. Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

    Science.gov (United States)

    Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

    2017-08-01

    Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common

  10. Comparison of the effects of taurine and magnesium on electrical characteristics of artificial and natural membranes. V. Study on the human amnion of the antagonism between magnesium, taurine and polluting metals

    Energy Technology Data Exchange (ETDEWEB)

    Bara, M.; Guiet-Bara, A.; Durlach, J.

    1985-01-01

    The effects of metal pollutants (Pb, Cd, Hg, As) were studied on strips of human amnion isolated from the placental zone put in between two Ussing chambers with Hanks' solution at 37 degrees C and pH 7.4. The total conductance Gt through the human isolated amnion was decreased on the fetal side by Pb and As; on the maternal side by Cd, Hg and As. When Gt was decreased by metal pollutants, Mg or taurine (TA) were added in the external medium to induce an antagonism between Mg or TA and metal pollutants. The addition of Mg increased significantly the Gt reduced by Pb, Cd and Hg, but had no effect on the Gt reduced by As. The addition of taurine increased significantly the Gt reduced by Cd and Hg, but had no effect on the Gt reduced by Pb and As. Dixon's kinetics (Gt as a function of the Mg or TA concentration when the metal pollutant concentration increased) indicate that there is a competitive inhibition between Mg-Pb and Mg-Cd (the inhibition constant Ki is lower with Pb (= 2.5) than with Cd (= 11.4) and suggests a greater antagonism between Mg-Pb than between Mg-Cd). Moreover, there appears to be a noncompetitive inhibition between Mg-Hg, TA-Cd and TA-Hg. These results indicate that Mg and TA, on the fetal side, exert an action on the same sites and that, on the maternal side, their action takes place on the same sites and also on different ones. Also, TA can be considered as a partial magnesium agonist, at least in the human amnion.

  11. Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

    Science.gov (United States)

    Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

    2018-01-01

    Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Disappearance of the last lions and hyenas of Europe in the Late Quaternary - a chain reaction of large mammal prey migration, extinction and human antagonism

    Science.gov (United States)

    Diedrich, Cajus G.

    2010-05-01

    , Harz Mountain Karst) such as humans (archaeology cf. Günther 1988) but there are also lacking radiocarbon dating series or new excavations. Humans must have been in antagonism to the large predators about their prey and also their Late Palaeolithic sanctuaries - the large caves especially in southern Europe, in which they left thousands of animal figurations mainly during the Gravettian to Late Magdalenian periods (e.g. Breuil 1952, Begouen and Clottes 1987, Chauvet et al. 1995). Therefore the extinction reason of the largest predators of the Late Quaternary seems to be a complex combination of climate change with resulting maximum glacier extension which finally caused a southern directed megafaunal migration and reduction of the available caves and habitat areas in general. Finally in those southern European regions a higher competition about larger caves as cave bear hibernation places, hyena den sites and human settlement/sanctuary sites must have happened. Therefore an active hunt onto lions and hyenas can not be excluded nor be proven well yet, even if there are finds of necklesses in Europe from Late Palaeolithic ages made of mainly carnivore teeth including rare lion and hyena teeth, which might have been only collected. The resettlement of the northern European region by humans and a reduced "reindeer fauna" and its main and largest predators such as wolves and wolverines after the maximum glacier extension in the middle Late Weichselian started not before the Late Magdalenian (Magdalénian V: e.g. Perick Caves, Martins Cave - Sauerland Karst; Rübeland Caves - Harz Mountain Karst, Teufelsbrücke stone arch - Thuringian Karst). Humans occupied at that post-maximum glaciation time many caves in the Sauerland Karst region and even at open air sites in the Münsterland Bay or central Germany (cf. Bosinski 1987, Günther 1988). Within this Late Magdalénian V-VI times in the record of ten thousands of bones from more then 100 sites no hyena or lion remains are

  13. La pastora y el cóndor: de los antagonismos entre naturaleza y cultura a los antagonismos de género; A pastora e o condor: desde os antagonismos entre natureza e cultura para os antagonismos de gênero; The shepherdess and the condor: from the antagonisms between nature and culture to gender antagonisms

    Directory of Open Access Journals (Sweden)

    Graciela Hernández

    2018-01-01

    of cooking and from feeding only on raw meat. It seems that this conflict inexorably recalls the theories about raw and cooked in structuralism; however, we are going to take another reading of the chosen text, derived from the analysis made by the female workshop participants. It is a qualitative ethnographic work in a workshop on oral history in adults’ primary education, in an area of onion production and migration from Bolivia to the south-east of Buenos Aires province, in Argentina. The main conclusion we have reached is that we could see as this tale depicts the condor as an emblem of the authoritative man and it was the starting point to talk about gender antagonisms and to discuss about subjective experiences on affective and sexual rights of the women. Keywords: Narrative, Ethnography, Gender, Feminisms, Memory.

  14. Evaluación in vitro de Microorganismos Nativos por su Antagonismo contra Moniliophthora roreri Cif & Par en Cacao (Theobroma cacao L. In vitro evaluation of Native Microorganisms for their Antagonism against Moniliophthora roreri Cif & Parin Cocoa (Theobroma cacao L.

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Villamil Carvajal

    2012-06-01

    Full Text Available Resumen. La moniliasis, causada por Moniliophthora roreri Cif & Par, se ha convertido en la principal enfermedad limitante de la producción de cacao en Colombia y otros países. Con el objetivo de explorar alternativas para el biocontrol de esta enfermedad, hongos y bacterias aislados de frutos y suelo rizosférico de lotes plantados con cacao fueron evaluados por su antagonismo contra M. roreri. La evaluación se realizó en cajas Petri con PDA, para lo cual se colocó en el centro de las mismas, un disco de 5 mm de diámetro colonizado por el patógeno y a 3 cm del borde, sobre los ejes horizontal y vertical, cada uno de los aislamientos. Los microorganismos nativos que inicialmente mostraron antagonismo fueron posteriormente evaluados in vitro por su capacidad de restringir el crecimiento y esporulación de M. roreri. Los resultados indicaron que de 53 aislamientos de frutos y suelo rizosférico, 7 mostraron antagonismo contra M. roreri y entre ellos los más efectivos fueron los hongos H5 y H20 y la bacteria B3, los hongos para la restricción tanto del crecimiento como de la esporulación y la bacteria para el crecimiento. El hongo H20 inhibió en su totalidad el crecimiento de M. roreri. Estos resultados hacen posible que estos aislamientos sean promisorios para su incorporación al manejo de la enfermedad bajo condiciones de campo. De acuerdo con la caracterización morfológica y las pruebas bioquímicas los hongos pertenecen al género Trichoderma y la bacteria al género Bacillus.Abstract. The moniliasis, caused by Moniliophthora roreri Cif & Par, has become the principal disease limiting cocoa production in Colombia and other countries. With the objective of exploring alternatives for the biocontrol of this disease, fungi and bacteria isolated from cocoa fruits and rhizospheric soil from plots planted to cocoa trees were evaluated for their antagonism against M. roreri. The evaluation was conducted in Petri dishes containing PDA, by

  15. The selective antagonism of P2X7 and P2Y1 receptors prevents synaptic failure and affects cell proliferation induced by oxygen and glucose deprivation in rat dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Giovanna Maraula

    Full Text Available Purinergic P2X and P2Y receptors are broadly expressed on both neurons and glial cells in the central nervous system (CNS, including dentate gyrus (DG. The aim of this research was to determine the synaptic and proliferative response of the DG to severe oxygen and glucose deprivation (OGD in acute rat hippocampal slices and to investigate the contribution of P2X7 and P2Y1 receptor antagonism to recovery of synaptic activity after OGD. Extracellular field excitatory post-synaptic potentials (fEPSPs in granule cells of the DG were recorded from rat hippocampal slices. Nine-min OGD elicited an irreversible loss of fEPSP and was invariably followed by the appearance of anoxic depolarization (AD. Application of MRS2179 (selective antagonist of P2Y1 receptor and BBG (selective antagonist of P2X7 receptor, before and during OGD, prevented AD appearance and allowed a significant recovery of neurotransmission after 9-min OGD. The effects of 9-min OGD on proliferation and maturation of cells localized in the subgranular zone (SGZ of slices prepared from rats treated with 5-Bromo-2'-deoxyuridine (BrdU were investigated. Slices were further incubated with an immature neuron marker, doublecortin (DCX. The number of BrdU+ cells in the SGZ was significantly decreased 6 hours after OGD. This effect was antagonized by BBG, but not by MRS2179. Twenty-four hours after 9-min OGD, the number of BrdU+ cells returned to control values and a significant increase of DCX immunofluorescence was observed. This phenomenon was still evident when BBG, but not MRS2179, was applied during OGD. Furthermore, the P2Y1 antagonist reduced the number of BrdU+ cells at this time. The data demonstrate that P2X7 and P2Y1 activation contributes to early damage induced by OGD in the DG. At later stages after the insult, P2Y1 receptors might play an additional and different role in promoting cell proliferation and maturation in the DG.

  16. Comparison of effects of angiotensin-converting enzyme inhibition with those of angiotensin II receptor antagonism on functional and metabolic recovery in postischemic working rat heart as studied by [31P] nuclear magnetic resonance.

    Science.gov (United States)

    Werrmann, J G; Cohen, S M

    1994-10-01

    To assess the role of angiotensin II (AII) in development of myocardial injury during ischemia and reperfusion, the effects of short-term treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the effects of short-term treatment with L-158,338, an AII antagonist, in isolated working rat heart. Myocardial function was assessed and correlated with simultaneous measurement of high-energy phosphate metabolism and intracellular pH by [31P] nuclear magnetic resonance (NMR) before, during, and after global ischemia. Hearts from rats treated with 1 mg/kg lisinopril in vivo recovered substantially more function than those of controls (p effect on functional recovery. A dose-dependent increase in functional recovery was observed in rat heart treated with 0.3, 1, or 3 mg/kg L-158,338 in vivo (p energy phosphate metabolism was essentially unchanged by any treatment regimen. AII antagonism alone resulted in a degree of improvement in functional recovery comparable to that observed with oral ACE inhibitor treatment.

  17. The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

    Science.gov (United States)

    Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

    2017-07-25

    Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

  18. CGRP-receptor antagonism in migraine treatment

    DEFF Research Database (Denmark)

    Edvinsson, Lars; Petersen, Kenneth Ahrend

    2007-01-01

    Primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. Associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association...... between the headache and the release of calcitonin gene-related peptide (CGRP) but not with other neuronal messengers. The specific purpose of this review is to describe CGRP in the human cranial circulation and to elucidate a possible role for a specific antagonist in the treatment of primary headaches...... nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists, which would predictably have less cardiovascular side effects as compared to the triptans. The initial pharmacological profile of such a group of compounds has...

  19. Quorum sensing antagonism from marine organisms

    DEFF Research Database (Denmark)

    Skindersø, Mette Elena; Ettinger-Epstein, P.; Rasmussen, Thomas Bovbjerg

    2008-01-01

    target for the control of infectious bacteria. We present the results of screening of 284 extracts of marine organisms from the Great Barrier Reef, Australia, for their inhibition of QS. Of the 284 extracts, 64 (23%) were active in a general, LuxR-derived QS screen, and of these 36 (56%) were also active...... in a specific Pseudomonas aeruginosa QS screen. Extracts of the marine sponge Luffariella variabilis proved active in both systems. The secondary metabolites manoalide, manoalide monoacetate, and secomanoalide isolated from the sponge showed strong QS inhibition of a lasB::gfp(ASV) fusion, demonstrating...... the potential for further identification of specific QS antagonists from marine organisms....

  20. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

    Science.gov (United States)

    Hubers, Scott A.; Brown, Nancy J.

    2016-01-01

    Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA approved the first of a new class of drugs for the treatment of heart failure; valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

  1. Photo-antagonism of the GABAA receptor.

    Science.gov (United States)

    Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

    2014-07-29

    Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

  2. Prostaglandins and prostaglandin receptor antagonism in migraine

    DEFF Research Database (Denmark)

    Antonova, Maria

    2013-01-01

    Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20....... The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra......-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis...

  3. Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

    Science.gov (United States)

    Deng, Ziqing; Shan, Yue; Pan, Qing; Gao, Xiang; Yan, Aixin

    2013-01-01

    The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of Escherichia coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF in the operon has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798 bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full-length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

  4. Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression

    Directory of Open Access Journals (Sweden)

    Ziqing eDeng

    2013-07-01

    Full Text Available The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of E. coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.

  5. Memantine, a Low-Affinity NMDA Receptor Antagonist, Protects against Methylmercury-Induced Cytotoxicity of Rat Primary Cultured Cortical Neurons, Involvement of Ca2+ Dyshomeostasis Antagonism, and Indirect Antioxidation Effects.

    Science.gov (United States)

    Liu, Wei; Xu, Zhaofa; Yang, Tianyao; Xu, Bin; Deng, Yu; Feng, Shu

    2017-09-01

    Methylmercury (MeHg) is an extremely dangerous environmental pollutant that induces severe toxic effects in the central nervous system. Neuronal damage plays critical roles mediating MeHg-induced loss of brain function and neurotoxicity. The molecular mechanisms of MeHg neurotoxicity are incompletely understood. The objective of the study is to explore mechanisms that contribute to MeHg-induced neurocyte injuries focusing on neuronal Ca 2+ dyshomeostasis and alteration of N-methyl-D-aspartate receptors (NMDARs) expression, as well as oxidative stress in primary cultured cortical neurons. In addition, the neuroprotective effects of memantine against MeHg cytotoxicity were also investigated. The cortical neurons were exposed to 0, 0.01, 0.1, 1, or 2 μM methylmercury chloride (MeHgCl) for 0.5-12 h, or pre-treated with 2.5, 5, 10, or 20 μM memantine for 0.5-6 h, respectively; cell viability and LDH release were then quantified. For further experiments, 2.5, 5, and 10 μM of memantine pre-treatment for 3 h followed by 1 μM MeHgCl for 6 h were performed for evaluation of neuronal injuries, specifically addressing apoptosis; intracellular free Ca 2+ concentrations; ATPase activities; calpain activities; expressions of NMDAR subunits (NR1, NR2A, NR2B); NPSH levels; and ROS formation. Exposure of MeHgCl resulted in toxicity of cortical neurons, which were shown as a loss of cell viability, high levels of LDH release, morphological changes, and cell apoptosis. Moreover, intracellular Ca 2+ dyshomeostasis, ATPase activities inhibition, calpain activities, and NMDARs expression alteration were observed with 1 μM MeHgCl administration. Last but not least, NPSH depletion and reactive oxygen species (ROS) overproduction showed an obvious oxidative stress in neurons. However, memantine pre-treatment dose-dependently antagonized MeHg-induced neuronal toxic effects, apoptosis, Ca 2+ dyshomeostasis, NMDARs expression alteration, and oxidative stress. In conclusion, the

  6. 78 FR 14540 - Cyromazine, Silica Silicates (Silica Dioxide and Silica Gel), Glufosinate Ammonium, Dioctyl...

    Science.gov (United States)

    2013-03-06

    ... variety of agricultural food crop as well as non-food uses such as landscape and greenhouse ornamentals... film covering their bodies which normally prevents the loss of water, leading to death by desiccation...

  7. Antagonism of Trichoderma species on Cladosporium herbarum and their enzimatic characterization Antagonismo de espécies de Trichoderma sobre Cladosporium herbarum e suas caracterização enzimática

    Directory of Open Access Journals (Sweden)

    Maria Angélica G. Barbosa

    2001-06-01

    Full Text Available The verrucose caused by Cladosporium herbarum reduces production and quality of Passion fruit (Passiflora edulis Sims., a largely consumed tropical fruit. This work aimed to investigate the antagonism of Trichoderma species (T. polysporum, T. koningii, T. viride and T. harzianum against Cladosporium herbarum, and to study the production of extracellular hydrolytic enzymes by the pathogen and the antagonists. The results showed considerable antagonistic potential for the biocontrol of C. herbarum isolates by all Trichoderma species, except T. koningii. The most distinguished effect was observed for T. polysporum. In relation to the pattern of esterase obtained by electrophoresis in poliacrylamyde gel, the major activity presented by the isolates was observed after five days of incubation. The C. herbarum isolates produced extracellular enzymes, lipase, pectinase, cellulase, and protease, all possibly related to the infection process. Amylase excretion, not known to be associated with phytopathogens, was detected in Trichoderma species, but not in C. herbarum. In addition to amylase, all Trichoderma species tested produced also extracellular cellulase and pectinase, except T. koningii in relation to the latter enzyme. The demonstration of various esterase isoenzymes in zymograms of the Trichoderma species and C. herbarum isolates was markedly improved by washing the mycelia with detergents or EDTA. This fact suggested that a major fraction of extracelular enzymes may remain attached to outside fungal cell wall after being excreted.O maracujá (Passiflora edulis Sims., um fruto tropical amplamente consumido, tem sua produção e a qualidade dos seus frutos reduzidos pela verrugose causada por Cladosporium herbarum. Este trabalho objetivou investigar o antagonismo de espécies de Trichoderma (T. polysporum, T.koningii, T. viride e T. harzianum contra C. herbarum, e estudar a produção de enzimas hidrolíticas extracelulares pelo fitopatógeno e

  8. Removal of Pesticides and Inorganic Contaminants in Anaerobic and Aerobic Biological Contactors

    Science.gov (United States)

    This presentation contains data on the removal of pesticides (acetochlor, clethodim, dicrotophos), ammonia, nitrate, bromate and perchlorate through aerobic and anaerobic biological treatment processes.

  9. Manejo de capim pé-de-galinha em lavouras de soja transgênica resistente ao glifosato Management of goose grass on transgenic soybean, resistant to glyphosate

    Directory of Open Access Journals (Sweden)

    André da Rosa Ulguim

    2013-01-01

    Full Text Available O objetivo deste trabalho foi avaliar a resistência de capim pé-de-galinha (Eleusine indica ao glifosato, em lavouras de soja transgênica; avaliar o efeito de aplicações de glifosato em diferentes estádios de desenvolvimento; identificar práticas agronômicas associadas à seleção de biótipos resistentes; e avaliar a eficiência dos herbicidas cletodim, fluazifope-P-butílico, clomazona, glufosinato de amônio e glifosato nas plantas resistentes. Plantas escapes ao tratamento com glifosato foram coletadas em 24 propriedades, no Rio Grande do Sul. As plantas foram cultivadas em casa de vegetação, tendo-se avaliado a sua resistência ao glifosato. Os acessos resistentes foram selecionados e avaliados quanto ao efeito da aplicação do glifosato em diferentes estádios de crescimento e quanto à sensibilidade aos herbicidas. Foi aplicado um questionário aos produtores para identificação das práticas agronômicas associadas às falhas no controle. O controle de E. indica pelo glifosato é mais efetivo com a aplicação em estádios iniciais de desenvolvimento. Práticas agronômicas, como uso contínuo de baixas doses do herbicida, aplicação em estádios de desenvolvimento avançados das plantas daninhas (mais de um afilho e a ausência de rotação de culturas foram relacionadas às falhas de controle observadas. Os herbicidas cletodim, fluazifope-P-butílico e glufosinato de amônio são alternativas eficientes para o controle de E. indica.The objective of this work was to evaluate the resistance of goose grass (Eleusine indica to glyphosate application in transgenic soybean crops; evaluate the effect of glyphosate applications in different growth stages; identify the main agronomic practices associated with the selection of resistant biotypes; and evaluate the effect of the herbicides clethodim, fluazifop-p-butyl, clomazone, glufosinate ammonium, and glyphosate on resistant plants. Plants that survived glyphosate application

  10. Antagonism of Procyanidins on Semicarbazide- induced Reproductive Toxicity in Male Mice%原花青素对氨基脲致雄性小鼠生殖毒性的拮抗作用

    Institute of Scientific and Technical Information of China (English)

    朱乐玫; 袁萍; 张贝贝; 王维芬; 凌娅; 文静; 李东阳

    2012-01-01

    Objective To observe the antagonism and its mechanism of procyanidins (PC) on semicarbazide (SEM) caused reproductive toxicity in male mice. Methods Fifty KM male mice were randomly divided into 5 groups: solvent control group, SEM exposure group, low- , medium- and high- dose PC protection groups. The mice of solvent control group were administrated intragastrically with deionized water. The mice of SEM exposure group were administered intragastrically with 56.25 mg/kg. Bw SEM solution in the first two weeks, and then were dosed by gavage with deionized water for 4 weeks. The mice of three doses groups were fed with PC 100, 200 and 400 mg/kg. Bw separately in the first four weeks, and then fed with the same dose of SEM solution for the next two weeks separately. All animals in each group received intragastric administra-tion once a day according to 10 ml/kg, bw volume. After 6 - week oral administration, the mice were sacrificed and the reproductive related indicators of blood, tissues and organs were detected. Results Testicular morphology in PC protection group was improved compared with SEM exposure group, and the improving effect was more obvious with the increasing dose of PC. Compared with SEM exposure group, sperm count and activity of the mice in low- , medium- and high- dose PC groups were increased significantly, while the malformation rates were decreased. Serum levels of T, LH, and FSH in the three doses groupswere all higher than those of SEM exposure group. Compared with SEM exposure group, SOD and GSH - PX activity of the three doses groups increased, while MDA and GSH content decreased, and the difference was statistically significant (P<0.05). Conclusions The addition of proper amount of PC has protection effects on the reproductive system of sub - chronic injury in male mice. Antioxidation is an important mechanism of PC in protecting from SEM - induced reproductive damage.%目的 观察原花青素(PC)对氨基脲(SEM)致雄性小鼠生殖毒

  11. Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone.

    Directory of Open Access Journals (Sweden)

    Stephen R Morairty

    Full Text Available The hypocretin (orexin system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1 and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867 and HCRTR2 (EMPA antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat. All 4 antagonists bound to their respective receptors with high affinity and selectivity in vitro. Since in vivo pharmacokinetic experiments revealed poor brain penetration for SB-408124, SB-334867 was selected for subsequent in vivo studies. When injected in the mid-active phase, SB-334867 produced small increases in rapid-eye-movement (REM and non-REM (NR sleep. EMPA produced a significant increase in NR only at the highest dose studied. In contrast, almorexant decreased NR latency and increased both NR and REM proportionally throughout the subsequent 6 h without rebound wakefulness. The increased NR was due to a greater number of NR bouts; NR bout duration was unchanged. At the highest dose tested (100 mg/kg, almorexant fragmented sleep architecture by increasing the number of waking and REM bouts. No evidence of cataplexy was observed. HCRTR1 occupancy by almorexant declined 4-6 h post-administration while HCRTR2 occupancy was still elevated after 12 h, revealing a complex relationship between occupancy of HCRT receptors and sleep promotion. We conclude that dual HCRTR1/R2 blockade is more effective in promoting sleep than blockade of either HCRTR alone. In contrast to GABA receptor agonists which induce sleep by generalized inhibition, HCRTR antagonists seem to facilitate sleep by reducing waking "drive".

  12. Identificação de biótipos de azevém (Lolium multiflorum resistentes ao herbicida glyphosate em pomares de maçã Identification of glyphosate-resistant ryegrass (Lolium multiflorum biotypes in apple orchards

    Directory of Open Access Journals (Sweden)

    L. Vargas

    2004-12-01

    Full Text Available O glyphosate é um herbicida de amplo espectro utilizado há mais de 15 anos em pomares de maçã na região de Vacaria-RS, para manejo da vegetação nas linhas da cultura. São realizadas, em geral, três a quatro aplicações por ciclo e a dose normalmente utilizada é de 720 a 1.080 g e.a. ha-1 de glyphosate (2 a 3 L ha-1 do produto comercial. O azevém (Lolium multiflorum é uma planta daninha comum em pomares e, tradicionalmente, sensível ao glyphosate. Entretanto, nos últimos anos a ocorrência de plantas de azevém que, após receberem o tratamento com glyphosate, não manifestam sintomas significativos de toxicidade sugere que elas adquiriram resistência ao produto. Assim, com o objetivo de avaliar a resposta de uma população de plantas de azevém ao glyphosate, foram realizados três experimentos: um em campo e dois em casa de vegetação. No experimento em campo os tratamentos avaliados constaram de doses crescentes de glyphosate (0, 360, 720, 1.440, 2.880, 5.760 e 11.520 g e.a. ha-1, e os herbicidas paraquat, glufosinate, haloxyfop e diclofop foram empregados como produtos-padrão, aplicados em dois estádios vegetativos do azevém. No experimento em casa de vegetação, os tratamentos constaram de doses crescentes de glyphosate (0, 360, 720, 1.440, 2.880 e 5.760 g e.a. ha-1 mais os herbicidas testemunhas, aplicados sobre plantas do biótipo considerado resistente e de um sensível. No segundo experimento realizado em casa de vegetação foram avaliados tratamentos contendo glyphosate (720, 1.440, 2.880, 720 + 720 e 720 + 1.440 g e.a. ha-1, em aplicações únicas e seqüenciais, mais os herbicidas paraquat, glufosinate, haloxyfop, clethodim, sethoxydim, diclofop, fenoxaprop, fluazifop, paraquat + diuron, atrazine + simazine, trifluralin e metolachlor. A toxicidade dos tratamentos herbicidas foi avaliada aos 15, 30 e 45 DAT (dias após tratamento. Os resultados obtidos nos experimentos em campo e em casa de vegetação, de forma

  13. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    Science.gov (United States)

    Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

    2016-01-01

    Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

  14. In vitro antagonism of Thielaviopsis paradoxa by Trichoderma longibrachiatum.

    Science.gov (United States)

    Sánchez, Vladimir; Rebolledo, Oscar; Picaso, Rosa M; Cárdenas, Elizabeth; Córdova, Jesús; González, Orfil; Samuels, Gary J

    2007-01-01

    Seventy-nine Trichoderma strains were isolated from soil taken from 28 commercial plantations of Agave tequilana cv. 'Azul' in the State of Jalisco, Mexico. Nine of these isolates produced nonvolatile metabolites that completely inhibited the growth of Thielaviopsis paradoxa on potato dextrose agar plates. These isolates were identified as Trichoderma longibrachiatum on the basis of their morphology and DNA sequence analysis of two genes (ITS rDNA and translation elongation factor EF-1alpha). Mycoparasitism of Th. paradoxa by T. longibrachiatum strains in dual cultures was examined by scanning electron microscopy. The Trichoderma hyphae grew alongside the Th. paradoxa hyphae, but penetration of Thielaviopsis hyphae by Trichoderma was no apparent. Aleurioconidia of Th. paradoxa were parasitized by Trichoderma. Both hyphae and aleurioconidia of Th. paradoxa lost turgor pressure, wrinkled, collapsed and finally disintegrated. In liquid cultures, all nine Trichoderma isolates produced proteases, beta-1,3-glucanases and chitinases that would be responsible for the degradation of Thielaviopsis hyphae. These results demonstrate that the modes of action of T. longibrachiatum involved against Th. paradoxa in vitro experiments are mycoparasitism and the production of nonvolatile toxic metabolites.

  15. Pathogen self defense: mechanisms to counteract microbial antagonism

    NARCIS (Netherlands)

    Duffy, B.K.; Schouten, A.; Raaijmakers, J.M.

    2003-01-01

    Natural and agricultural ecosystems harbor a wide variety of microorganisms that play an integral role in plant health, crop productivity, and preservation of multiple ecosystem functions. Interactions within and among microbial communities are numerous and range from synergistic and mutualistic to

  16. Cooperation, trust, and antagonism: How public goods are promoted

    NARCIS (Netherlands)

    Parks, C.D.; Joireman, J.; van Lange, P.A.M.

    2013-01-01

    One of the most continually vexing problems in society is the variability with which citizens support endeavors that are designed to help a great number of people. In this article, we examine the twin roles of cooperative and antagonistic behavior in this variability. We find that each plays an

  17. Antagonism in the carbon footprint between beef and dairy ...

    African Journals Online (AJOL)

    GScholtz

    2014-08-22

    Aug 22, 2014 ... of manure is aerobic, which produces carbon dioxide (CO2), part of which is absorbed .... (2013) estimated the methane emission factor for dairy cattle on a TMR to be 76.4 kg ... Capper, J.L., Cady, R.A. & Bauman, D.E., 2009.

  18. Nubbin isoform antagonism governs Drosophila intestinal immune homeostasis.

    Directory of Open Access Journals (Sweden)

    Bo G Lindberg

    2018-03-01

    Full Text Available Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila. Global transcriptional profiling of adult flies overexpressing Nub-PB in immunocompetent tissues revealed that this form is a strong transcriptional activator of a large set of immune genes. Further genetic analyses showed that Nub-PB is sufficient to drive expression both independently and in conjunction with nuclear factor kappa B (NF-κB, JNK and JAK/STAT pathways. Similar overexpression of Nub-PD did, conversely, repress expression of the same targets. Strikingly, isoform co-overexpression normalized immune gene transcription, suggesting antagonistic activities. RNAi-mediated knockdown of individual nub transcripts in enterocytes confirmed antagonistic regulation by the two isoforms and that both are necessary for normal immune gene transcription in the midgut. Furthermore, enterocyte-specific Nub-PB expression levels had a strong impact on gut bacterial load as well as host lifespan. Overexpression of Nub-PB enhanced bacterial clearance of ingested Erwinia carotovora carotovora 15. Nevertheless, flies quickly succumbed to the infection, suggesting a deleterious immune response. In line with this, prolonged overexpression promoted a proinflammatory signature in the gut with induction of JNK and JAK/STAT pathways, increased apoptosis and stem cell proliferation. These findings highlight a novel regulatory mechanism of host-microbe interactions mediated by antagonistic transcription factor isoforms.

  19. Analysis and Application of Antagonism Compound Prescription Compatibility

    Science.gov (United States)

    Li, Mengyan; Wang, Can; Bai, Ming; Miao, Mingsan

    2018-01-01

    Deer horn glue is deer family animals deer or red deer horn made of solid plastic animal medicine, according to Chinese medicine “seven emotions together” theory, the antler and other Chinese herbal medicines compatibility can be better play its Medicinal value. In this paper, the chemical composition, pharmacological effects, compatibility analysis, clinical application and classic ancient prescriptions of antler are reviewed in recent years.

  20. The ribosome-associated complex antagonizes prion formation in yeast.

    Science.gov (United States)

    Amor, Alvaro J; Castanzo, Dominic T; Delany, Sean P; Selechnik, Daniel M; van Ooy, Alex; Cameron, Dale M

    2015-01-01

    The number of known fungal proteins capable of switching between alternative stable conformations is steadily increasing, suggesting that a prion-like mechanism may be broadly utilized as a means to propagate altered cellular states. To gain insight into the mechanisms by which cells regulate prion formation and toxicity we examined the role of the yeast ribosome-associated complex (RAC) in modulating both the formation of the [PSI(+)] prion - an alternative conformer of Sup35 protein - and the toxicity of aggregation-prone polypeptides. The Hsp40 RAC chaperone Zuo1 anchors the RAC to ribosomes and stimulates the ATPase activity of the Hsp70 chaperone Ssb. We found that cells lacking Zuo1 are sensitive to over-expression of some aggregation-prone proteins, including the Sup35 prion domain, suggesting that co-translational protein misfolding increases in Δzuo1 strains. Consistent with this finding, Δzuo1 cells exhibit higher frequencies of spontaneous and induced prion formation. Cells expressing mutant forms of Zuo1 lacking either a C-terminal charged region required for ribosome association, or the J-domain responsible for Ssb ATPase stimulation, exhibit similarly high frequencies of prion formation. Our findings are consistent with a role for the RAC in chaperoning nascent Sup35 to regulate folding of the N-terminal prion domain as it emerges from the ribosome.

  1. What is the clinical significance of ventricular mural antagonism?

    DEFF Research Database (Denmark)

    Lunkenheimer, Paul P; Niederer, Peter; Stephenson, Robert S

    2018-01-01

    alignment, thus deviating from the prevailing tangential orientation. Upon contraction, they produce, in addition to a tangential force, a radial force component that counteracts ventricular constriction and aids widening of the ventricular cavity. In experimental studies, we have provided evidence...... for the existence of such forces, which are auxotonic in nature. This is in contrast to the tangentially aligned myocytes that produce constrictive forces, which are unloading in nature. The ventricular myocardium is, therefore, able to function in an antagonistic fashion, with the prevailing constrictive forces...

  2. genetics, epigenetics and the story of mutual antagonisms

    Indian Academy of Sciences (India)

    Recent years have seen a rapid growth in mouse genetics resources that support research into fundamental mechanisms in organogenesis, including those controlling mammalian sex determinations. Numerous mouse mutants have shed light on molecular pathways of cell fate specification during gonadogenesis and the ...

  3. Antagonism of Roseobacter clade bacteria against pathogenic bacteria

    DEFF Research Database (Denmark)

    Porsby, Cisse Hedegaard

    Ph.d. projektet omhandler brug af probiotiske bakterier mod bakteriesygdomme i fiskeopdræt. Marine bakterier, der tilhører Roseobacter-gruppen, har vist sig at være lovende probiotiske bakterier. En del af bakteriernes probiotiske effekt skyldes sandsynligvis produktion af et antibakerielt stof, ...

  4. [Sugammadex. New pharmacological concept for antagonizing rocuronium and vecuronium

    NARCIS (Netherlands)

    Sparr, H.J.; Booij, L.H.D.J.; Fuchs-Buder, T.

    2009-01-01

    Up to now only acetylcholine esterase inhibitors, such as neostigmine, were available as antagonists of residual neuromuscular blocks. Sugammadex is a modified gamma-cyclodextrin that binds rocuronium and chemically similar aminosteroidal muscle relaxants, such as vecuronium. The underlying

  5. Antagonism between Hedgehog and Wnt signaling pathways regulates tumorigenicity.

    Science.gov (United States)

    Ding, Mei; Wang, Xin

    2017-12-01

    The crosstalk of multiple cellular signaling pathways is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation and metastasis. The Hedgehog (Hh) and Wnt signaling pathways are both considered to be essential regulators of cell proliferation, differentiation and oncogenesis. Recent studies have indicated that the Hh and Wnt signaling pathways are closely associated and involved in regulating embryogenesis and cellular differentiation. Hh signaling acts upstream of the Wnt signaling pathway, and negative regulates Wnt activity via secreted frizzled-related protein 1 (SFRP1), and the Wnt/β-catenin pathway downregulates Hh activity through glioma-associated oncogene homolog 3 transcriptional regulation. This evidence suggests that the imbalance of Hh and Wnt regulation serves a crucial role in cancer-associated processes. The activation of SFRP1, which inhibits Wnt, has been demonstrated to be an important cross-point between the two signaling pathways. The present study reviews the complex interaction between the Hh and Wnt signaling pathways in embryogenesis and tumorigenicity, and the role of SFRP1 as an important mediator associated with the dysregulation of the Hh and Wnt signaling pathways.

  6. Characterization and antagonism of cytokine-induced eosinophil priming

    NARCIS (Netherlands)

    Rosas Rosas, Ana Marcela

    2006-01-01

    Allergic asthma is an inflammatory disease characterized by bronchial hyper-responsiveness, airway inflammation, and reversible obstruction of the airways. In humans, cytokine activated eosinophils are thought to be important players in this process since they can release inflammatory mediators

  7. Explaining Antagonism to the Owners of Foxwoods Casino Resort

    Science.gov (United States)

    d'Hauteserre, Anne-Marie

    2010-01-01

    Conflictual relations between the owners of Foxwoods Casino and Resort, who are American Indians, and the white residents of Ledyard and nearby Preston and North Stonington townships in southeastern Connecticut are long-standing. They have flared up on numerous occasions and especially since 1982 when the Mashantucket Pequots considered building a…

  8. A Highly Arginolytic Streptococcus Species That Potently Antagonizes Streptococcus mutans.

    Science.gov (United States)

    Huang, Xuelian; Palmer, Sara R; Ahn, Sang-Joon; Richards, Vincent P; Williams, Matthew L; Nascimento, Marcelle M; Burne, Robert A

    2016-01-29

    The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus strain, designated strain A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme that were sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to challisin (Sgc) of Streptococcus gordonii that was able to block the competence-stimulating peptide (CSP)-ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative, could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans, but Sgc was not required for this activity. The complete genome sequence of A12 was determined, and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in the promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Differential vascular alpha1-adrenoceptor antagonism by tamsulosin and terazosin

    NARCIS (Netherlands)

    Schäfers, R. F.; Fokuhl, B.; Wasmuth, A.; Schumacher, H.; Taguchi, K.; de Mey, C.; Philipp, T.; Michel, M. C.

    1999-01-01

    AIMS: In patients with lower urinary tract symptoms suggestive of benign prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood pressure whereas only very small if any alterations were reported with the alpha1-adrenoceptor antagonist tamsulosin. Therefore, we have compared

  10. Is there an antagonism between nuclear safety and productivity?

    International Nuclear Information System (INIS)

    Dessus de Cerou, E.; Fourest, B.; Frantzen, C.; Lacoste, A.C.

    1999-01-01

    This article reviews the conference organized by the SFEN on November 10, 1998. The object of this meeting was to overview the recent dispositions taken by EdF about the management of its nuclear power plants. The creation of OSD (safety-availability-observatories) in each nuclear plant, whose purpose is to set a dialogue between the demands of safety and the optimization of production shows the importance given by EdF to provide a safe and competitive energy. It shows also the will of EdF to acknowledge the existence of real conflicts between radiation protection, quality assurance and competitiveness in the daily life of a nuclear facility. EdF will face a partial opening of its market by february 2000 within the limits defined by European regulations. This increase of competition could rise problems between the transparency of nuclear activities, patent rights and information reporting. (A.C.)

  11. Energy mitigation, adaptation and biodiversity: Synergies and antagonisms

    International Nuclear Information System (INIS)

    Berry, P M; Paterson, J S

    2009-01-01

    In this paper we review the current impacts of different energy producers (and energy conservation) on biodiversity and investigate the potential for achieving positive biodiversity effects along with mitigation and adaptation objectives. Very few energy producers achieve all three aims - although it may be possible with careful choice of location and management. In some instances, energy conservation can provide mitigation, adaptation and biodiversity benefits. There is still a gap in knowledge regarding the effects of newer energy technologies on biodiversity. There is an additional concern that many supposedly 'green' renewable energy projects may actually harm biodiversity to such a degree that their overall human benefits are negated. The increasing understanding that ecosystem services are vital for human well-being though means that attempting positive mitigation, adaptation and biodiversity conservation in the energy sector should be an imperative goal for international policy. Whilst research into synergies between mitigation and adaptation is established, there has been very little that has examined the impacts on biodiversity as well. Further work is required to identify and provide evidence of the best ways of optimising mitigation, adaptation and biodiversity in the energy sector.

  12. Antagonism and Imaginaries of Plurality in Bolivian Cinema

    Directory of Open Access Journals (Sweden)

    Valeria Canelas

    2018-03-01

    Full Text Available Nowadays, Bolivian cinema is living a period of great activity in a unstable identitarian landscape, wherein negotiations and conflicts between the different national subjectivities are no longer able to be represented within antagonistic patterns producing uniformity. Firstly, this article deals with Jorge Sanjinés’ Filmography in order to offer an explanatory hypothesis to answer why his last productions seem to have been less engaging for national identitarian dynamics. Secondly, an analysis of a series of short films by the Socavón Cine Collective will take place, so as to underline the most important political gestures displayed by their novel audiovisual rhetoric, which have managed to devise a language capable of a more acute examination of the identitarian plurality present in Bolivia.

  13. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Kroon, Jan; Puhr, M.; Buijs, J.T.; van der Horst, G.; Hemmer, D.M.; Marijt, K.A.; Hwang, M.S.; Masood, M.; Grimm, S.; Storm, Gerrit; Metselaar, Josbert Maarten; Meijer, O.C.; Culig, Z.; van der Pluijm, M.

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  14. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T.; Van Der Horst, Geertje; Lemhemmer, Daniël; Marijt, Koen A.; Hwang, Ming S.; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Meijer, Onno C.; Culig, Zoran; Van Der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCA). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  15. Criticism of technology in a state of antagonism

    International Nuclear Information System (INIS)

    Detzer, K.A.

    1987-01-01

    The book presents a compilation of public lectures, review articles, and statements of opinion from public debates that all refer to topical, socio-political problems in connection with technology and industry, and is intended to reveal structural interdependencies in order to contradict the frequently observed simplifications, prejudices, or ideologies, and in order to point out true arguments that can be used in a fair discussion based on pluralistic principles, about the decisions to be taken. Technology and its impacts on industry, politics, education and ethics. (HSCH) [de

  16. Animosity, antagonism, and avatars: teaching conflict management in second life.

    Science.gov (United States)

    Evans, Dena A; Curtis, Anthony R

    2011-11-01

    Conflict exists in all health care organizations and may take many forms, including lateral or horizontal violence. The Essentials of Baccalaureate Nursing Education identified the development of conflict resolution strategies as core knowledge required of the bachelor's of science in nursing generalist. However, learning the art of conflict management takes both time and practice. With competition for clinical space increasing, class time in short supply, and traditional clinical opportunities for teaching conflict management lacking, a virtual approach to teaching conflict resolution was explored through the use of Second Life®. The project presented here explored students' perceptions of this unique approach to learning conflict management and sought to examine the effectiveness of this teaching method. Copyright 2011, SLACK Incorporated.

  17. Superconductivity and magnetism: From antagonism to mutual interplay

    International Nuclear Information System (INIS)

    Steglich, Frank

    2007-01-01

    In this paper, a brief survey is given on a number of research activities devoted to exploring the relationship between superconductivity and magnetism in f-electron systems. The starting point for these activities has been the pioneering work of 1958 by Matthias and coworkers illustrating the antagonistic nature of the two phenomena. Subsequent efforts concerned the investigation of Kondo superconductors and Kondo-lattice systems (in the 1970s), heavy-fermion metals (in the 1980s and 90s) and quantum critical materials (in the last decade). The latter systems are especially interesting as they promise a deeper insight into the mutual interplay between unconventional superconductivity and magnetism

  18. Antagonizing STAT3 dimerization with a rhodium(III) complex.

    Science.gov (United States)

    Ma, Dik-Lung; Liu, Li-Juan; Leung, Ka-Ho; Chen, Yen-Ting; Zhong, Hai-Jing; Chan, Daniel Shiu-Hin; Wang, Hui-Min David; Leung, Chung-Hang

    2014-08-25

    Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    International Nuclear Information System (INIS)

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  20. Interleukin-1 antagonism in type 1 diabetes of recent onset

    DEFF Research Database (Denmark)

    Moran, Antoinette; Bundy, Brian; Becker, Dorothy J

    2013-01-01

    Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1...... antibody, or anakinra, a human interleukin-1 receptor antagonist, improved β-cell function in recent-onset type 1 diabetes....