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Sample records for spinosad interacts synergistically

  1. Thiamethoxam acts as a target-site synergist of spinosad in resistant strains of Frankliniella occidentalis.

    Science.gov (United States)

    Guillén, Juan; Bielza, Pablo

    2013-02-01

    Previous studies have suggested that the resistance mechanism towards spinosad in Frankliniella occidentalis (Pergande) is an altered target site. Like the neonicotinoids, the spinosyns act on nicotinic acetylcholine receptors (nAChRs) in insects, but at a distinct site. The changes in nAChRs related to spinosad resistance in thrips might involve interaction with neonicotinoids. In this study, the efficacy of spinosad and neonicotinoids, alone and in combination, was evaluated in susceptible and spinosad-resistant thrips strains. The neonicotinoids tested were imidacloprid, thiacloprid, acetamiprid, thiamethoxam and clothianidin. No cross-resistance was shown between spinosad and any of the neonicotinoids. However, an increased toxicity was observed when a mixture of spinosad with thiamethoxam or clothianidin was tested. No synergism was found in the susceptible strains. The more spinosad-resistant the thrips strain, the stronger was the synergism. Data suggest that spinosad and thiamethoxam may interact at the nAChRs in spinosad-resistant thrips, facilitating enhanced insecticidal action. Copyright © 2012 Society of Chemical Industry.

  2. Application of spinosad increases the susceptibility of insecticide-resistant Alphitobius diaperinus (Coleoptera: Tenebrionidae) to pyrethroids.

    Science.gov (United States)

    Lambkin, Trevor A; Furlong, Michael J

    2014-08-01

    The effect of spinosad exposure on the susceptibility of pyrethroid- and organophosphate-resistant populations of lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), to insecticides was investigated in broiler house farm and laboratory studies. A field pyrethroid- and organophosphate-resistant population showed a 3.6-fold increase in susceptibility to gamma-cyhalothrin following spinosad treatment. Overall, cyfluthrin- and fenitrothion-resistant field populations were more susceptible to these insecticides following spinosad treatments, but populations that were not resistant showed no change in susceptibility following spinosad treatment. In a related study, three broiler farm beetle populations with very similar levels of cyfluthrin and gamma-cyhalothrin resistance and similar susceptibilities to spinosad were used to investigate temporal effects of spinosad field treatments on the susceptibility to pyrethroids. Farm insecticide regimes applied at the start of each flock differed: the control broiler house received no insecticide applications, another house was systematically treated with cyfluthrin at the start of each study flock, and the third house was systematically treated with spinosad at the start of five flocks. Afterwards, treatments reverted to cyfluthrin on all farms. At the end of flocks, beetles were tested with cyfluthrin, gamma-cyhalothrin, and spinosad. The control and cyfluthrin house beetles did not change susceptibility to pyrethroids over the period of the study. In the spinosad house, spinosad had no effect on spinosad susceptibility but dramatically increased cyfluthrin and gamma-cyhalothrin susceptibilities. These new susceptibilities were maintained while spinosad applications continued, but pyrethroid susceptibility declined once spinosad applications ceased. This study provides evidence of a synergistic interaction between spinosad and pyrethroids in pyrethroid-resistant beetles. This evidence has significant

  3. Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Ren, Dawei

    structured aggregation consisting of multiple species of bacteria whose function relies on a complex web of cooperative and/or competitive interactions between community members, indicating that research in “whole-entity” should not be based on the assembled results from “mono pieces”. As one of the best...... bacterial species, the study to elucidate the impact of interaction networks on the multispecies biofilms in natural ecosystems, especially in soil, is still at an early stage. The diverse patterns of interactions within the mixed communities as well as the predatorprey relationship between protozoa...... interactions in this four-species biofilm model community. Manuscript 2 presents the further application of this developed approach on evaluating the synergistic/antagonistic interactions in multispecies biofilms composed of seven soil isolates. 63% of the four-species biofilms were found to interact...

  4. Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Ren, Dawei

    that the plasmid host range can be greatly affected by the surrounding bacterial community. This needs to be taken into account as many antibiotic resistance and virulence determinants are plasmid-encoded, which can spread further and raise antibiotic-resistant bacteria in soil....... bacterial species, the study to elucidate the impact of interaction networks on the multispecies biofilms in natural ecosystems, especially in soil, is still at an early stage. The diverse patterns of interactions within the mixed communities as well as the predatorprey relationship between protozoa...... interactions in this four-species biofilm model community. Manuscript 2 presents the further application of this developed approach on evaluating the synergistic/antagonistic interactions in multispecies biofilms composed of seven soil isolates. 63% of the four-species biofilms were found to interact...

  5. Synergistic effects in plasma surface interactions

    International Nuclear Information System (INIS)

    Roberto, J.B.; Behrisch, R.

    1984-01-01

    The possible synergistic effects which can contribute to plasma surface interaction phenomena in fusion devices are reviewed. These effects include the influence of reactive ions, surface modification, temperature, radiation damage, and external forces and fields on erosion yields, hydrogen retention and release, and other surface processes. The important synergistic effects are described in terms of surface and edge conditions encountered in present fusion devices and expected in future reactors. Priority data needs include the chemical erosion of graphite at high particle fluxes, melt-layer stability under disruption-induced eddy current forces, the influence of bulk neutron damage on hydrogen retention, and an in-situ evaluation of synergistic effects in operating fusion devices

  6. Resistance to spinosad in the western flower thrips, Frankliniella occidentalis (Pergande), in greenhouses of south-eastern Spain.

    Science.gov (United States)

    Bielza, Pablo; Quinto, Vicente; Contreras, Josefina; Torné, María; Martín, Alberto; Espinosa, Pedro J

    2007-07-01

    Susceptibility to spinosad of western flower thrips (WFT), Frankliniella occidentalis (Pergande), from south-eastern Spain was determined. LC(50) values of the field populations without previous exposure to spinosad collected in Murcia in 2001 and 2002 ranged from 0.005 to 0.077 mg L(-1). The populations collected in Almeria in 2003 in greenhouses were resistant to spinosad (LC(50) > 54 mg L(-1)) compared with the authors' highly susceptible laboratory strain. The highly sensitive laboratory strain leads to very high resistance ratios for the field populations (>13 500), but these ratios do not necessarily mean resistance problems and control failures (spinosad field rate 90-120 mg L(-1)). The populations collected in Murcia from some greenhouses in 2004 were also resistant to spinosad (RF > 3682). Spinosad overuse, with more than ten applications per crop, produced these resistant populations in some greenhouses. Spinosad showed no cross-resistance to acrinathrin, formetanate or methiocarb in laboratory strains selected for resistance towards each insecticide. Correlation analysis indicated no cross-resistance among spinosad and the other three insecticides in 13 field populations and in nine laboratory strains. The synergists piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and diethyl maleate (DEM) did not enhance the toxicity of spinosad to the resistant strains, indicating that metabolic-mediated detoxification was not responsible for the spinosad resistance. These findings suggest that rotation with spinosad may be an effective resistance management strategy. Copyright (c) 2007 Society of Chemical Industry.

  7. Statistical metamodeling for revealing synergistic antimicrobial interactions.

    Directory of Open Access Journals (Sweden)

    Hsiang Chia Chen

    2010-11-01

    Full Text Available Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future.

  8. Mathematical description of synergistic interaction between radon and smoking

    International Nuclear Information System (INIS)

    Jin Kyu Kim; Petin, V.G.; Belkina, S.V.

    2007-01-01

    Complete text of publication follows. Background: A certain level of background exposure to ionizing radiation and natural or man-made chemicals is always present in the environment. Radon and its short-lived decay products are considered as important sources of public exposure to the natural radioactivity. It is well known from epidemiological and toxicological studies that synergistic interaction between smoking and radon occurs, which is especially important for high natural background areas. Objective: This study has been done to suggest a mathematical model to describe the synergistic interaction of radon with tobacco smoking, and to demonstrate the ability of the model to describe carcinogenic effects of the combined action. Methods: A simple mathematical model was formulated to describe and predict the synergistic interaction of radon with smoking. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arisen from the interaction of sublesions induced by the two factors under consideration. Results: The predictions of the model were verified by comparison with experimental data published by other researchers. The model appears to be appropriate and the predictions are valid. Conclusions: : The suggested mathematical model predicts the greatest level of synergistic effect and condition under which the maximum synergy is attained. The synergistic effect appeared to decline with any deviation from the optimal value of the ratio of carcinogenic effective damages produced by each agent alone.

  9. Pooled screening for synergistic interactions subject to blocking and noise.

    Directory of Open Access Journals (Sweden)

    Kyle Li

    Full Text Available The complex molecular networks in the cell can give rise to surprising interactions: gene deletions that are synthetically lethal, gene overexpressions that promote stemness or differentiation, synergistic drug interactions that heighten potency. Yet, the number of actual interactions is dwarfed by the number of potential interactions, and discovering them remains a major problem. Pooled screening, in which multiple factors are simultaneously tested for possible interactions, has the potential to increase the efficiency of searching for interactions among a large set of factors. However, pooling also carries with it the risk of masking genuine interactions due to antagonistic influence from other factors in the pool. Here, we explore several theoretical models of pooled screening, allowing for synergy and antagonism between factors, noisy measurements, and other forms of uncertainty. We investigate randomized sequential designs, deriving formulae for the expected number of tests that need to be performed to discover a synergistic interaction, and the optimal size of pools to test. We find that even in the presence of significant antagonistic interactions and testing noise, randomized pooled designs can significantly outperform exhaustive testing of all possible combinations. We also find that testing noise does not affect optimal pool size, and that mitigating noise by a selective approach to retesting outperforms naive replication of all tests. Finally, we show that a Bayesian approach can be used to handle uncertainty in problem parameters, such as the extent of synergistic and antagonistic interactions, resulting in schedules for adapting pool size during the course of testing.

  10. Synergistic interaction between two linear inhibitors on a single ...

    African Journals Online (AJOL)

    ). vanadate (Van) and L-phenylalanine (L-phe) were studied using a modification of the common Yonetani-Theorell procedure proposed for studying synergistic inhibition. The modes of inhibition of ALP by Van and L-phe as analysed using the ...

  11. Synergistic interactions promote behavior spreading and alter phase transitions on multiplex networks

    Science.gov (United States)

    Liu, Quan-Hui; Wang, Wei; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng

    2018-02-01

    Synergistic interactions are ubiquitous in the real world. Recent studies have revealed that, for a single-layer network, synergy can enhance spreading and even induce an explosive contagion. There is at the present a growing interest in behavior spreading dynamics on multiplex networks. What is the role of synergistic interactions in behavior spreading in such networked systems? To address this question, we articulate a synergistic behavior spreading model on a double layer network, where the key manifestation of the synergistic interactions is that the adoption of one behavior by a node in one layer enhances its probability of adopting the behavior in the other layer. A general result is that synergistic interactions can greatly enhance the spreading of the behaviors in both layers. A remarkable phenomenon is that the interactions can alter the nature of the phase transition associated with behavior adoption or spreading dynamics. In particular, depending on the transmission rate of one behavior in a network layer, synergistic interactions can lead to a discontinuous (first-order) or a continuous (second-order) transition in the adoption scope of the other behavior with respect to its transmission rate. A surprising two-stage spreading process can arise: due to synergy, nodes having adopted one behavior in one layer adopt the other behavior in the other layer and then prompt the remaining nodes in this layer to quickly adopt the behavior. Analytically, we develop an edge-based compartmental theory and perform a bifurcation analysis to fully understand, in the weak synergistic interaction regime where the dynamical correlation between the network layers is negligible, the role of the interactions in promoting the social behavioral spreading dynamics in the whole system.

  12. DNA damage in human lymphocytes due to synergistic interaction between ionizing radiation and pesticide

    International Nuclear Information System (INIS)

    Kim, J. K.; Lee, K. H.; Lee, B. H.; Chun, K. J.

    2001-01-01

    Biological risks may arise from the possibility of the synergistic interaction between harmful factors such as ionizing radiation and pesticide. The effect of pesticide on radiation-induced DNA damage in human in human blood lymphocytes was evaluated by the single cell gel electrophoresis (SCGE) assay. The lymphocytes, with or without pretreatment of the pesticide, were exposed to 2.0 Gy of gamma ray. Significantly increased tail moment, which was a marker of DNA strand breaks in SCGE assay, showed an excellent dose-response relationship. The present study confirms that the pesticide has the cytotoxic effect on lymphocytes and that it interacts synergistically with ionizing radiationon DNA damage, as well

  13. Overview of QTL detection in plants and tests for synergistic epistatic interactions.

    Science.gov (United States)

    Jannink, Jean-Luc; Moreau, Laurence; Charmet, Gilles; Charcosset, Alain

    2009-06-01

    Improvements in the usefulness of QTL analysis arise from better statistical methods applied to the problem, ability to analyze more complex mating designs, and the fitting of less simplified genetic models. Here we review the advantages of different plant mating designs in QTL analysis and conclude that diallel designs have several favorable properties. We then turn to the detection of systematic genome-wide synergistic epistasis. This form of epistasis has important implications from evolutionary (maintenance of sexual reproduction and concealment of cryptic genetic variation) and practical perspectives (response to pyramided favorable alleles). We develop two methods for detecting systematic synergistic epistasis, one based on analyzing interactions between locus effects and predicted individual genotypic values and one based on analyzing pairwise locus interactions. Using the first method we detect synergistic epistasis in a barley and a wheat dataset but not in a maize dataset. We fail to detect synergistic epistasis with the second method. We discuss our results in the light of theoretical questions concerning the mechanisms of synergistic epistasis.

  14. Mathematical description and prognosis of Synergistic interaction of radon and tobacco smoking

    International Nuclear Information System (INIS)

    Kim, J. K.; Belkina, S. A.; Petin, V. G.

    2007-01-01

    : Radon and its short-lived decay products are considered as the important sources of public exposure to natural radioactivity. The synergistic interaction between tobacco smoking and radon is known to be an actual problem. This study has provided a mathematical description and prognosis of the carcinogenic effects after combined action of radon with smoking. Materials and Methods: A simple mathematical model was adjusted for the optimization and prognosis of the synergistic interaction of radon with smoking. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arising from the interaction of sub lesions induced by the two agents under consideration. Results: The predictions of the model were verified by comparison with experimental data published by other researchers. The model appears to be appropriate and the predictions valid. Conclusion: The suggested mathematical model predicts the greatest level of synergistic effect and condition under which this level is reached. The synergistic effect appeared to decline with any deviation from the optimal value of the ratio of carcinogenic effective damages produced by each agent alone

  15. Investigation of antioxidant interactions between Radix Astragali and Cimicifuga foetida and identification of synergistic antioxidant compounds.

    Directory of Open Access Journals (Sweden)

    Fei Wang

    Full Text Available The medicinal plants of Huang-qi (Radix Astragali and Sheng-ma (Cimicifuga foetida demonstrate significantly better antioxidant effects when used in combination than when used alone. However, the bioactive components and interactional mechanism underlying this synergistic action are still not well understood. In the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging assay was employed to investigate the antioxidant capacity of single herbs and their combination with the purpose of screening synergistic antioxidant compounds from them. Chromatographic isolation was performed on silica gel, Sephadex LH-20 columns and HPLC, and consequently to yield formononetin, calycosin, ferulic acid and isoferulic acid, which were identified by their retention time, UV λmax, MS and MS/MS data. The combination of isoferulic acid and calycosin at a dose ratio of 1∶1 resulted in significant synergy in scavenging DPPH radicals and ferric reducing antioxidant power (FRAP assay. Furthermore, the protective effects of these four potential synergistic compounds were examined using H2O2-induced HepG2 Cells bioassay. Results revealed that the similar synergy was observed in the combination of isoferulic acid and calycosin. These findings might provide some theoretical basis for the purported synergistic efficiency of Huang-qi and Sheng-ma as functional foods, dietary supplements and medicinal drugs.

  16. Investigation of antioxidant interactions between Radix Astragali and Cimicifuga foetida and identification of synergistic antioxidant compounds.

    Science.gov (United States)

    Wang, Fei; Zhao, Shancang; Li, Feng; Zhang, Bo; Qu, Yi; Sun, Tianlei; Luo, Ting; Li, Dapeng

    2014-01-01

    The medicinal plants of Huang-qi (Radix Astragali) and Sheng-ma (Cimicifuga foetida) demonstrate significantly better antioxidant effects when used in combination than when used alone. However, the bioactive components and interactional mechanism underlying this synergistic action are still not well understood. In the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was employed to investigate the antioxidant capacity of single herbs and their combination with the purpose of screening synergistic antioxidant compounds from them. Chromatographic isolation was performed on silica gel, Sephadex LH-20 columns and HPLC, and consequently to yield formononetin, calycosin, ferulic acid and isoferulic acid, which were identified by their retention time, UV λmax, MS and MS/MS data. The combination of isoferulic acid and calycosin at a dose ratio of 1∶1 resulted in significant synergy in scavenging DPPH radicals and ferric reducing antioxidant power (FRAP) assay. Furthermore, the protective effects of these four potential synergistic compounds were examined using H2O2-induced HepG2 Cells bioassay. Results revealed that the similar synergy was observed in the combination of isoferulic acid and calycosin. These findings might provide some theoretical basis for the purported synergistic efficiency of Huang-qi and Sheng-ma as functional foods, dietary supplements and medicinal drugs.

  17. [Mathematical modeling of synergistic interaction of sequential thermoradiation action on mammalian cells].

    Science.gov (United States)

    Belkina, S V; Semkina, M A; Kritskiĭ, R O; Petin, V G

    2010-01-01

    Data obtained by other authors for mammalian cells treated by sequential action of ionizing radiation and hyperthermia were used to estimate the dependence of synergistic enhancement ratio on the ratio of damages induced by these agents. Experimental results were described and interpreted by means of the mathematical model of synergism in accordance with which the synergism is expected to result from the additional lethal damage arising from the interaction of sublesions induced by both agents.

  18. Sex-specific spinosad resistance in Danish houseflies

    DEFF Research Database (Denmark)

    Højland, Dorte Heidi

    Spinosad is a novel insecticide which is useful for control of multiple insect pests and it was introduced for housefly control within the last decade. Prior to the introduction of spinosad in Denmark, a survey of Danish houseflies from farms all over the country was initiated, and we discovered...... a strain that was resistant to spinosad. However, this cross-resistance was unusual because females were 26-fold resistant, while males were only 6-fold resistant. This pattern of resistance does not match any known resistance to other insecticides and is different from spinosad resistance in other...... countries. Discovering the reasons behind this sex specific resistance will shed some light in mechanisms behind spinosad resistance in the housefly....

  19. Synergistic interactions of ecosystem services: florivorous pest control boosts crop yield increase through insect pollination

    Science.gov (United States)

    Albrecht, Matthias

    2016-01-01

    Insect pollination and pest control are pivotal functions sustaining global food production. However, they have mostly been studied in isolation and how they interactively shape crop yield remains largely unexplored. Using controlled field experiments, we found strong synergistic effects of insect pollination and simulated pest control on yield quantity and quality. Their joint effect increased yield by 23%, with synergistic effects contributing 10%, while their single contributions were 7% and 6%, respectively. The potential economic benefit for a farmer from the synergistic effects (12%) was 1.8 times greater than their individual contributions (7% each). We show that the principal underlying mechanism was a pronounced pest-induced reduction in flower lifetime, resulting in a strong reduction in the number of pollinator visits a flower receives during its lifetime. Our findings highlight the importance of non-additive interactions among ecosystem services (ES) when valuating, mapping or predicting them and reveal fundamental implications for ecosystem management and policy aimed at maximizing ES for sustainable agriculture. PMID:26865304

  20. Synergistic effect of temperature, protein and salt concentration on structures and interactions among lysozyme proteins

    Science.gov (United States)

    Kundu, Sarathi; Aswal, V. K.; Kohlbrecher, Joachim

    2016-07-01

    Synergistic effect of temperature, protein and salt concentration on structures and interactions among lysozyme proteins in solution has been studied using small angle neutron scattering technique. Scattering study shows that for a particular protein concentration, with increasing temperature, short-range attraction decreases but long-range repulsion becomes system specific. In absence of salt, lower value of attractive interaction is obtained, however, in presence of salt it becomes higher and decreases with increasing temperature. For specific condition, weak long range attraction and intermediate range repulsion exists. At higher temperature (90 °C), fractal structure develops and the corresponding fractal dimension depends upon the experimental conditions.

  1. Geminivirus mixed infection on pepper plants: Synergistic interaction between PHYVV and PepGMV

    Directory of Open Access Journals (Sweden)

    Rivera-Bustamante Rafael F

    2011-03-01

    Full Text Available Abstract Background PHYVV and PepGMV are plant viruses reported in Mexico and Southern US as causal agents of an important pepper disease known as "rizado amarillo". Mixed infections with PHYVV and PepGMV have been reported in several hosts over a wide geographic area. Previous work suggested that these viruses might interact at the replication and/or movement level in a complex manner. The aim of present report was to study some aspects of a synergistic interaction between PHYVV and PepGMV in pepper plants. These include analyses of symptom severity, viral DNA concentration and tissue localization of both viruses in single and mixed infections. Results Mixed infections with PepGMV and PHYVV induced symptoms more severe than those observed in single viral infections. Whereas plants infected with either virus (single infection presented a remission stage with a corresponding decrease in viral DNA levels, double-infected plants did not present symptom remission and both viral DNA concentrations dramatically increased. In situ hybridization experiments revealed that both viruses are restricted to the vascular tissue. Interestingly, the amount of viral DNA detected was higher in plants inoculated with PepGMV than that observed in PHYVV-infected plants. During mixed infections, the location of both viruses remained similar to the one observed in single infections, although the number of infected cells increases. Infections with the tripartite mixture PHYVV (A+B + PepGMV A produced a similar synergistic infection to the one observed after inoculation with both full viruses. On the contrary, tripartite mixture PepGMV (A+B + PHYVV A did not produce a synergistic interaction. In an attempt to study the contribution of individual genes to the synergism, several mutants of PHYVV or PepGMV were inoculated in combination with the corresponding wild type, second virus (wt PepGMV or wt PHYVV. All combinations tested resulted in synergistic infections, with

  2. Synergistic interaction of Smac mimetic and IFNα to trigger apoptosis in acute myeloid leukemia cells.

    Science.gov (United States)

    Bake, Vanessa; Roesler, Stefanie; Eckhardt, Ines; Belz, Katharina; Fulda, Simone

    2014-12-28

    Therapeutic targeting of inhibitor of apoptosis (IAP) proteins by small-molecule inhibitors such as Smac mimetic is considered as a promising anticancer strategy to elicit apoptosis. Recent advances have renewed the interest in exploiting the antileukemic activity of interferon (IFN)α for the treatment of acute myeloid leukemia (AML). Here, we identify a novel synergistic interaction of the Smac mimetic BV6 and IFNα to trigger cell death in AML cells. Calculation of combination index (CI) confirms the synergism of BV6 and IFNα. In contrast to AML cells, no synergistic toxicity of BV6 and IFNα at equimolar concentrations is found against normal peripheral blood lymphocytes. BV6 and IFNα act in concert to stimulate expression of tumor necrosis factor (TNF)α and its secretion into the supernatant, thereby initiating an autocrine/paracrine TNFα/TNF receptor 1 (TNFR1) loop that drives cell death by BV6 and IFNα. Consistently, pharmacological inhibition of TNFα by the TNFα-blocking antibody Enbrel or genetic silencing of TNFR1 significantly reduces BV6/IFNα-induced cell death. In addition, BV6/IFNα-induced cell death depends on interferon regulatory factor (IRF)1, since RNA interference-imposed knockdown of IRF1 significantly rescues cell death. In conclusion, the identification of a novel synergistic antileukemic combination of Smac mimetic and IFNα has important implications for the development of innovative treatment strategies in AML. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Robot- and computer-assisted craniotomy (CRANIO): from active systems to synergistic man-machine interaction.

    Science.gov (United States)

    Cunha-Cruz, V; Follmann, A; Popovic, A; Bast, P; Wu, T; Heger, S; Engelhardt, M; Schmieder, K; Radermacher, K

    2010-01-01

    Computer and robot assistance in craniotomy/craniectomy procedures is intended to increase precision and efficiency of the removal of calvarial tumours, enabling the preoperative design and manufacturing of the corresponding implant. In the framework of the CRANIO project, an active robotic system was developed to automate the milling processes based on a predefined resection planning. This approach allows for a very efficient milling process, but lacks feedback of the intra-operative process to the surgeon. To better integrate the surgeon into the process, a new teleoperated synergistic architecture was designed. This enables the surgeon to realize changes during the procedure and use their human cognitive capabilities. The preoperative planning information is used as guidance for the user interacting with the system through a master-slave architecture. In this article, the CRANIO system is presented together with this new synergistic approach. Experiments have been performed to evaluate the accuracy of the system in active and synergistic modes for the bone milling procedure. The laboratory studies showed the general feasibility of the new concept for the selected medical procedure and determined the accuracy of the system. Although the integration of the surgeon partially reduces the efficiency of the milling process compared with a purely active (automatic) milling, it provides more feedback and flexibility to the user during the intra-operative procedure.

  4. Response surface analysis of synergistic interactions of morphine and gabapentin in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    on the AIC criterion. Result The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58...... % for the synergistic doses. Conclusions The finding of dose-dependent synergistic interactions might indicate that there is a high potential for gabapentin and morphine to be used in combination in the clinic, in order to optimize postoperative pain management and minimize side effects of morphine. 1. Brennan TJ......, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain [Internet]. 1996 Mar;64(3):493–501. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8783314 2. Greco W, Bravo G, Parsons J. The search for synergy: A critical review from a responce surface perspective. Pharmacol Rev...

  5. Proteasome inhibitor carfilzomib interacts synergistically with histone deacetylase inhibitor vorinostat in Jurkat T-leukemia cells.

    Science.gov (United States)

    Gao, Minjie; Gao, Lu; Tao, Yi; Hou, Jun; Yang, Guang; Wu, Xiaosong; Xu, Hongwei; Tompkins, Van S; Han, Ying; Wu, Huiqun; Zhan, Fenghuang; Shi, Jumei

    2014-06-01

    In the present study, we investigated the interactions between proteasome inhibitor carfilzomib (CFZ) and histone deacetylase inhibitor vorinostat in Jurkat T-leukemia cells. Coexposure of cells to minimally lethal concentrations of CFZ with very low concentration of vorinostat resulted in synergistic antiproliferative effects and enhanced apoptosis in Jurkat T-leukemia cells, accompanied with the sharply increased reactive oxygen species (ROS), the striking decrease in the mitochondrial membrane potential (MMP), the increased release of cytochrome c, the enhanced activation of caspase-9 and -3, and the cleavage of PARP. The combined treatment of Jurkat cells pre-treated with ROS scavengers N-acetylcysteine (NAC) significantly blocked the loss of mitochondrial membrane potential, suggesting that ROS generation was a former event of the loss of mitochondrial membrane potential. Furthermore, NAC also resulted in a marked reduction in apoptotic cells, indicating a critical role for increased ROS generation by combined treatment. In addition, combined treatment arrested the cell cycle in G2-M phase. These results imply that CFZ interacted synergistically with vorinostat in Jurkat T-leukemia cells, which raised the possibility that the combination of carfilzomib with vorinostat may represent a novel strategy in treating T-cell Leukemia. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  6. Synergistic interactions of biotic and abiotic environmental stressors on gene expression.

    Science.gov (United States)

    Altshuler, Ianina; McLeod, Anne M; Colbourne, John K; Yan, Norman D; Cristescu, Melania E

    2015-03-01

    Understanding the response of organisms to multiple stressors is critical for predicting if populations can adapt to rapid environmental change. Natural and anthropogenic stressors often interact, complicating general predictions. In this study, we examined the interactive and cumulative effects of two common environmental stressors, lowered calcium concentration, an anthropogenic stressor, and predator presence, a natural stressor, on the water flea Daphnia pulex. We analyzed expression changes of five genes involved in calcium homeostasis - cuticle proteins (Cutie, Icp2), calbindin (Calb), and calcium pump and channel (Serca and Ip3R) - using real-time quantitative PCR (RT-qPCR) in a full factorial experiment. We observed strong synergistic interactions between low calcium concentration and predator presence. While the Ip3R gene was not affected by the stressors, the other four genes were affected in their transcriptional levels by the combination of the stressors. Transcriptional patterns of genes that code for cuticle proteins (Cutie and Icp2) and a sarcoplasmic calcium pump (Serca) only responded to the combination of stressors, changing their relative expression levels in a synergistic response, while a calcium-binding protein (Calb) responded to low calcium stress and the combination of both stressors. The expression pattern of these genes (Cutie, Icp2, and Serca) were nonlinear, yet they were dose dependent across the calcium gradient. Multiple stressors can have complex, often unexpected effects on ecosystems. This study demonstrates that the dominant interaction for the set of tested genes appears to be synergism. We argue that gene expression patterns can be used to understand and predict the type of interaction expected when organisms are exposed simultaneously to natural and anthropogenic stressors.

  7. Spinosad resistance, esterase isoenzymes and temporal synergism in Frankliniella occidentalis (Pergande) in Australia.

    Science.gov (United States)

    Herron, Grant A; Gunning, Robin V; Cottage, Emma L A; Borzatta, Valerio; Gobbi, Carlotta

    2014-09-01

    Spinosad has been widely used in Australia to control western flower thrips Frankliniella occidentalis (Pergande) but spinosad usefulness is now compromised by resistance. Here we studied a highly spinosad resistant strain of F. occidentalis to explore if esterases had a role in spinosad resistance. Enhanced esterase activity in pressured spinosad-resistant F. occidentalis was confirmed via PAGE electrophoresis and estimated to be approximately three times higher than that in a susceptible strain. Spinosad-esterase inhibition data in the resistant strain, showed a concentration effect with significant esterase-spinosad binding occurring at spinosad concentrations from 6.2× 10(-7) to 1.5× 10(-5) M. Similarly, a spinosad-piperonyl butoxide (PBO) inhibition curve showed a concentration effect, with significant esterase-PBO binding occurring in the resistant strain at PBO concentrations between 3.3× 10(-5) M and 8.4× 10(-4) M. No binding of esterase to spinosad or PBO occurred in the susceptible strain. Results of bioassays in which spinosad resistant F. occidentalis were sprayed with a 4h delayed release formulation of cyclodextrin-complexed spinosad with immediately available PBO demonstrated that spinosad resistance was significantly reduced from 577 to 72-fold. With further development the PBO synergism of spinosad using a delayed release formulation, similar to that used here, may provide effective control for spinosad resistant F. occidentalis. Temporal synergism of spinosad may prove to be effective tactic for the control of spinosad resistant F. occidentalis where the main resistance mechanism involved has been confirmed to be esterase based. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

    Science.gov (United States)

    Moon, Shinje; Yoo, Hyung-Joon; Ahn, You-Hern; Kim, Gheun-Ho; Yu, Jae Myung; Park, Joon-Sung

    2018-01-01

    The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.07; HbA1c, OR = 1.16, 95% CI = 1.04-1.30; diabetic duration, OR = 1.06, 95% CI = 1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ≥10 years (adjusted RERI = 0.92, 95% CI = 0.10-1.74; adjusted AP = 0.29, 95% CI = -0.82-1.41; adjusted S = 1.76, 95% CI = 1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  9. Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions

    Science.gov (United States)

    Biswas, Rajib; Bagchi, Biman

    2018-01-01

    In nature, water is often found in contact with surfaces that are extended on the scale of molecule size but small on a macroscopic scale. Examples include lipid bilayers and reverse micelles as well as biomolecules like proteins, DNA and zeolites, to name a few. While the presence of surfaces and interfaces interrupts the continuous hydrogen bond network of liquid water, confinement on a mesoscopic scale introduces new features. Even when extended on a molecular scale, natural and biological surfaces often have features (like charge, hydrophobicity) that vary on the scale of the molecular diameter of water. As a result, many new and exotic features, which are not seen in the bulk, appear in the dynamics of water close to the surface. These different behaviors bear the signature of both water–surface interactions and of confinement. In other words, the altered properties are the result of the synergistic effects of surface–water interactions and confinement. Ultrafast spectroscopy, theoretical modeling and computer simulations together form powerful synergistic approaches towards an understanding of the properties of confined water in such systems as nanocavities, reverse micelles (RMs), water inside and outside biomolecules like proteins and DNA, and also between two hydrophobic walls. We shall review the experimental results and place them in the context of theory and simulations. For water confined within RMs, we discuss the possible interference effects propagating from opposite surfaces. Similar interference is found to give rise to an effective attractive force between two hydrophobic surfaces immersed and kept fixed at a separation of d, with the force showing an exponential dependence on this distance. For protein and DNA hydration, we shall examine a multitude of timescales that arise from frustration effects due to the inherent heterogeneity of these surfaces. We pay particular attention to the role of orientational correlations and modification of

  10. Theory of synergistic effects: Hill-type response surfaces as 'null-interaction' models for mixtures.

    Science.gov (United States)

    Schindler, Michael

    2017-08-02

    The classification of effects caused by mixtures of agents as synergistic, antagonistic or additive depends critically on the reference model of 'null interaction'. Two main approaches are currently in use, the Additive Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM) or independent action (IA) models. We compare several response surface models to a newly developed Hill response surface, obtained by solving a logistic partial differential equation (PDE). Assuming that a mixture of chemicals with individual Hill-type dose-response curves can be described by an n-dimensional logistic function, Hill's differential equation for pure agents is replaced by a PDE for mixtures whose solution provides Hill surfaces as 'null-interaction' models and relies neither on Bliss independence or Loewe additivity nor uses Chou's unified general theory. An n-dimensional logistic PDE decribing the Hill-type response of n-component mixtures is solved. Appropriate boundary conditions ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica Version 11.0, 2016) is used for the mathematics and graphics presented in this article. The Hill response surface ansatz can be applied to mixtures of compounds with arbitrary Hill parameters. Restrictions which are required when deriving analytical expressions for response surfaces from other principles, are unnecessary. Many approaches based on Loewe additivity turn out be special cases of the Hill approach whose increased flexibility permits a better description of 'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's model in agrochemistry, leads to incompatibility with the Hill surface ansatz. Examples of binary and ternary mixtures illustrate the differences between the approaches. For Hill-slopes close to one and doses below the half-maximum effect doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the Hill model indicates 'null-interaction

  11. Structural Change of Biomolecules and Application of Synergistic Interaction by Radiation

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Kim, J. H.; Yang, J. S.

    2008-12-01

    It is expected that motivation and basic technologies for the future R and D plans can be provided from the results of this study. This study has been done to develop fundamentals for radiation applications based on the existing radiation technology, and to establish technical basis for enhancing efficacy of radiation utilization by studying the simultaneous application of ionizing radiation with another factor. Application of radiation technology together with the existing technologies to enhance the physical, chemical, biological characteristics through structural changes of biomolecules will exert a favorable influence on the creation of de novo scientific and industrial values. A theoretical model for the combined action of ionizing radiation with another factor can make it possible to predict a prior the maximum value of synergistic interaction and the conditions for it. Furthermore, the results of this study give a clues for establishment of fundamental theories associated with positive efficacy of radiation applications

  12. Synergistic interactions with a high intraoperative expander fill volume increase the risk for mastectomy flap necrosis.

    Science.gov (United States)

    Khavanin, Nima; Jordan, Sumanas; Lovecchio, Francis; Fine, Neil A; Kim, John

    2013-12-01

    Prosthetic-based breast reconstruction is performed with increasing frequency in the United States. Major mastectomy skin flap necrosis is a significant complication with outcomes ranging from poor aesthetic appearance to reconstructive failure. The present study aimed to explore the interactions between intraoperative fill and other risk factors on the incidence of flap necrosis in patients undergoing mastectomy with immediate expander/implant-based reconstruction. A retrospective review of 966 consecutive patients (1,409 breasts) who underwent skin or nipple sparing mastectomy with immediate tissue expander reconstruction at a single institution was conducted. Age, body mass index, hypertension, smoking status, premastectomy and postmastectomy radiation, acellular dermal matrix use, and application of the tumescent mastectomy technique were analyzed as potential predictors of flap necrosis both independently and as synergistic variables with high intraoperative fill. The following three measures of interaction were calculated: relative excess risk due to interaction, attributable proportion of risk due to interaction, and synergy index (SI). Intraoperative tissue expander fill volume was high (≥66.7% of the maximum volume) in 40.9% (576 of 1,409 breasts) of cases. The unadjusted flap necrosis rate was greater in the high intraoperative fill cohort than in the low fill cohort (10.4% vs. 7.1%, p=0.027). Multivariate logistic regression did not identify high intraoperative fill volume as an independent risk factor for flap necrosis (odds ratio 1.442, 95% confidence interval 0.973-2.137, p=0.068). However, four risk factors were identified that interacted significantly with intraoperative fill volume, namely tumescence, age, hypertension, and obesity. The SI, or the departure from additive risks, was largest for tumescence (SI, 25.3), followed by hypertension (SI, 2.39), obesity (SI, 2.28), and age older than 50 years (SI, 1.17). In the postmastectomy, hypovascular

  13. Characterization of the interaction between cadmium and chlorpyrifos with integrative techniques in incurring synergistic hepatoxicity.

    Directory of Open Access Journals (Sweden)

    Liqun Chen

    Full Text Available Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd and chlorpyrifos (CPF in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and (1H NMR to study the interaction between Cd(2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd(2+ and CPF, which might be the bonding between Cd(2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd(2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress.

  14. Synergistic interaction between job control and social support at work on depression, burnout, and insomnia among Japanese civil servants.

    Science.gov (United States)

    Saijo, Yasuaki; Chiba, Shigeru; Yoshioka, Eiji; Nakagi, Yoshihiko; Ito, Toshihiro; Kitaoka-Higashiguchi, Kazuyo; Yoshida, Takahiko

    2015-02-01

    To elucidate whether low job control and low social support at work have synergistic interaction on mental health. The synergistic interaction was also analyzed after stratification by high and low job demands. Participants were 2,121 local government employees in Asahikawa city, Japan. The Brief Job Stress Questionnaire was used to assess job demands, job control, and social support. Depression was assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory-General Survey was used to assess burnout. Insomnia was assessed using the Athens Insomnia Scale. Possible confounder-adjusted logistic regression analyses were performed to obtain odds ratios for depression, burnout, and insomnia, and synergy indices between job control and social support at work were assessed. The synergy indices among men and women, respectively, were 2.08 (80 % confidence interval: 1.01, 4.27) and 1.98 (0.67, 5.89) for depression, 1.79 (1.28, 2.51) and 2.62 (1.07, 6.40) for burnout, and 1.92 (1.22, 3.02) and 2.77 (0.43, 18.01) for insomnia. Men with high job demands had higher synergistic interaction on depression and burnout, compared to men with low job demands, and women with low job demands had higher synergistic interaction between job control and social support at work on burnout and insomnia, compared to women with high job demands. There were more-than-additive interactions of job control and social support at work on depression, burnout, and insomnia. After stratification by job demands, the synergistic interaction may be different between men and women. To assess job stress, it is necessary to consider the interactive effect of not only job demands and job control but also job control and social support at work.

  15. Effect of xanthan and locust bean gum synergistic interaction on characteristics of biodegradable edible film.

    Science.gov (United States)

    Kurt, Abdullah; Toker, Omer Said; Tornuk, Fatih

    2017-09-01

    The present study was aimed to use different combinations of xanthan (XG) and locust bean gum (LBG) in the biodegradable edible film preparation by benefitting from their synergistic interactions for the first time. Concentrations of LBG, XG and glycerol of the optimized film sample were found to be 89.6%, 10.4% and 20%, respectively. At the optimum point the WVP, TS, E% and EM values of film were found 0.22gmmh -1 m 2 kPa, 86.97MPa, 33.34% and 177.25MPa, respectively. The optimized film was characterized for its physical, thermal and structural behavior. The scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) analyses exhibited miscibility and presence of interaction between polymers. In conclusion, XG and LBG interaction was used successfully to get biodegradable films and coatings with improved characteristics. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Synergistic Interactions of a Synthetic Lubricin-Mimetic with Fibronectin for Enhanced Wear Protection

    Directory of Open Access Journals (Sweden)

    Roberto C. Andresen Eguiluz

    2017-06-01

    Full Text Available Lubricin (LUB, a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN, a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA normal force measurements indicate that the lubricin-mimetic (mimLUB could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also extend the wearless friction regime of the polymer up to pressures of 3.4 MPa while ensuring stable friction coefficients (μ ≈ 0.28. These results demonstrate synergistic interactions between mimLUB and FN in assisting the lubrication and wear protection of ideal (mica substrates upon shear. Collectively, these findings suggest that our proposed mimLUB might be a promising alternative to LUB, as similar mechanisms could potentially facilitate the interaction between the polymer and cartilage surfaces in articular joints and prosthetic implants in vivo.

  17. Home Remodeling and Food Allergy Interact Synergistically to Increase the Risk of Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Won Seok Lee

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the effects of home remodeling and food allergy (FA on the development of atopic dermatitis (AD in children. Methods. The Modified International Study of Asthma and Allergies in Childhood questionnaire was used to survey 4,111 children recruited from 3 kindergartens and 6 elementary schools from Seongnam, Korea. Participants’ parents agreed for them to participate in physical examinations, skin prick tests, and blood tests. Results. Home remodeling in the past 12 months (adjusted odds ratio [aOR] 3.40, P=0.006, lifetime diagnosis of FA (aOR 3.95, P<0.001, parental history of AD (aOR 2.67, P=0.001, and FA (aOR 2.35, P=0.004 were independent risk factors for lifetime diagnosis of AD ever. When history of home remodeling and FA were combined, the risk for moderate-to-severe AD by scoring atopic dermatitis (SCORAD score increased (aOR, 7.19, P=0.011, P for interaction = 0.034. Conclusion. Home remodeling, lifetime diagnosis of FA, parental history of AD, and parental history of FA were independent risk factors for AD. In addition, we observed a synergistic interaction between home remodeling and FA in the risk of moderate-to-severe AD.

  18. Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

    Science.gov (United States)

    De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

    2014-10-15

    The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Synergistic Interactions within a Multispecies Biofilm Enhance Individual Species Protection against Grazing by a Pelagic Protozoan

    Directory of Open Access Journals (Sweden)

    Prem K. Raghupathi

    2018-01-01

    Full Text Available Biofilm formation has been shown to confer protection against grazing, but little information is available on the effect of grazing on biofilm formation and protection in multispecies consortia. With most biofilms in nature being composed of multiple bacterial species, the interactions and dynamics of a multispecies bacterial biofilm subject to grazing by a pelagic protozoan predator were investigated. To this end, a mono and multispecies biofilms of four bacterial soil isolates, namely Xanthomonas retroflexus, Stenotrophomonas rhizophila, Microbacterium oxydans and Paenibacillus amylolyticus, were constructed and subjected to grazing by the ciliate Tetrahymena pyriformis. In monocultures, grazing strongly reduced planktonic cell numbers in P. amylolyticus and S. rhizophila and also X. retroflexus. At the same time, cell numbers in the underlying biofilms increased in S. rhizophila and X. retroflexus, but not in P. amylolyticus. This may be due to the fact that while grazing enhanced biofilm formation in the former two species, no biofilm was formed by P. amylolyticus in monoculture, either with or without grazing. In four-species biofilms, biofilm formation was higher than in the best monoculture, a strong biodiversity effect that was even more pronounced in the presence of grazing. While cell numbers of X. retroflexus, S. rhizophila, and P. amylolyticus in the planktonic fraction were greatly reduced in the presence of grazers, cell numbers of all three species strongly increased in the biofilm. Our results show that synergistic interactions between the four-species were important to induce biofilm formation, and suggest that bacterial members that produce more biofilm when exposed to the grazer not only protect themselves but also supported other members which are sensitive to grazing, thereby providing a “shared grazing protection” within the four-species biofilm model. Hence, complex interactions shape the dynamics of the biofilm and

  20. Critical nutrient thresholds needed to control eutrophication and synergistic interactions between phosphorus and different nitrogen sources.

    Science.gov (United States)

    Zeng, Qinghui; Qin, Lihuan; Bao, Linlin; Li, Yayong; Li, Xuyong

    2016-10-01

    Eutrophication is one of the greatest threats to global freshwater ecosystems. The phytoplankton responses to nutrient inputs vary in different water bodies, so it is particularly important to determine the nutrient thresholds and synergistic interactions between nutrients in different freshwater ecosystems. Field sampling and bioassay experiments were conducted to determine the thresholds of soluble reactive phosphorus (SRP), nitrate-nitrogen (NO 3 -N), and ammonium-nitrogen (NH 4 -N) in Miyun Reservoir. A separate nutrient addition bioassay was designed to assess the synergistic interactions between these nutrients. Chlorophyll a (Chl a) concentrations were used to estimate phytoplankton biomass. The results showed the following: (1) nutrient threshold bioassay indicated that eutrophication thresholds of SRP, NO 3 -N, and NH 4 -N should be targeted at below 0.04 mg P L -1 , 0.5 mg N L -1 , and 0.3 mg N L -1 , respectively, to limit the growth of phytoplankton. (2) The stimulatory effect of "NH 4 -N plus P" on phytoplankton biomass was greater than "NO 3 -N plus P" at the same N concentration, and "NH 4 -N plus NO 3 -N" did not show such associated stimulatory effect as "NH 4 -N plus P" or "NO 3 -N plus P". (3) The average concentrations of total phosphorus (TP), NO 3 -N, and NH 4 -N in Miyun Reservior were 0.017 mg P L -1 , 0.620 mg N L -1 , and 0.143 mg N L -1 , respectively. The reservoir-wide average Chl a is below 20 μg L -1 on an annual basis. (4) Ammonium was an important factor for the growth of phytoplankton and inputs of both NH 4 -N and NO 3 -N should be reduced to control bloom formation. Our findings imply that although P load reduction is important, appropriate reductions of all forms of N in watershed is recommended in the nutrient management strategy for Miyun Reservoir.

  1. Citral, a monoterpenoid aldehyde interacts synergistically with norfloxacin against methicillin resistant Staphylococcus aureus.

    Science.gov (United States)

    Gupta, Priyanka; Patel, Dinesh Kumar; Gupta, Vivek Kumar; Pal, Anirban; Tandon, Sudeep; Darokar, M P

    2017-10-15

    Staphylococcus aureus (SA), is a major human pathogen causing wide range of clinical infections, which has been further complicated by drug resistance like methicillin resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA)/vancomycin resistant S. aureus (VRSA), etc. The present study was aimed at determining anti-staphylococcal potential of citral against drug resistant clinical isolates alone and in combination with antibiotics. To assess the potential of citral in combination with norfloxacin in treating drug resistant infections of SA. In the present study, synergistic interaction of citral and norfloxacin against drug resistant SA strains was evaluated. Further the efficacy and possible mechanism of action of the combination was also evaluated using in vitro and in vivo assays. The anti-staphylococcal activity of each of the monoterpene and the antibiotic was determined in terms of MIC and the effective concentration of both compounds in combination was obtained by checkerboard assay. In vivo efficacy and oral acute toxicity was evaluated in Swiss albino mice model. To understand the mechanism of action, time-kill curve, bacteriolysis, leakage, membrane depolarization, salt tolerance and ethidium bromide efflux assays were performed. Citral was found effective against clinical isolates of SA with MIC values ranging from 75 to 150 µg ml -1 exhibiting bacteriostatic activity. Citral interacted synergistically, reducing MIC of norfloxacin up to 32-folds with FICI ≤ 0.50. Citral did not affect cell wall, but could damage cell membrane, inhibit efflux pump and affect the membrane potential. Citral could reduce the staphylococcal load of spleen and liver tissues in a dose-dependent manner which was further reduced when used in combination with norfloxacin. Citral did not exhibit any mortality or morbidity up to 500 mg kg -1 body weight and found to prolong the post-antibiotic effect of norfloxacin. Based on these observations, citral could be

  2. Synergistic interactions of bradykinin, thrombin, interleukin 1 and tumor necrosis factor on prostanoid biosynthesis in human periodontal-ligament cells.

    Science.gov (United States)

    Ransjö, M; Marklund, M; Persson, M; Lerner, U H

    1998-04-01

    Prostaglandins are involved in force-induced orthodontic tooth movement. Bradykinin (BK) and thrombin are known to cause a significant time- and concentration-dependent burst of prostanoid biosynthesis in cultured human periodontal-ligament (PDL) cells. The aim now was to investigate interactive effects between interleukin 1 alpha, -beta (IL-1 alpha, -1 beta), tumour necrosis factor-alpha,-beta (TNF-alpha, -beta) and BK or thrombin on prostaglandin biosynthesis in human PDL cells. IL-1 alpha and -1 beta produced time- and concentration-dependent stimulation of prostanoid biosynthesis [prostaglandin (PG)E2 and 6-keto-PGF1alpha]. Synergistic stimulation of prostanoid biosynthesis was demonstrated when BK or thrombin were added together with IL-1 alpha or -1 beta. BK and IL-1 beta both significantly stimulated the release of [3H]arachidonic acid. No synergistic effect on [3H]arachidonic acid release was seen when BK and IL-1 beta were added simultaneously. These data suggest that the synergistic effect of BK and IL-1 beta on prostanoid biosynthesis is not due to interactions at the receptor level nor to enhanced release of arachidonic acid, but may be due to increased activity of cyclo-oxygenase. Also, TNF-alpha and -beta produced a concentration-dependent stimulation of PGE2 formation in cultured human PDL cells. Synergistic effects of BK and thrombin were demonstrated when PGE2 production was stimulated in combination with TNF-beta. In addition, a synergistic effect on the PGE2 response to IL-1 alpha or -1 beta was demonstrated when added in combination with TNF-alpha. These experiments demonstrate synergistic interactions between BK, thrombin, IL-1 and TNF on prostaglandin biosynthesis in cultured human PDL cells. The findings suggest that inflammatory mediators may act in concert in stimulating prostanoid production in response to pro-inflammatory stimuli. As an inflammatory reaction is seen in the periodontal ligament when teeth are orthodontically treated, this

  3. Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering from Genital Neoplasia

    Science.gov (United States)

    Hajia, Massoud; Sohrabi, Amir

    2018-03-27

    Objective: Persistence of HPV infection is the true cause of cervical disorders. It is reported that competition may exist among HPV genotypes for colonization. This survey was designed to establish the multiple HPV genotype status in our community and the probability of multiple HPV infections involvement. Methods: All multiple HPV infections were selected for investigation in women suffering from genital infections referred to private laboratories in Tehran, Iran. A total of 160 multi HPV positive specimens from cervical scraping were identified by the HPV genotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV 6 (LR), 16 (HR), 53 (pHR), 31 (HR) and 11 (LR) were included in 48.8% of detected infections as the most five dominant genotypes. HPV 16 was detected at the highest rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51 and 56 in concurrent infections. It appears that HPV 16 and 53 may have significant tendencies to associate with each other rather than with other genotypes. Analysis of the data revealed there may be some synergistic interactions with a few particular genotypes such as "HPV 53". Conclusion: Multiple HPV genotypes appear more likely to be linked with development of cervical abnormalities especially in patients with genital infections. Since, there are various patterns of dominant HPV genotypes in different regions of world, more investigations of this type should be performed for careHPV programs in individual countries. Creative Commons Attribution License

  4. Insect nicotinic receptor interactions in vivo with neonicotinoid, organophosphorus, and methylcarbamate insecticides and a synergist

    Science.gov (United States)

    Shao, Xusheng; Xia, Shanshan; Durkin, Kathleen A.; Casida, John E.

    2013-01-01

    The nicotinic acetylcholine (ACh) receptor (nAChR) is the principal insecticide target. Nearly half of the insecticides by number and world market value are neonicotinoids acting as nAChR agonists or organophosphorus (OP) and methylcarbamate (MC) acetylcholinesterase (AChE) inhibitors. There was no previous evidence for in vivo interactions of the nAChR agonists and AChE inhibitors. The nitromethyleneimidazole (NMI) analog of imidacloprid, a highly potent neonicotinoid, was used here as a radioligand, uniquely allowing for direct measurements of house fly (Musca domestica) head nAChR in vivo interactions with various nicotinic agents. Nine neonicotinoids inhibited house fly brain nAChR [3H]NMI binding in vivo, corresponding to their in vitro potency and the poisoning signs or toxicity they produced in intrathoracically treated house flies. Interestingly, nine topically applied OP or MC insecticides or analogs also gave similar results relative to in vivo nAChR binding inhibition and toxicity, but now also correlating with in vivo brain AChE inhibition, indicating that ACh is the ultimate OP- or MC-induced nAChR active agent. These findings on [3H]NMI binding in house fly brain membranes validate the nAChR in vivo target for the neonicotinoids, OPs and MCs. As an exception, the remarkably potent OP neonicotinoid synergist, O-propyl O-(2-propynyl) phenylphosphonate, inhibited nAChR in vivo without the corresponding AChE inhibition, possibly via a reactive ketene metabolite reacting with a critical nucleophile in the cytochrome P450 active site and the nAChR NMI binding site. PMID:24108354

  5. Compatibility of spinosad with predaceous mites (Acari) used to control Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).

    Science.gov (United States)

    Rahman, Touhidur; Spafford, Helen; Broughton, Sonya

    2011-08-01

    Spinosad is a biopesticide widely used for control of Frankliniella occidentalis (Pergande). It is reported to be non-toxic to several predatory mite species used for the biological control of thrips. Predatory mites Typhlodromips montdorensis (Schicha), Neoseiulus cucumeris (Oudemans) and Hypoaspis miles (Berlese) have been used for control of F. occidentalis. This study investigated the impact of direct and residual toxicity of spinosad on F. occidentalis and predatory mites. The repellency of spinosad residues to these predatory mites was also investigated. Direct contact to spinosad effectively reduced the number of F. occidentalis adults and larvae, causing > 96% mortality. Spinosad residues aged 2-96 h were also toxic to F. occidentalis. Direct exposure to spinosad resulted in > 90% mortality of all three mite species. Thresholds for the residual toxicity (contact) of spinosad (LT25 ) were estimated as 4.2, 3.2 and 5.8 days for T. montdorensis, N. cucumeris and H. miles respectively. When mites were simultaneously exposed to spinosad residues and fed spinosad-intoxicated thrips larvae, toxicity increased. Residual thresholds were re-estimated as 5.4, 3.9 and 6.1 days for T. montdorensis, N. cucumeris and H. miles respectively. Residues aged 2-48 h repelled T. montdorensis and H. miles, and residues aged 2-24 h repelled N. cucumeris. Predatory mites can be safely released 6 days after spinosad is applied for the management of F. occidentalis. Copyright © 2011 Society of Chemical Industry.

  6. Use of Synergistic Interactions to Fabricate Strong, Tough, and Conductive Artificial Nacre Based on Graphene Oxide and Chitosan.

    Science.gov (United States)

    Wan, Sijie; Peng, Jingsong; Li, Yuchen; Hu, Han; Jiang, Lei; Cheng, Qunfeng

    2015-10-27

    Graphene is the strongest and stiffest material, leading to the development of promising applications in many fields. However, the assembly of graphene nanosheets into macrosized nanocomposites for practical applications remains a challenge. Nacre in its natural form sets the "gold standard" for toughness and strength, which serves as a guide to the assembly of graphene nanosheets into high-performance nanocomposites. Here we show the strong, tough, conductive artificial nacre based on graphene oxide through synergistic interactions of hydrogen and covalent bonding. Tensile strength and toughness was 4 and 10 times higher, respectively, than that of natural nacre. The exceptional integrated strong and tough artificial nacre has promising applications in aerospace, artificial muscle, and tissue engineering, especially for flexible supercapacitor electrodes due to its high electrical conductivity. The use of synergistic interactions is a strategy for the development of high-performance nanocomposites.

  7. Enhanced Biofilm Formation and Increased Resistance to Antimicrobial Agents and Bacterial Invasion Are Caused by Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Burmølle, Mette; Webb, J.S.; Rao, D.

    2006-01-01

    from the surface of the marine alga Ulva australis, were screened for synergistic interactions within biofilms when present together in different combinations. Four isolates, Microbacterium phyllosphaerae, Shewanella japonica, Dokdonia donghaensis, and Acinetobacter lwoffii, were found to interact......-species biofilms resisted invasion to a greater extent than did the biofilms formed by the single species. Replacement of each strain by its cell-free culture supernatant suggested that synergy was dependent both on species-specific physical interactions between cells and on extracellular secreted factors or less...

  8. Synergistic interaction and mode of action of Citrus hystrix essential oil against bacteria causing periodontal diseases.

    Science.gov (United States)

    Wongsariya, Karn; Phanthong, Phanida; Bunyapraphatsara, Nuntavan; Srisukh, Vimol; Chomnawang, Mullika Traidej

    2014-03-01

    Citrus hystrix de Candolle (Rutaceae), an edible plant regularly used as a food ingredient, possesses antibacterial activity, but there is no current data on the activity against bacteria causing periodontal diseases. C. hystrix essential oil from leaves and peel were investigated for antibiofilm formation and mode of action against bacteria causing periodontal diseases. In vitro antibacterial and antibiofilm formation activities were determined by broth microdilution and time kill assay. Mode of action of essential oil was observed by SEM and the active component was identified by bioautography and GC/MS. C. hystrix leaves oil exhibited antibacterial activity at the MICs of 1.06 mg/mL for P. gingivalis and S. mutans and 2.12 mg/mL for S. sanguinis. Leaf oil at 4.25 mg/mL showed antibiofilm formation activity with 99% inhibition. The lethal effects on P. gingivalis were observed within 2 and 4 h after treated with 4 × MIC and 2 × MIC, respectively. S. sanguinis and S. mutans were completely killed within 4 and 8 h after exposed to 4 × MIC and 2 × MIC of oil. MICs of tested strains showed 4 times reduction suggesting synergistic interaction of oil and chlorhexidine. Bacterial outer membrane was disrupted after treatment with leaves oil. Additionally, citronellal was identified as the major active compound of C. hystrix oil. C. hystrix leaf oil could be used as a natural active compound or in combination with chlorhexidine in mouthwash preparations to prevent the growth of bacteria associated with periodontal diseases and biofilm formation.

  9. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis.

    Directory of Open Access Journals (Sweden)

    Jingyue Xu

    Full Text Available Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not well understood, however. In this study, by using the recently developed CRISPR genome editing technology, we genetically labeled the endogenous Osr1 protein and show that Osr1 interacts with Wt1 in the developing kidney. Whereas mice heterozygous for either an Osr1 or Wt1 null allele have normal kidneys at birth, most mice heterozygous for both Osr1 and Wt1 exhibit defects in metanephric kidney development, including unilateral or bilateral kidney agenesis or hypoplasia. The developmental defects in the Osr1+/-Wt1+/- mouse embryos were detected as early as E10.5, during specification of the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells. Moreover, expression of Gdnf, the major nephrogenic signal for inducing ureteric bud outgrowth, was significantly reduced in the metanephric mesenchyme in Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- littermates. By E11.5, as the ureteric buds invade the metanephric mesenchyme and initiate branching morphogenesis, kidney morphogenesis was significantly impaired in the Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- embryos. These results indicate that Osr1 and Wt1 act synergistically to regulate nephron endowment by controlling metanephric mesenchyme specification during early nephrogenesis.

  10. Synergistic interaction between diene valepotriates from Valeriana glechomifolia Meyer (Valerianaceae) and classical antidepressants: an isobolographic analysis.

    Science.gov (United States)

    Müller, Liz G; Stolz, Eveline D; Betti, Andresa H; Herzfeldt, Vivian; Rates, Stela M K

    2015-07-01

    Combinations of different classes of antidepressants (including herbal adjuvants) have been used as an alternative means of achieving better results in the treatment of depressed patients. However, studies characterizing the interactions between herbal adjuvants and antidepressants are lacking. This study is the first to investigate the interaction between diene valepotriates (VAL) from Valeriana glechomifolia, a species with antidepressant-like effects, and imipramine (IMI), desipramine (DESI) and bupropion (BUP). The interactions were assessed via isobolographic analyses, which represent a tool for evaluating interactions between drugs. The interaction between VAL and each antidepressant was evaluated in mice given concurrent oral administration of each drug with fixed ED50 ratios and subjected to a forced swimming test (FST). Spontaneous locomotion was measured in the open field test. The drug combinations produced a dose-dependent anti-immobility effect in the FST without altering mouse locomotor activity. Isobolographic analysis revealed that VAL resulted in synergistic interactions in combination with each of the antidepressants tested. The synergistic interactions between VAL and IMI, DESI and BUP highlight the potential for VAL to serve as adjuvants to antidepressant drugs and suggest that VAL does not directly target the same sites on neuronal transporters as the antidepressants. © 2015 Royal Pharmaceutical Society.

  11. Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug-Polymer-Polymer Ternary Solution.

    Science.gov (United States)

    Prasad, Dev; Chauhan, Harsh; Atef, Eman

    2016-03-07

    We are reporting a synergistic effect of combined Eudragit E100 and PVP K90 in precipitation inhibition of indomethacin (IND) in solutions at low polymer concentration, a phenomenon that has significant implications on the usefulness of developing novel ternary solid dispersion of poorly soluble drugs. The IND supersaturation was created by cosolvent technique, and the precipitation studies were performed in the absence and the presence of individual and combined PVP K90 and Eudragit E100. The studies were also done with PEG 8000 as a noninteracting control polymer. A continuous UV recording of the IND absorption was used to observe changes in the drug concentration over time. The polymorphic form and morphology of precipitated IND were characterized by Raman spectroscopy and scanning electron microscopy. The change in the chemical shift in solution (1)H NMR was used as novel approach to probe IND-polymer interactions. Molecular modeling was used for calculating binding energy between IND-polymer as another indication of IND-polymer interaction. Spontaneous IND precipitation was observed in the absence of polymers. Eudragit E100 showed significant inhibitory effect on nuclei formation due to stronger interaction as reflected in higher binding energy and greater change in chemical shift by NMR. PVP K90 led to significant crystal growth inhibition due to adsorption on growing IND crystals as confirmed by modified crystal habit of precipitate in the presence of PVP K90. Combination of polymers resulted in a synergistic precipitation inhibition and extended supersaturation. The NMR confirmed interaction between IND-Eudragit E100 and IND-PVP K90 in solution. The combination of polymers showed similar peak shift albeit using lower polymer concentration indicating stronger interactions. The results established the significant synergistic precipitation inhibition effect upon combining Eudragit E100 and PVP K90 due to drug-polymer interaction.

  12. Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

    Directory of Open Access Journals (Sweden)

    Stuart J Grice

    2015-03-01

    Full Text Available Autism spectrum disorders (ASDs are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs. These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our

  13. Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

    Science.gov (United States)

    Grice, Stuart J; Liu, Ji-Long; Webber, Caleb

    2015-03-01

    Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates

  14. Coupling of Spinosad Fermentation and Separation Process via Two-Step Macroporous Resin Adsorption Method.

    Science.gov (United States)

    Zhao, Fanglong; Zhang, Chuanbo; Yin, Jing; Shen, Yueqi; Lu, Wenyu

    2015-08-01

    In this paper, a two-step resin adsorption technology was investigated for spinosad production and separation as follows: the first step resin addition into the fermentor at early cultivation period to decrease the timely product concentration in the broth; the second step of resin addition was used after fermentation to adsorb and extract the spinosad. Based on this, a two-step macroporous resin adsorption-membrane separation process for spinosad fermentation, separation, and purification was established. Spinosad concentration in 5-L fermentor increased by 14.45 % after adding 50 g/L macroporous at the beginning of fermentation. The established two-step macroporous resin adsorption-membrane separation process got the 95.43 % purity and 87 % yield for spinosad, which were both higher than that of the conventional crystallization of spinosad from aqueous phase that were 93.23 and 79.15 % separately. The two-step macroporous resin adsorption method has not only carried out the coupling of spinosad fermentation and separation but also increased spinosad productivity. In addition, the two-step macroporous resin adsorption-membrane separation process performs better in spinosad yield and purity.

  15. Antibacterial/Antifungal Activity and Synergistic Interactions between Polyprenols and Other Lipids Isolated from Ginkgo Biloba L. Leaves

    Directory of Open Access Journals (Sweden)

    Ran Tao

    2013-02-01

    Full Text Available Polyprenols separated from lipids are promising new components from Ginkgo biloba L. leaves (GBL. In this paper, ginkgo lipids were isolated by extraction with petroleum ether, saponification, and molecular distillation. Eight known compounds: isophytol (1, nerolidol (2, linalool (3, β-sitosterol acetate (4, β-sitosterol (5, stigmasterol (6, ergosterol (7, β-sitosterol-3-O-β-D-glucopyranoside (8 and Ginkgo biloba polyprenols (GBP were separated from GBL by chromatography and identified mainly by NMR. The separated and identified compounds 1, 2 and 3 are reported here for the first time in GBL. The 3D-DAD-HPLC-chromatogram (190–232 nm of GBP was recorded. This study provides new evidence as there are no previous reports on antibacterial/antifungal activities and synergistic interactions between GBP and the compounds separated from GBL lipids against Salmonella enterica, Staphylocococus aureus and Aspergillus niger. Nerolidol (2 showed the highest activity among all the tested samples and of all mixture groups tested the GBP with isophytol (1 mixture had the strongest synergistic effect against Salmonella enterica among the three tested strains. A proportion of isophytol and GBP of 38.19%:61.81% (wt/wt was determined by mixture design as the optimal proportion for the synergistic effect of GBP with isophytol against Salmonella enterica.

  16. An In Vitro Synergistic Interaction of Combinations of Thymus glabrescens Essential Oil and Its Main Constituents with Chloramphenicol

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    Budimir S. Ilić

    2014-01-01

    Full Text Available The chemical composition and antibacterial activity of Thymus glabrescens Willd. (Lamiaceae essential oil were examined, as well as the association between it and chloramphenicol. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, individually and in combination with chloramphenicol, were also determined. The interactions of the essential oil, geraniol, and thymol with chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil, with geraniol (22.33% as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antibiotic and thymol. A combination of  T. glabrescens oil and chloramphenicol produced a strong synergistic interaction (FIC indices in the range 0.21–0.87 and a substantial reduction of the MIC value of chloramphenicol, thus minimizing its adverse side effects. The combinations geraniol-chloramphenicol and thymol-chloramphenicol produced synergistic interaction to a greater extent, compared with essential oil-chloramphenicol association, which may indicate that the activity of the thyme oil could be attributed to the presence of significant concentrations of geraniol and thymol.

  17. THE SIDE-EFFECT OF ORGANIC INSECTICIDE SPINOSAD ON BIOCHEMICAL AND MICROBIOLOGICAL PROPERTIES OF CLAY SOIL

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    Arkadiusz Telesiński

    2015-09-01

    Full Text Available The aim of the study was to determine the effect of spinosad on soil biochemical and microbiological properties. The experiment was carried out on sandy loam with Corg content 10.91 g·kg-l. Spinosad, as Spintor 240 SC was added into soil in dosages: a recommended field dosage, and fivefold, tenfold, and twenty-fivefold higher dosages. The amount of spinosad introduced into soil was between 12.55 and 313.75 g·kg-l. Moreover, soil samples without spinosad supplement were prepared as a reference. Respective Spintor 240 SC doses were converted into 1 kg soil, taking into account 10 cm depth. After application of insecticide water emulsions, soil moisture was brought to 60% maximum holding water capacity. The soil was thoroughly mixed and stored in tightly-closed polyethylene bags at 20 °C for a period 4 weeks. During the experiment dissipation of spinosad, soil enzymes (dehydrogenase, alkaline phosphatase, acid phosphatase, urease and number of bacteria, fungi, actinomycetes were assayed. Obtained results showed, that dissipation of spinosad in soil was relatively fast – the DT50 of this insecticide was ranged between 1.11 and 2.21 days. Spinosad residues had different effects on soil microbiological and biochemical properties. However, over time the impact of this insecticide definitely decreased. This indicated that the use of spinosad in organic farming, particularly in the field dosage, does not pose a long-term threat to the soil environment.

  18. Synergistic interaction between total glucosides and total flavonoids on chronic constriction injury induced neuropathic pain in rats.

    Science.gov (United States)

    Zhang, Juan; Lv, Chen; Wang, Hai-na; Cao, Yi

    2013-04-01

    Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain. To investigate the synergistic potential of total glucosides of Paeoniae Radix (TGP) and total flavonoids of Glycyrrhizae Radix (TFL). Oral administration of TGP and TFL alone at the doses of 60,120 and 240 mg/kg or in combination were given only one time to the neuropathic pain rat induced by chronic constriction injury. Paw pressure and heat immersion tests were performed to assess degrees of mechanical allodynia and thermal hyperalgesia, respectively. Synergistic interactions between TGP and TFL were characterized using isobolographic analysis. Expressions of Sirt1 protein were detected by immunohistochemistry. On day 14 after surgery, single oral administration of TGP and TFL both produced significant anti-allodynic and anti-hyperalgesic effects in dose-dependent and time-dependent manners. The ED(50) value of TGP was 249.4 ± 10.8 mg/kg while TFL was 871.4 ± 30.5 mg/kg. Isobolographic analysis revealed that the combination of TGP with TFL at the fixed ratios of 3:1 exerted the highest sub-additive (synergistic) interaction, of which the experimental ED(50) value was 95.1 ± 9.0 mg/kg. SGD could also downregulate Sirt1 protein expression, which was 4.2-fold higher than that of model rats in dorsal root ganglion. Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.

  19. Monitoring Resistance to Spinosad in the Melon Fly (Bactrocera cucurbitae in Hawaii and Taiwan

    Directory of Open Access Journals (Sweden)

    Ju-Chun Hsu

    2012-01-01

    Full Text Available Spinosad is a natural insecticide with desirable qualities, and it is widely used as an alternative to organophosphates for control of pests such as the melon fly, Bactrocera cucurbitae (Coquillett. To monitor the potential for development of resistance, information about the current levels of tolerance to spinosad in melon fly populations were established in this study. Spinosad tolerance bioassays were conducted using both topical applications and feeding methods on flies from field populations with extensive exposure to spinosad as well as from collections with little or no prior exposure. Increased levels of resistance were observed in flies from the field populations. Also, higher dosages were generally required to achieve specific levels of mortality using topical applications compared to the feeding method, but these levels were all lower than those used for many organophosphate-based food lures. Our information is important for maintaining effective programs for melon fly management using spinosad.

  20. Synergistic interaction between mazindol, an anorectic drug, and swim-stress on analgesic responses in the formalin test in mice.

    Science.gov (United States)

    Vendruscolo, Leandro Franco; Takahashi, Reinaldo Naoto

    2004-01-23

    The present study examined the interaction between mazindol (MZ), an anorectic drug extensively used in Brazil and opioid/non-opioid endogenous analgesic systems activated by swim-stress. Further, the role of opioid, dopamine and N-methyl-D-aspartate (NMDA) receptors in mediating the analgesic effect was evaluated. The stress-induced analgesia of a 3-min swimming at 32 degrees C (opioid/non-opioid) and 20 degrees C (non-opioid) were assessed using the formalin test. Male Swiss mice were intraperitoneally injected with naloxone (1.0 mg/kg), sulpiride (3.0 mg/kg), MK-801 (0.075 mg/kg) or saline/vehicle 15 min prior, and with MZ (0.5 mg/kg) or saline/vehicle 5 min prior to swimming. The dose of MZ (0.5 mg/kg) did not cause analgesic effect, however, the association of MZ and swim-stress at both temperatures displayed synergistic interaction on analgesia that was blocked by sulpiride and MK-801 but not by naloxone. The present results suggest that MZ and swim-stress acted synergistically on analgesic responses, involving mainly the non-opioid component and possibly mediated by dopamine D2 receptors and NMDA receptors.

  1. Antimicrobial activity of nisin against the swine pathogen Streptococcus suis and its synergistic interaction with antibiotics.

    Science.gov (United States)

    Lebel, Geneviève; Piché, Fanny; Frenette, Michel; Gottschalk, Marcelo; Grenier, Daniel

    2013-12-01

    Streptococcus suis serotype 2 is known to cause severe infections in pigs, including meningitis, endocarditis and pneumonia. Furthermore, this bacterium is considered an emerging zoonotic agent. Recently, increased antibiotic resistance in S. suis has been reported worldwide. The objective of this study was to evaluate the potential of nisin, a bacteriocin of the lantibiotic class, as an antibacterial agent against the pathogen S. suis serotype 2. In addition, the synergistic activity of nisin in combination with conventional antibiotics was assessed. Using a plate assay, the nisin-producing strain Lactococcus lactis ATCC 11454 proved to be capable of inhibiting the growth of S. suis (n=18) belonging to either sequence type (ST)1, ST25, or ST28. In a microdilution broth assay, the minimum inhibitory concentration (MIC) of purified nisin ranged between 1.25 and 5 μg/mL while the minimum bactericidal concentration (MBC) was between 5 and 10 μg/mL toward S. suis. The use of a capsule-deficient mutant of S. suis indicated that the presence of this polysaccharidic structure has no marked impact on susceptibility to nisin. Following treatment of S. suis with nisin, transmission electron microscopy observations revealed lysis of bacteria resulting from breakdown of the cell membrane. A time-killing curve showed a rapid bactericidal activity of nisin. Lastly, synergistic effects of nisin were observed in combination with several antibiotics, including penicillin, amoxicillin, tetracycline, streptomycin and ceftiofur. This study brought clear evidence supporting the potential of nisin for the prevention and treatment of S. suis infections in pigs. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

    Science.gov (United States)

    Cea, Michele; Soncini, Debora; Fruscione, Floriana; Raffaghello, Lizzia; Garuti, Anna; Emionite, Laura; Moran, Eva; Magnone, Mirko; Zoppoli, Gabriele; Reverberi, Daniele; Caffa, Irene; Salis, Annalisa; Cagnetta, Antonia; Bergamaschi, Micaela; Casciaro, Salvatore; Pierri, Ivana; Damonte, Gianluca; Ansaldi, Filippo; Gobbi, Marco; Pistoia, Vito; Ballestrero, Alberto; Patrone, Franco; Bruzzone, Santina; Nencioni, Alessio

    2011-01-01

    Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD(+)-independent HDACs are an established therapeutic target, the relevance of NAD(+)-dependent HDACs (sirtuins) in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+)-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527) and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+) levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+)-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

  3. Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Michele Cea

    Full Text Available Aberrant histone deacetylase (HDAC activity is frequent in human leukemias. However, while classical, NAD(+-independent HDACs are an established therapeutic target, the relevance of NAD(+-dependent HDACs (sirtuins in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527 and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

  4. Interaction and its induced inhibiting or synergistic effects during co-gasification of coal char and biomass char.

    Science.gov (United States)

    Ding, Liang; Zhang, Yongqi; Wang, Zhiqing; Huang, Jiejie; Fang, Yitian

    2014-12-01

    Co-gasification of coal char and biomass char was conducted to investigate the interactions between them. And random pore model (RPM) and modified random pore model (MRPM) were applied to describe the gasification behaviors of the samples. The results show that inhibiting effect was observed during co-gasification of corn stalk char with Hulunbeier lignite coal char, while synergistic effects were observed during co-gasification of corn stalk char with Shenmu bituminous coal char and Jincheng anthracite coal char. The inhibiting effect was attributed to the intimate contact and comparable gasification rate between biomass char and coal char, and the loss of the active form of potassium caused by the formation of KAlSiO4, which was proved to be inactive during gasification. While the synergistic effect was caused by the high potassium content of biomass char and the significant difference of reaction rate between coal char and biomass char during gasification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant againstStaphylococcus aureus.

    Science.gov (United States)

    Umerska, Anita; Cassisa, Viviane; Bastiat, Guillaume; Matougui, Nada; Nehme, Hassan; Manero, Florence; Eveillard, Matthieu; Saulnier, Patrick

    2017-01-01

    Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of S. aureus , independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%-62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against S. aureus , as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against S. aureus , including MRSA.

  6. Synergistic interaction of gamma rays and some metallic salts in the induction of chlorophyll mutations in rice

    International Nuclear Information System (INIS)

    Reddy, T.P.; Vaidyanath, K.

    1978-01-01

    In this study the mutagenic activity of 9 metallic salts was tested in comparison and conjunction with gamma rays on rice seed. In M 2 , barium and cadmium produced chlorophyll mutation and mutant frequencies on a par with those of 20 kR gamma rays. Similarly, copper and mercury induced moderately high mutation and mutant frequencies. Salts of strontium, iron and lead showed rather weak mutagenic effects. On the other hand, two metals - manganese anc calcium - failed to provoke chlorophyll mutations in rice seed. Sequential treatments of gamma rays + 5 metals, namely Sr, Cd, Hg, Pb and Cu, produced synergistic yields of chlorophyll mutants in the M 2 generation. Two genetically active metals, Ba and Fe, showed less than additive effects when post-treated after gamma irradiation. Manganese, which failed to induce chlorophyll mutations in independent treatment, potentiated the mutagenic activity of gamma radiation in sequential treatment. On the other hand, sequential treatment with calcium seemed to confer a substantial protection against gamma-ray-induced genetic lesions. The probable mechanisms of synergistic interaction, mutagenic potentiation and protection, observed in sequential treatments, are discussed. (Auth.)

  7. Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.

    Science.gov (United States)

    Montiel-Ruiz, Rosa Mariana; González-Trujano, María Eva; Déciga-Campos, Myrna

    2013-11-15

    In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila.

    Science.gov (United States)

    Ku, Hsueh-Yen; Gangaraju, Vamsi K; Qi, Hongying; Liu, Na; Lin, Haifan

    2016-01-01

    Piwi proteins associate with piRNAs and functions in epigenetic programming, post-transcriptional regulation, transposon silencing, and germline development. However, it is not known whether the diverse functions of these proteins are molecularly separable. Here we report that Piwi interacts with Tudor-SN (Tudor staphylococcal nuclease, TSN) antagonistically in regulating spermatogenesis but synergistically in silencing transposons. However, it is not required for piRNA biogenesis. TSN is known to participate in diverse molecular functions such as RNAi, degradation of hyper-edited miRNAs, and spliceosome assembly. We show that TSN colocalizes with Piwi in primordial germ cells (PGCs) and embryonic somatic cells. In adult ovaries and testes, TSN is ubiquitously expressed and enriched in the cytoplasm of both germline and somatic cells. The tsn mutants display a higher mitotic index of spermatogonia, accumulation of spermatocytes, defects in meiotic cytokinesis, a decreased number of spermatids, and eventually reduced male fertility. Germline-specific TSN-expression analysis demonstrates that this function is germline-dependent. Different from other known Piwi interters, TSN represses Piwi expression at both protein and mRNA levels. Furthermore, reducing piwi expression in the germline rescues tsn mutant phenotype in a dosage-dependent manner, demonstrating that Piwi and TSN interact antagonistically in germ cells to regulate spermatogenesis. However, the tsn deficiency has little, if any, impact on piRNA biogenesis but displays a synergistic effect with piwi mutants in transposon de-silencing. Our results reveal the biological function of TSN and its contrasting modes of interaction with Piwi in spermatogenesis, transposon silencing, and piRNA biogenesis.

  9. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila.

    Directory of Open Access Journals (Sweden)

    Hsueh-Yen Ku

    2016-01-01

    Full Text Available Piwi proteins associate with piRNAs and functions in epigenetic programming, post-transcriptional regulation, transposon silencing, and germline development. However, it is not known whether the diverse functions of these proteins are molecularly separable. Here we report that Piwi interacts with Tudor-SN (Tudor staphylococcal nuclease, TSN antagonistically in regulating spermatogenesis but synergistically in silencing transposons. However, it is not required for piRNA biogenesis. TSN is known to participate in diverse molecular functions such as RNAi, degradation of hyper-edited miRNAs, and spliceosome assembly. We show that TSN colocalizes with Piwi in primordial germ cells (PGCs and embryonic somatic cells. In adult ovaries and testes, TSN is ubiquitously expressed and enriched in the cytoplasm of both germline and somatic cells. The tsn mutants display a higher mitotic index of spermatogonia, accumulation of spermatocytes, defects in meiotic cytokinesis, a decreased number of spermatids, and eventually reduced male fertility. Germline-specific TSN-expression analysis demonstrates that this function is germline-dependent. Different from other known Piwi interters, TSN represses Piwi expression at both protein and mRNA levels. Furthermore, reducing piwi expression in the germline rescues tsn mutant phenotype in a dosage-dependent manner, demonstrating that Piwi and TSN interact antagonistically in germ cells to regulate spermatogenesis. However, the tsn deficiency has little, if any, impact on piRNA biogenesis but displays a synergistic effect with piwi mutants in transposon de-silencing. Our results reveal the biological function of TSN and its contrasting modes of interaction with Piwi in spermatogenesis, transposon silencing, and piRNA biogenesis.

  10. Synergistic interactions of begomoviruses with Sweet potato chlorotic stunt virus (genus Crinivirus) in sweet potato (Ipomoea batatas L.).

    Science.gov (United States)

    Cuellar, Wilmer J; Galvez, Marco; Fuentes, Segundo; Tugume, Joab; Kreuze, Jan

    2015-06-01

    Three hundred and ninety-four sweet potato accessions from Latin America and East Africa were screened by polymerase chain reaction (PCR) for the presence of begomoviruses, and 46 were found to be positive. All were symptomless in sweet potato and generated leaf curling and/or chlorosis in Ipomoea setosa. The five most divergent isolates, based on complete genome sequences, were used to study interactions with Sweet potato chlorotic stunt virus (SPCSV), known to cause synergistic diseases with other viruses. Co-infections led to increased titres of begomoviruses and decreased titres of SPCSV in all cases, although the extent of the changes varied notably between begomovirus isolates. Symptoms of leaf curling only developed temporarily in combination with isolate StV1 and coincided with the presence of the highest begomovirus concentrations in the plant. Small interfering RNA (siRNA) sequence analysis revealed that co-infection of SPCSV with isolate StV1 led to relatively increased siRNA targeting of the central part of the SPCSV genome and a reduction in targeting of the genomic ends, but no changes to the targeting of StV1 relative to single infection of either virus. These changes were not observed in the interaction between SPCSV and the RNA virus Sweet potato feathery mottle virus (genus Potyvirus), implying specific effects of begomoviruses on RNA silencing of SPCSV in dually infected plants. Infection in RNase3-expressing transgenic plants showed that this protein was sufficient to mediate this synergistic interaction with DNA viruses, similar to RNA viruses, but exposed distinct effects on RNA silencing when RNase3 was expressed from its native virus, or constitutively from a transgene, despite a similar pathogenic outcome. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  11. Molecular spectroscopy and chemometrics: an analytical study of synergistic effects of drugs--interaction between fluoroquinolones and DNA.

    Science.gov (United States)

    Ni, Yongnian; Du, Shan; Kokot, Serge

    2009-09-01

    Three commonly used fluoroquinolone antibiotics (norfloxacin (NFX), ofloxacin (OFX) and lomefloxacin (LMFX)) were used as examples of molecules which can interact with a biomacromolecule, such as DNA, separately or in a mixture. Such interactions were investigated with the use of UV and Synchronous Fluorescence Spectroscopy (SFS). Equilibrium binding (K(ap)) and Stern-Volmer equilibrium (K(SV)) constants were extracted from these two types of spectra from interactions of DNA with single fluoroquinolones. The values of these equilibrium constants were relatively low, and this suggested that the DNA groove was the likely binding site. The complex SFS profiles obtained from the interactions of the DNA with the drug analyte mixtures were resolved, with the use of the curve resolution method, parallel factor (PARAFAC) analysis, into spectra of individual drugs. From these spectra, the (K(SV)) values for the individual analytes in the mixture were obtained. Also extracted were the concentrations of the individual quinolones as a function of concentration of the DNA. From a comparison of the equilibrium constants for the individual drug-DNA interaction with those obtained from the interaction with the drugs in a mixture, it was found that the binding strength of a single analyte to DNA was LMFX > NFX > OFX, but when the drug mixture was involved, this order was reversed. Importantly, it was also found that the equilibrium uptake of the drugs OFX and NFX was higher than from single drug-DNA experiments; the concentrations of LMFX did not change significantly. These observations collectively suggested that the binding of NFX and OFX to DNA is synergistically affected and that they probably share similar binding sites, while the LMFX was bound to a different site. This new important qualitative and quantitative information, which can now act as a springboard for more complex and deeper studies of the apparent synergistic effects of drug interactions with biomacromolecules

  12. Spinosad- and Deltamethrin-Induced Impact on Mating and Reproductive Output of the Maize Weevil Sitophilus zeamais.

    Science.gov (United States)

    Vélez, Mayra; Botina, Lorena L; Turchen, Leonardo M; Barbosa, Wagner F; Guedes, Raul Narciso C

    2018-01-20

    Assessments of acute insecticide toxicity frequently focus on the lethal effects on individual arthropod pest species and populations neglecting the impacts and consequences of sublethal exposure. However, the sublethal effects of insecticides may lead to harmful, neutral, or even beneficial responses that may affect (or not) the behavior and sexual fitness of the exposed insects. Intriguingly, little is known about such effects on stored product insect pests in general and the maize weevil in particular. Thus, we assessed the sublethal effects of spinosad and deltamethrin on female mate-searching, mating behavior, progeny emergence, and grain consumption by maize weevils. Insecticide exposure did not affect the resting time, number of stops, and duration of mate-searching by female weevils, but their walking velocity was compromised. Maize weevil couples sublethally exposed to deltamethrin and spinosad exhibited altered reproductive behavior (walking, interacting, mounting, and copulating), but deltamethrin caused greater impairment. Curiously, higher grain consumption and increased progeny emergence were observed in deltamethrin-exposed insects, suggesting that this pyrethroid insecticide elicits hormesis in maize weevils that may compromise control efficacy by this compound. Although spinosad has less of an impact on weevil reproductive behavior than deltamethrin, this bioinsecticide also benefited weevil progeny emergence, but did not affect grain consumption. Therefore, our findings suggest caution using either compound, and particularly deltamethrin, for controlling the maize weevil, as they may actually favor this species population growth when in sublethal exposure requiring further assessments. The same concern may be valid for other insecticides as well, what deserves future attention. © The Author(s) 2018. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Effects of spinosad on Helicoverpa armigera (Lepidoptera: Noctuidae) from China: tolerance status, synergism and enzymatic responses.

    Science.gov (United States)

    Wang, Dong; Qiu, Xinghui; Ren, Xuexiang; Zhang, Wencheng; Wang, Kaiyun

    2009-09-01

    Spinosad is increasingly used in pest management programmes, and resistance to it has been detected in recent years. However, there is no report on the susceptibilities of field populations of Helicoverpa armigera (Hübner) from China. Furthermore, the impact of spinosad on metabolic enzymes in this pest remains unknown. Four populations of H. armigera from different locations in China displayed less than 6.5-fold difference in LC(50) to spinosad, the highest being in the Xinjiang population, followed by Xiajin, Taian and Hubei populations, while there was no significant difference at LC(99) level among the four populations. The toxicity of spinosad could be synergised by piperonyl butoxide (PBO) and triphenylphosphate (TPP), but not by diethyl maleate (DEM). Spinosad exposure for 48 h significantly increased the activities of p-nitroanisole O-demethylase (ODM), while no significant changes in glutathione-S-transferase (GST) and carboxyl esterase (CarE) were observed. Field populations of H. armigera from China displayed marginally different susceptibilities to spinosad and had a relatively low LC(50). Cytochrome P450 monooxygenase might be involved in the metabolism of, and hence resistance to, spinosad in this pest in China. Copyright 2009 Society of Chemical Industry.

  14. Stability of spinosad resistance in Frankliniella occidentalis (Pergande) under laboratory conditions.

    Science.gov (United States)

    Bielza, P; Quinto, V; Grávalos, C; Fernández, E; Abellán, J; Contreras, J

    2008-08-01

    The stability of spinosad resistance in western flower thrips (WFT), Frankliniella occidentalis (Pergande), populations with differing initial frequencies of resistance was studied in laboratory conditions. The stability of resistance was assessed in bimonthly residual bioassays in five populations with initial frequencies of 100, 75, 50, 25 and 0% of resistant individuals. There were no consistent changes in susceptibility of the susceptible strain after eight months without insecticide pressure. In the resistant strain, very highly resistant to spinosad (RF50>23,000-fold), resistance was maintained up to eight months without further exposure to spinosad. In the absence of any immigration of susceptible genes into the population, resistance was stable. In the case of the population with different initial frequency of resistant thrips, spinosad resistance declined significantly two months later in the absence of selection pressure. With successive generations, these strains did not change significantly in sensitivity. Spinosad resistance in F. occidentalis declined significantly in the absence of selection pressure and the presence of susceptible WFT. These results suggest that spinosad resistance probably is unstable under field conditions, primarily due to the immigration of susceptible WFT. Factors influencing stability or reversion of spinosad resistance are discussed.

  15. THE ANTIBACTERIAL EFFECT OF SOME MEDICINAL PLANTS (INULA VISCOSA, ANACYCLUS VALENTINUS AND THEIR SYNERGISTIC INTERACTION WITH ANTIBIOTIC DRUGS

    Directory of Open Access Journals (Sweden)

    K. Side Larbi

    2016-05-01

    Full Text Available With the emergence of multidrug-resistant organisms, combining medicinal plants with synthetic medicines against resistant bacteria becomes necessary. In this study, Synergism between plant extracts (methanolic extract and essential oils of Inula viscosa and Anacyclus valentinus and two commonly used antibiotics (gentamycin, oxacillin were investigated on three bacterian strains (E. coli, Bacillus subtilis, Staphylococcus aureus. In the first time, the antibacterial effect of extracts alone was tested against 7 strains by disc diffusion and microdilution methods. The minimum inhibitory concentrations of methanolic extracts ranged between 6.25 and 50mg/ml while that of the essential oils varied between 12.5 and 100µL/mL. Interactions extracts /antibiotics and extracts/extracts by checkboard. The results show that the synergistic effect of combinations plant extracts/antibiotics was more important than extracts/extracts.

  16. Synergistic interaction between ankle and knee during hopping revealed through induced acceleration analysis.

    Science.gov (United States)

    João, Filipa; Veloso, António; Cabral, Sílvia; Moniz-Pereira, Vera; Kepple, Thomas

    2014-02-01

    The forces produced by the muscles can deliver energy to a target segment they are not attached to, by transferring this energy throughout the other segments in the chain. This is a synergistic way of functioning, which allows muscles to accelerate or decelerate segments in order to reach the target one. The purpose of this study was to characterize the contribution of each lower extremity joint to the vertical acceleration of the body's center of mass during a hopping exercise. To accomplish this, an induced acceleration analysis was performed using a model with eight segments. The results indicate that the strategies produced during a hopping exercise rely on the synergy between the knee and ankle joints, with most of the vertical acceleration being produced by the knee extensors, while the ankle plantar flexors act as stabilizers of the foot. This synergy between the ankle and the knee is perhaps a mechanism that allows the transfer of power from the knee muscles to the ground, and we believe that in this particular task the net action of the foot and ankle moments is to produce a stable foot with little overall acceleration. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Synergistic interactions between leaf beetle herbivory and fire enhance tamarisk (Tamarix spp.) mortality

    Science.gov (United States)

    Drus, Gail M.; Dudley, Tom L.; Antonio, Carla M.; Even, Thomas J.; Brooks, Matt L.; Matchett, J.R.

    2014-01-01

    The combined effects of herbivory and fire on plant mortality were investigated using prescribed burns of tamarisk (Tamarix ramosissima Lebed) exposed to herbivory by the saltcedar leaf beetle (Chrysomelidae: Diorhabda carinulata Desbrocher). Tamarix stands in the Humboldt Sink (NV, USA) were divided into three treatments: summer burn (August 2006), fall burn (October 2006) and control (unburned), and litter depth was manipulated to vary fire intensity within burn seasons. A gradient of existing herbivory impact was described with three plant condition metrics prior to fire: reduced proportions of green canopy, percent root crown starch sampled at the height of the growing season (August 2006), and percent root crown starch measured during dormancy (December 2006). August root crown starch concentration and proportion green canopy were strongly correlated, although the proportion green canopy predicted mortality better than August root crown starch. December root crown starch concentration was more depleted in unburned trees and in trees burned during the summer than in fall burn trees. Mortality in summer burned trees was higher than fall burned trees due to higher fire intensity, but December root crown starch available for resprouting in the spring was also lower in summer burned trees. The greatest mortality was observed in trees with the lowest December root crown starch concentration which were exposed to high fire intensity. Disproportionate changes in the slope and curvature of prediction traces as fire intensity and December starch reach reciprocal maximum and minimum levels indicate that beetle herbivory and fire intensity are synergistic.

  18. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

    Science.gov (United States)

    Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

    2017-03-01

    Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. Effect of Eugenol against Streptococcus agalactiae and Synergistic Interaction with Biologically Produced Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Renata Perugini Biasi-Garbin

    2015-01-01

    Full Text Available Streptococcus agalactiae (group B streptococci (GBS is an important infections agent in newborns associated with maternal vaginal colonization. Intrapartum antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant reduction in the incidence of early neonatal infection in various geographic regions. However, this strategy may lead to resistance selecting among GBS, indicating the need for new alternatives to prevent bacterial transmission and even to treat GBS infections. This study reported for the first time the effect of eugenol on GBS isolated from colonized women, alone and in combination with silver nanoparticles produced by Fusarium oxysporum (AgNPbio. Eugenol showed a bactericidal effect against planktonic cells of all GBS strains, and this effect appeared to be time-dependent as judged by the time-kill curves and viability analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic activity, significantly reducing the minimum inhibitory concentration values of both compounds. Scanning and transmission electron microscopy revealed fragmented cells and changes in bacterial morphology after incubation with eugenol. In addition, eugenol inhibited the viability of sessile cells during biofilm formation and in mature biofilms. These results indicate the potential of eugenol as an alternative for controlling GBS infections.

  20. Kinetic study and synergistic interactions on catalytic CO2 gasification of Sudanese lower sulphur petroleum coke and sugar cane bagasse

    Directory of Open Access Journals (Sweden)

    Elbager M.A. Edreis

    2017-04-01

    Full Text Available In this study the effects of iron chloride (FeCl3 on the CO2 gasification kinetics of lower sulphur petroleum coke (PC and sugar cane bagasse (SCB via thermogravimetric analyser (TGA were investigated. The FeCl3 loading effects on the thermal behaviour and reactivity of CO2 gasification of PC were studied. The possible synergistic interaction between the PC and SCB was also examined. Then the homogeneous model or first order chemical reaction (O1 and shrinking core models (SCM or phase boundary controlled reactions (R2 and R3 were employed through Coats–Redfern method in order to detect the optimum mechanisms for the catalytic CO2 gasification, describe the best reaction behaviour and determine the kinetic parameters. The results showed that the thermal behaviour of PC is significantly affected by the FeCl3 loading. Among various catalyst loadings, the addition of 7 wt% FeCl3 to PC leads to improve the PC reactivity up to 39% and decrease the activation energy up to 22%. On the other hand, for char gasification stage of SCB and blend, the addition 5 wt% FeCl3 improved their reactivities to 18.7% and 29.8% and decreased the activation energies to 10% and 17%, respectively. The synergistic interaction between the fuel blend was observed in both reaction stages of the blend and became more significant in the pyrolysis stage. For all samples model R2 shows the lowest values of activation energy (E and the highest reaction rates constant (k. Finally, model R2 was the most suitable to describe the reactions of non-catalytic and catalytic CO2 gasification.

  1. Work stress, worries, and pain interact synergistically with modelled traffic noise on cross-sectional associations with self-reported sleep problems.

    Science.gov (United States)

    Kristiansen, Jesper; Persson, Roger; Björk, Jonas; Albin, Maria; Jakobsson, Kristina; Ostergren, Per-Olof; Ardö, Jonas

    2011-02-01

    To examine the risk of sleep problems associated with work stress (job strain, job demands, and decision authority), worries and pain and to investigate the synergistic interaction between these factors and traffic noise. Sleep problems and predictor variables were assessed in a cross-sectional public health survey with 12,093 respondents. Traffic noise levels were assessed using modelled A-weighted energy equivalent traffic sound levels at the residence. The risk of sleep problems was modelled using multiple logistic regression analysis. With regard to sleep problems not attributed to any external source (general sleep problems), independent main effects were found for traffic noise (women), decision authority (women), job strain, job demands, suffering from pain or other afflictions, worries about losing the job, experiencing bullying at work, having troubles paying the bills, and having a sick, disabled, or old relative to take care of (women). Significant synergistic effects were found for traffic noise and experiencing bullying at work in women. With regard to sleep problems attributed to traffic noise, strong synergistic interactions were found between traffic noise and, respectively, job demands (men), having pain or other afflictions, taking care of a sick, old, or disabled relative, and having troubles paying the bills. Main effects were found for worries about losing the job, experiencing bullying at work, job strain (men), and decision authority (men). Synergistic interactions could potentially contribute with 10-20% of the sleep problems attributed to traffic noise in the population. Work stress, pain, and different worries were independently associated with general sleep problems and showed in general no synergistic interaction with traffic noise. In contrast, synergistic effects between traffic noise and psychological factors were found with regard to sleep problems attributed to traffic noise. The synergy may contribute significantly to sleep

  2. Influence of environmental factors on the response of a natural population of Daphnia magna (Crustacea: Cladocera) to spinosad and Bacillus thuringiensis israelensis in Mediterranean coastal wetlands

    International Nuclear Information System (INIS)

    Duchet, C.; Caquet, Th.; Franquet, E.; Lagneau, C.; Lagadic, L.

    2010-01-01

    The present study was undertaken to assess the impact of a candidate mosquito larvicide, spinosad (8, 17 and 33 μg L -1 ) on a field population of Daphnia magna under natural variations of water temperature and salinity, using Bti (0.16 and 0.50 μL L -1 ) as the reference larvicide. Microcosms (125 L) were placed in a shallow temporary marsh where D. magna was naturally present. The peak of salinity observed during the 21-day observation period may have been partly responsible for the decrease of daphnid population density in all the microcosms. It is also probably responsible for the absence of recovery in the microcosms treated with spinosad which caused a sharp decrease of D. magna abundance within the first two days following treatment whereas Bti had no effect. These results suggest that it may be difficult for a field population of daphnids to cope simultaneously with natural (water salinity and temperature) and anthropogenic (larvicides) stressors. - Significant interaction between salinity and spinosad exposure impairs the recovery of a natural population of Daphnia magna.

  3. Influence of environmental factors on the response of a natural population of Daphnia magna (Crustacea: Cladocera) to spinosad and Bacillus thuringiensis israelensis in Mediterranean coastal wetlands

    Energy Technology Data Exchange (ETDEWEB)

    Duchet, C. [Entente Interdepartementale de Demoustication du Littoral Mediterraneen, 165 avenue Paul-Rimbaud, Montpellier F-34184 (France); INRA, UMR985 Ecologie et Sante des Ecosystemes, Equipe Ecotoxicologie et Qualite des Milieux Aquatiques, 65 rue de Saint Brieuc, Rennes F-35042 (France); Caquet, Th. [INRA, UMR985 Ecologie et Sante des Ecosystemes, Equipe Ecotoxicologie et Qualite des Milieux Aquatiques, 65 rue de Saint Brieuc, Rennes F-35042 (France); Franquet, E. [Universite Paul Cezanne, Institut Mediterraneen d' Ecologie et de Paleoecologie, Faculte des Sciences et Techniques Saint Jerome, C31, Marseille F-13397 (France); Lagneau, C. [Entente Interdepartementale de Demoustication du Littoral Mediterraneen, 165 avenue Paul-Rimbaud, Montpellier F-34184 (France); Lagadic, L., E-mail: Laurent.Lagadic@rennes.inra.f [INRA, UMR985 Ecologie et Sante des Ecosystemes, Equipe Ecotoxicologie et Qualite des Milieux Aquatiques, 65 rue de Saint Brieuc, Rennes F-35042 (France)

    2010-05-15

    The present study was undertaken to assess the impact of a candidate mosquito larvicide, spinosad (8, 17 and 33 mug L{sup -1}) on a field population of Daphnia magna under natural variations of water temperature and salinity, using Bti (0.16 and 0.50 muL L{sup -1}) as the reference larvicide. Microcosms (125 L) were placed in a shallow temporary marsh where D. magna was naturally present. The peak of salinity observed during the 21-day observation period may have been partly responsible for the decrease of daphnid population density in all the microcosms. It is also probably responsible for the absence of recovery in the microcosms treated with spinosad which caused a sharp decrease of D. magna abundance within the first two days following treatment whereas Bti had no effect. These results suggest that it may be difficult for a field population of daphnids to cope simultaneously with natural (water salinity and temperature) and anthropogenic (larvicides) stressors. - Significant interaction between salinity and spinosad exposure impairs the recovery of a natural population of Daphnia magna.

  4. Autosomal male determination in a spinosad-resistant housefly strain from Denmark

    DEFF Research Database (Denmark)

    Højland, Dorte H; Scott, Jeffrey G; Vagn Jensen, Karl-Martin

    2014-01-01

    BACKGROUND The housefly, Musca domestica L., is a global pest and has developed resistance to most insecticides applied for its control. The insecticide spinosad plays an important role in housefly control. Females of the Danish housefly strain 791spin are threefold more resistant to spinosad than...... males in this strain. The factor responsible for spinosad resistance in the strain is unknown, but previous studies suggest a role of cytochrome P450s for detoxification of spinosad. Sex determination in the housefly is controlled by a male-determining factor (M), either located on the Y chromosome...... or on one of the five autosomes (I to V). RESULTS The authors performed a series of crosses and backcrosses, starting with cross of 791spin and the susceptible reference strain aabys (bearing morphological mutations on each autosome). These flies were evaluated for gender and bioassayed to determine levels...

  5. Toxicity of spinosad to temephos-resistant Aedes aegypti populations in Brazil

    Science.gov (United States)

    dos Santos Dias, Luciana; Macoris, Maria de Lourdes da Graça; Andrighetti, Maria Teresa Macoris; Otrera, Vanessa Camargo Garbeloto; Dias, Adriana dos Santos; Bauzer, Luiz Guilherme Soares da Rocha; Rodovalho, Cynara de Melo; Martins, Ademir Jesus; Lima, José Bento Pereira

    2017-01-01

    The mosquito Aedes aegypti is the primary vector of different arboviruses and represents a major public health problem. Several Brazilian populations of Ae. aegypti have developed resistance to temephos, the most used organophosphate larvicide. New tools which are less harmful to the environment and safer for humans are becoming increasingly important to control this insect vector. Spinosad, an aerobic fermentation product of a soil actinobacteria, has a favorable environmental profile. It presents selective insecticide properties, a mechanism of action that differs from those of many synthetic chemical insecticides. The toxicity of spinosad and temephos to Aedes aegypti populations from Brazil, which were previously exposed to temephos, were investigated in this study. Larval susceptibility (LC50) to temephos varied from 3μg/L for Rockefeller up to 260 μg/L for Santana do Ipanema field derived population. Larval susceptibility (LC50) to spinosad varied from 23μg/L for Rockefeller up to 93μg/L for Marilia field derived population. In addition, a semi-field trial was performed to evaluate spinosad (NatularTM DT) initial efficacy and persistence toward four field-derived lineages and the Rockefeller lineage, used as an internal control. Spinosad was tested at 0.5mg active ingredient/L in 200L capacity water tanks. Mortality was recorded each 24 hours after exposition and tanks were further recolonized once per week with mortality being recorded daily for eight weeks. Spinosad provided a level equal or superior to 80% mortality during a seven to eight week evaluation period. The assessed populations did not present cross-resistance between spinosad and temephos in laboratory conditions. It demonstrates that spinosad may be a promising larvicide for the control of Ae. aegypti, especially for populations in which resistance to temephos has been detected. PMID:28301568

  6. Toxicity of spinosad to temephos-resistant Aedes aegypti populations in Brazil.

    Directory of Open Access Journals (Sweden)

    Luciana Dos Santos Dias

    Full Text Available The mosquito Aedes aegypti is the primary vector of different arboviruses and represents a major public health problem. Several Brazilian populations of Ae. aegypti have developed resistance to temephos, the most used organophosphate larvicide. New tools which are less harmful to the environment and safer for humans are becoming increasingly important to control this insect vector. Spinosad, an aerobic fermentation product of a soil actinobacteria, has a favorable environmental profile. It presents selective insecticide properties, a mechanism of action that differs from those of many synthetic chemical insecticides. The toxicity of spinosad and temephos to Aedes aegypti populations from Brazil, which were previously exposed to temephos, were investigated in this study. Larval susceptibility (LC50 to temephos varied from 3μg/L for Rockefeller up to 260 μg/L for Santana do Ipanema field derived population. Larval susceptibility (LC50 to spinosad varied from 23μg/L for Rockefeller up to 93μg/L for Marilia field derived population. In addition, a semi-field trial was performed to evaluate spinosad (NatularTM DT initial efficacy and persistence toward four field-derived lineages and the Rockefeller lineage, used as an internal control. Spinosad was tested at 0.5mg active ingredient/L in 200L capacity water tanks. Mortality was recorded each 24 hours after exposition and tanks were further recolonized once per week with mortality being recorded daily for eight weeks. Spinosad provided a level equal or superior to 80% mortality during a seven to eight week evaluation period. The assessed populations did not present cross-resistance between spinosad and temephos in laboratory conditions. It demonstrates that spinosad may be a promising larvicide for the control of Ae. aegypti, especially for populations in which resistance to temephos has been detected.

  7. The interactive effects of ammonia and microcystin on life-history traits of the cladoceran Daphnia magna: synergistic or antagonistic?

    Directory of Open Access Journals (Sweden)

    Zhou Yang

    Full Text Available The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the life history of the model organism Daphnia magna. Ammonia and microcystin-LR treatments were: 0, 0.366, 0.581 mg L(-1 and 0, 10, 30, 100 µg L(-1, respectively. Experiments followed a fully factorial design. Incubations were 14 d and recorded the following life-history traits: number of moults, time to first batch of eggs, time to first clutch, size at first batch of eggs, size at first clutch, number of clutches per female, number of offspring per clutch, and total offspring per female. Both ammonia and microcystin were detrimental to most life-history traits. Interactive effects of the toxins occurred for five traits: the time to first batch of eggs appearing in the brood pouch, time to first clutch, size at first clutch, number of clutches, and total offspring per female. The interactive effects of ammonia and microcystin appeared to be synergistic on some parameters (e.g., time to first eggs and antagonistic on others (e.g., total offspring per female. In conclusion, the released toxins during the degradation of Microcystis blooms would result, according to our data, in substantially negative effect on D. magna.

  8. Synergistic interaction of sumac and raspberry mixtures in their antioxidant capacities and selective cytotoxicity against cancerous cells.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan; Marcone, Massimo F

    2015-03-01

    Previous works on staghorn sumac (Rhus hirta) were mostly dedicated to its phytochemical profiles, antioxidant properties, and antidiabetic potentials. This study explored the potential of staghorn-sumac-derived functional ingredients for food and pharmacological applications. Sumac may have other biological functions, such as inhibitory effect on cancerous cells independent of its antioxidant properties. We characterized sumac and raspberry interactions, and their antioxidant capacities (ACs) and their inhibitory effect on both normal and cancerous cells. Mixing sumac and raspberry extracts yielded significantly higher ACs than the sum of sumac and raspberry as evaluated by three in vitro AC assays. However, the potential use of staghorn sumac as a natural source of dietary antioxidant supplement for oxidative-stress-related disorders might be challenged by its cytotoxicity in culturing normal cells. Remarkably, mixing sumac and raspberry showed maximal inhibition of the growth of both rat colon and human breast cancer cells with relatively low cytotoxicity toward normal rat colon and human breast epithelial cells, as compared with sumac or raspberry treatment alone. Sumac-derived products and their synergistic interactions with other food ingredients have great promise as functional food or nutraceutical products that would target cancer cells with minimal toxic effects to normal cells.

  9. In vitro synergistic interaction between amphotericin B and pentamidine against Scedosporium prolificans.

    NARCIS (Netherlands)

    Afeltra, J.; Danaoui, E.; Meis, J.F.G.M.; Rodriguez-Tudela, J.L.; Verweij, P.E.

    2002-01-01

    To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical

  10. Fitness cost and realized heritability of resistance to spinosad in Chrysoperla carnea (Neuroptera: Chrysopidae).

    Science.gov (United States)

    Abbas, N; Mansoor, M M; Shad, S A; Pathan, A K; Waheed, A; Ejaz, M; Razaq, M; Zulfiqar, M A

    2014-12-01

    The common green lacewing Chrysoperla carnea is a key biological control agent employed in integrated pest management (IPM) programs for managing various insect pests. Spinosad is used for the management of pests in ornamental plants, fruit trees, vegetable and field crops all over the world, including Pakistan. A field-collected population of C. carnea was selected with spinosad and fitness costs and realized heritability were investigated. After selection for five generations, C. carnea developed 12.65- and 73.37-fold resistance to spinosad compared to the field and UNSEL populations. The resistant population had a relative fitness of 1.47, with substantially higher emergence rate of healthy adults, fecundity and hatchability and shorter larval duration, pupal duration, and development time as compared to a susceptible laboratory population. Mean relative growth rate of larvae, intrinsic rate of natural population increase and biotic potential was higher for the spinosad-selected population compared to the susceptible laboratory population. Chrysoperla species are known to show resistance to insecticides which makes the predator compatible with most IPM systems. The realized heritability (h 2) value of spinosad resistance was 0.37 in spinosad-selected population of C. carnea.

  11. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    Science.gov (United States)

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  12. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    Directory of Open Access Journals (Sweden)

    Aijaz Ahmad

    Full Text Available We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6 and tested their antifungal activity against different clinical fluconazole (FLC- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%, additive (41% or indifferent (23% interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  13. Functional behavior of bio-electrochemical treatment system with increasing azo dye concentrations: Synergistic interactions of biocatalyst and electrode assembly.

    Science.gov (United States)

    Sreelatha, S; Velvizhi, G; Naresh Kumar, A; Venkata Mohan, S

    2016-08-01

    Treatment of dye bearing wastewater through biological machinery is particularly challenging due to its recalcitrant and inhibitory nature. In this study, functional behavior and treatment efficiency of bio-electrochemical treatment (BET) system was evaluated with increasing azo dye concentrations (100, 200, 300 and 500mg dye/l). Maximum dye removal was observed at 300mg dye/l (75%) followed by 200mg dye/l (65%), 100mg dye/l (62%) and 500mg dye/l (58%). Concurrent increment in dye load resulted in enhanced azo reductase and dehydrogenase activities respectively (300mg dye/l: 39.6U; 4.96μg/ml). Derivatives of cyclic voltammograms also supported the involvement of various membrane bound redox shuttlers, viz., cytochrome-c, cytochrome-bc1 and flavoproteins during the electron transfer. Bacterial respiration during BET operation utilized various electron acceptors such as electrodes and dye intermediates with simultaneous bioelectricity generation. This study illustrates the synergistic interaction of biocatalyst with electrode assembly for efficient treatment of azo dye wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

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    Francesco Nazzi

    Full Text Available The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV, transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

  15. Competitive and Synergistic Interactions between Polymer Micelles, Drugs, and Cyclodextrins: The Importance of Drug Solubilization Locus.

    Science.gov (United States)

    Valero, Margarita; Castiglione, Franca; Mele, Andrea; da Silva, Marcelo A; Grillo, Isabelle; González-Gaitano, Gustavo; Dreiss, Cécile A

    2016-12-13

    Polymeric micelles, in particular PEO-PPO-based Pluronic, have emerged as promising drug carriers, while cyclodextrins (CD), cyclic oligosaccharides with an apolar cavity, have long been used for their capacity to form inclusion complexes with drugs. Dimethylated β-cyclodextrin (DIMEB) has the capacity to fully breakup F127 Pluronic micelles, while this effect is substantially hindered if drugs are loaded within the micellar aggregates. Four drugs were studied at physiological temperature: lidocaine (LD), pentobarbital sodium salt (PB), sodium naproxen (NP), and sodium salicylate (SAL); higher temperatures shift the equilibrium toward higher drug partitioning and lower drug/CD binding compared to 25 °C ( Valero, M.; Dreiss, C. A. Growth, Shrinking, and Breaking of Pluronic Micelles in the Presence of Drugs and/or β-Cyclodextrin, a Study by Small-Angle Neutron Scattering and Fluorescence Spectroscopy . Langmuir 2010 , 26 , 10561 - 10571 ). The impact of drugs on micellar structure was characterized by small-angle neutron scattering (SANS), while their solubilization locus was revealed by 2D NOESY NMR. UV and fluorescence spectroscopy, Dynamic and Static Light Scattering were employed to measure a range of micellar properties and drug:CD interactions: binding constant, drug partitioning within the micelles, critical micellar concentration of the loaded micelles, aggregation number (N agg ). Critically, time-resolved SANS (TR-SANS) reveal that micellar breakup in the presence of drugs is substantially slower (100s of seconds) than for the free micelles (<100 ms) ( Valero, M.; Grillo, I.; Dreiss, C. A. Rupture of Pluronic Micelles by Di-Methylated β-Cyclodextrin Is Not Due to Polypseudorotaxane Formation . J. Phys. Chem. B 2012 , 116 , 1273 - 1281 ). These results combined together give new insights into the mechanisms of protection of the drugs against CD-induced micellar breakup. The outcomes are practical guidelines to improve the design of drug delivery systems

  16. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer.

    Science.gov (United States)

    Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D; Aneja, Ritu

    2015-06-01

    Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of 'most-active fraction' or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate phytochemical synergy among the constituents of Graviola leaf extract (GLE) compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions. Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced bioavailability of rutin in FEF compared to GLE. However, GLE was more effective in inhibiting in vitro prostate cancer proliferation, viability and clonogenic capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold higher tumor growth-inhibitory efficacy than FEF in human prostate tumor xenografts although the concentration of rutin and Q-3-G was more in FEF. Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity. Our data indicate that despite lower absorption and bioavailability of rutin, maximum efficacy was achieved in the case of GLE, which also comprises of other phytochemical groups including acetogenins that make up its natural complex environment. Hence, our study emphasizes on evaluating the nature of interactions among Graviola leaf phytochemcials for developing favorable dose regimen for prostate cancer management to achieve optimal therapeutic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions

  17. Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

    2017-05-01

    Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

  18. Speed of flea knockdown of spinosad compared to afoxolaner, and of spinosad through 28 days post-treatment in controlled laboratory studies.

    Science.gov (United States)

    Snyder, Daniel E; Rumschlag, Anthony J; Young, Lisa Marie; Ryan, William G

    2015-11-09

    The speed of flea knockdown by different products and their duration of effectiveness are factors which affect veterinarian prescribing decisions. To further validate the month-long pulicidal effectiveness of spinosad and determine its rate of flea knockdown to that of afoxolaner, three studies were conducted in two laboratories in the United States, utilizing flea infestations from colonies which are regularly refreshed through introduction of locally caught fleas. All study assessors were blinded, dogs were ranked by pre-study flea counts and randomized accordingly, and treatments administered on Day 0. All studies included a negative control group; two also included an afoxolaner group. In one study, flea challenges for treated and control dogs (10 per group) were completed 21 and 28 days after treatment and counts were performed 24 h later. In each of two speed-of-knockdown (SOK) studies, 36 dogs were randomized, six dogs per group, to: untreated controls; administered oral afoxolaner (2.6-6.2 mg/kg); or oral spinosad (32.1-59.2 mg/kg). In the SOK studies, live fleas from Day -1 infestations were counted after being combed off at 1 and 3 h after treatment, and after reinfestations on Day 7. There were no treatment-related adverse events. Spinosad was 98.6% effective at 28 days post treatment. For SOK, geometric mean live flea counts for afoxolaner were not different from controls at any assessment. For spinosad, all mean counts were significantly lower than in controls (p ≤ 0.0128) except at 1 h post treatment in both studies. Spinosad was significantly more effective than afoxolaner in both studies at 3 h post treatment (p ≤ 0.0065) and post-Day 7 infestation (p ≤ 0.0054), and at 1 h post treatment (p = 0.0276) and post-Day 7 infestation in one study. These data validate spinosad's faster onset of flea knockdown than afoxolaner against infestations present at the time of treatment, and faster residual speed of flea knockdown for at least

  19. Work stress, worries, and pain interact synergistically with modelled traffic noise on cross-sectional associations with self-reported sleep problems

    OpenAIRE

    Kristiansen, Jesper; Persson, Roger; Björk, Jonas; Albin, Maria; Jakobsson, Kristina; Östergren, Per-Olof; Ardö, Jonas

    2011-01-01

    To examine the risk of sleep problems associated with work stress (job strain, job demands, and decision authority), worries and pain and to investigate the synergistic interaction between these factors and traffic noise. Sleep problems and predictor variables were assessed in a cross-sectional public health survey with 12,093 respondents. Traffic noise levels were assessed using modelled A-weighted energy equivalent traffic sound levels at the residence. The risk of sleep problems was modell...

  20. Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.

    Science.gov (United States)

    Dasmahapatra, Girija; Lembersky, Dmitry; Rahmani, Mohamed; Kramer, Lora; Friedberg, Jonathan; Fisher, Richard I; Dent, Paul; Grant, Steven

    2009-05-01

    Mechanisms underlying interactions between the proteasome inhibitor bortezomib and small molecule Bcl-2 antagonists were examined in GC- and ABC-type human DLBCL (diffuse lymphocytic B-cell lymphoma) cells. Concomitant or sequential exposure to non- or minimally toxic concentrations of bortezomib or other proteasome inhibitors and either HA14-1 or gossypol resulted in a striking increase in Bax/Bak conformational change/translocation, cytochrome c release, caspase activation and synergistic induction of apoptosis in both GC- and ABC-type cells. These events were associated with a sharp increase in activation of the stress kinase JNK and evidence of ER stress induction (e.g., eIF2alpha phosphorylation, activation of caspases-2 and -4, and Grp78 upregulation). Pharmacologic or genetic (e.g., shRNA knockdown) interruption of JNK signaling attenuated HA14-1/bortezomib lethality and ER stress induction. Genetic disruption of the ER stress pathway (e.g., in cells expressing caspase-4 shRNA or DN-eIF2alpha) significantly attenuated lethality. The toxicity of this regimen was independent of ROS generation. Finally, HA14-1 significantly increased bortezomib-mediated JNK activation, ER stress induction, and lethality in bortezomib-resistant cells. Collectively these findings indicate that small molecule Bcl-2 antagonists promote bortezomib-mediated mitochondrial injury and lethality in DLBCL cells in association with enhanced JNK activation and ER stress induction. They also raise the possibility that such a strategy may be effective in different DLBCL sub-types (e.g., GC- or ABC), and in bortezomib-resistant disease.

  1. Synergistic interactions between the NS3(hel and E proteins contribute to the virulence of dengue virus type 1.

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    Luana de Borba

    Full Text Available BACKGROUND: Dengue includes a broad range of symptoms, ranging from fever to hemorrhagic fever and may occasionally have alternative clinical presentations. Many possible viral genetic determinants of the intrinsic virulence of dengue virus (DENV in the host have been identified, but no conclusive evidence of a correlation between viral genotype and virus transmissibility and pathogenicity has been obtained. METHODOLOGY/PRINCIPAL FINDINGS: We used reverse genetics techniques to engineer DENV-1 viruses with subsets of mutations found in two different neuroadapted derivatives. The mutations were inserted into an infectious clone of DENV-1 not adapted to mice. The replication and viral production capacity of the recombinant viruses were assessed in vitro and in vivo. The results demonstrated that paired mutations in the envelope protein (E and in the helicase domain of the NS3 (NS3(hel protein had a synergistic effect enhancing viral fitness in human and mosquito derived cell lines. E mutations alone generated no detectable virulence in the mouse model; however, the combination of these mutations with NS3(hel mutations, which were mildly virulent on their own, resulted in a highly neurovirulent phenotype. CONCLUSIONS/SIGNIFICANCE: The generation of recombinant viruses carrying specific E and NS3(hel proteins mutations increased viral fitness both in vitro and in vivo by increasing RNA synthesis and viral load (these changes being positively correlated with central nervous system damage, the strength of the immune response and animal mortality. The introduction of only pairs of amino acid substitutions into the genome of a non-mouse adapted DENV-1 strain was sufficient to alter viral fitness substantially. Given current limitations to our understanding of the molecular basis of dengue neuropathogenesis, these results could contribute to the development of attenuated strains for use in vaccinations and provide insights into virus/host interactions

  2. Fitness Trade-Off Associated With Spinosad Resistance in Frankliniella occidentalis (Thysanoptera: Thripidae).

    Science.gov (United States)

    Li, Xiaoyu; Wan, Yanran; Yuan, Guangdi; Hussain, Sabir; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wu, Qingjun

    2017-08-01

    Frankliniella occidentalis (Pergande) is an economically important pest of agricultural crops. High resistance has been detected in field populations of F. occidentalis against the insecticide spinosad. In this study, we compared life history traits, body sizes, and feeding behaviors (recorded via an electrical penetration graph) of spinosad-susceptible (Ivf03) and spinosad-resistant (NIL-R) near-isogenic lines of F. occidentalis. Life table analysis showed that NIL-R had reduced female longevity and reduced fecundity. The relative fitness of NIL-R (0.43) was less than half that of Ivf03. NIL-R individuals were smaller than Ivf03 individuals, both in body length and body width at every stage. The number and duration of feeding activities were significantly reduced in NIL-R, with the exception of total duration of long-ingestion probes. These results suggest that there is a fitness trade-off associated with spinosad resistance in F. occidentalis, and that the development of resistance in this pest species may be reduced by rotating spinosad with other pesticides lacking cross-resistance. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Spinosad: a biorational mosquito larvicide for use in car tires in southern Mexico

    Directory of Open Access Journals (Sweden)

    Marina Carlos F

    2012-05-01

    Full Text Available Abstract Background Car tires are important habitats for mosquito development because of the high density populations they can harbor and their presence in urban settings. Water in experimental tires was treated with one of three insecticides or an untreated control. Aquatic invertebrates were sampled at weekly intervals. Eggs, larval and pupal samples were laboratory-reared to estimate seasonal fluctuations in Aedes aegypti and Ae. albopictus abundance. Results Spinosad treatments at 1 or 5 ppm (mg a.i./liter provided 6–8 weeks of effective control of Ae. aegypti, Ae. albopictus, Culex quinquefasiatus and Cx. coronator larvae, both in the dry season and the rainy season when mosquito populations increased markedly in southern Mexico. Spinosad continued to provide partial control of larvae for several weeks after initial recolonization of treated tires. The larvicidal performance of VectoBac 12AS (Bacillus thuringiensis var. israelensis was relatively poor with one week of complete control of Aedes spp. larvae and no discernible control of Culex spp., whereas the duration of larvicidal activity of 1% temephos mineral-based granules was intermediate between those of VectoBac and spinosad treatments. Populations of chironomids, ostracods and Toxorhynchites theobaldi were generally reduced in spinosad and temephos treatments, but were similar in control and VectoBac treatments. Conclusion The present study is the first to report spinosad as an effective larvicide against Cx. coronator, which is currently invading the southern United States. These results substantiate the use of spinosad as a highly effective mosquito larvicide, even in habitats such as unused car tires that can represent prolific sources of adult mosquitoes.

  4. Spinosad and the Tomato Borer Tuta absoluta: A Bioinsecticide, an Invasive Pest Threat, and High Insecticide Resistance

    Science.gov (United States)

    Campos, Mateus R.; Rodrigues, Agna Rita S.; Silva, Wellington M.; Silva, Tadeu Barbosa M.; Silva, Vitória Regina F.; Guedes, Raul Narciso C.; Siqueira, Herbert Alvaro A.

    2014-01-01

    The introduction of an agricultural pest species into a new environment is a potential threat to agroecosystems of the invaded area. The phytosanitary concern is even greater if the introduced pest’s phenotype expresses traits that will impair the management of that species. The invasive tomato borer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is one such species and the characterization of the insecticide resistance prevailing in the area of origin is important to guide management efforts in new areas of introduction. The spinosad is one the main insecticides currently used in Brazil for control of the tomato borer; Brazil is the likely source of the introduction of the tomato borer into Europe. For this reason, spinosad resistance in Brazilian populations of this species was characterized. Spinosad resistance has been reported in Brazilian field populations of this pest species, and one resistant population that was used in this study was subjected to an additional seven generations of selection for spinosad resistance reaching levels over 180,000-fold. Inheritance studies indicated that spinosad resistance is monogenic, incompletely recessive and autosomal with high heritability (h 2 = 0.71). Spinosad resistance was unstable without selection pressure with a negative rate of change in the resistance level ( = −0.51) indicating an associated adaptive cost. Esterases and cytochrome P450-dependent monooxygenases titration decreased with spinosad selection, indicating that these detoxification enzymes are not the underlying resistance mechanism. Furthermore, the cross-resistance spectrum was restricted to the insecticide spinetoram, another spinosyn, suggesting that altered target site may be the mechanism involved. Therefore, the suspension of spinosyn use against the tomato borer would be a useful component in spinosad resistance management for this species. Spinosad use against this species in introduced areas should be carefully monitored to

  5. Spinosad and the tomato borer Tuta absoluta: a bioinsecticide, an invasive pest threat, and high insecticide resistance.

    Science.gov (United States)

    Campos, Mateus R; Rodrigues, Agna Rita S; Silva, Wellington M; Silva, Tadeu Barbosa M; Silva, Vitória Regina F; Guedes, Raul Narciso C; Siqueira, Herbert Alvaro A

    2014-01-01

    The introduction of an agricultural pest species into a new environment is a potential threat to agroecosystems of the invaded area. The phytosanitary concern is even greater if the introduced pest's phenotype expresses traits that will impair the management of that species. The invasive tomato borer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is one such species and the characterization of the insecticide resistance prevailing in the area of origin is important to guide management efforts in new areas of introduction. The spinosad is one the main insecticides currently used in Brazil for control of the tomato borer; Brazil is the likely source of the introduction of the tomato borer into Europe. For this reason, spinosad resistance in Brazilian populations of this species was characterized. Spinosad resistance has been reported in Brazilian field populations of this pest species, and one resistant population that was used in this study was subjected to an additional seven generations of selection for spinosad resistance reaching levels over 180,000-fold. Inheritance studies indicated that spinosad resistance is monogenic, incompletely recessive and autosomal with high heritability (h(2) = 0.71). Spinosad resistance was unstable without selection pressure with a negative rate of change in the resistance level ( = -0.51) indicating an associated adaptive cost. Esterases and cytochrome P450-dependent monooxygenases titration decreased with spinosad selection, indicating that these detoxification enzymes are not the underlying resistance mechanism. Furthermore, the cross-resistance spectrum was restricted to the insecticide spinetoram, another spinosyn, suggesting that altered target site may be the mechanism involved. Therefore, the suspension of spinosyn use against the tomato borer would be a useful component in spinosad resistance management for this species. Spinosad use against this species in introduced areas should be carefully monitored to

  6. Evaluation of released malathion and spinosad from chitosan/alginate/gelatin capsules against Culex pipiens larvae

    Directory of Open Access Journals (Sweden)

    Badawy MEI

    2016-09-01

    Full Text Available Mohamed EI Badawy,1 Nehad EM Taktak,2 Osama M Awad,2 Souraya A Elfiki,2 Nadia E Abou El-Ela2 1Department of Pesticide Chemistry and Technology, Faculty of Agriculture, 2Department of Tropical Health, High Institute of Public Health, Alexandria University, Alexandria, Egypt Abstract: Efficacy of spinosad and malathion loaded in eco-friendly biodegradable formulations was evaluated for controlling Culex pipiens larvae. Malathion (organophosphorus larvicide and spinosad (naturally derived insecticide were loaded on chitosan/alginate/gelatin capsules. Capsules were characterized by size measurement, scanning electron microscopy, Fourier transform infrared spectroscopy, and water uptake. In vitro release kinetics of the larvicides was studied in the running and stagnant water. Biochemical studies on the larvae treated with technical and formulated insecticides were also demonstrated. The results indicated that the released spinosad was active for a long time up to 48 and 211 days in the running and stagnant water, respectively. However, the capsules loaded with malathion showed larvicidal activity for 20 and 27 days in the running and stagnant water, respectively. Technical and formulated malathion and spinosad had an inhibition effect on acetylcholinesterase, carboxylesterase, and glutathione S-transferase. The results proved that the prepared capsules consisting of biodegradable polymers containing larvicides could be effective as controlled-release formulation against C. pipiens larvae for a long period. Keywords: chitosan capsules, larvicide, controlled-release formulation, swelling, mosquitocidal activity, Culex pipiens, biochemical study

  7. Metabolomics analysis of the effect of dissolved oxygen on spinosad production by Saccharopolyspora spinosa.

    Science.gov (United States)

    Lu, Chunzhe; Yin, Jing; Zhao, Fanglong; Li, Feng; Lu, Wenyu

    2017-05-01

    Spinosad, a universal bio-pesticide, is obtained from the soil actinomycete Saccharopolyspora spinosa. Dissolved oxygen, an important contributing factor in aerobic microbial fermentation, however, is not always available in sufficient amounts. To alleviate oxygen limitation in spinosad production, three different oxygen vectors, namely oleic acid, toluene, and n-dodecane, were added into early fermentation. Results indicated that n-dodecane was the optimal oxygen vector. Spinosad yield was increased by 44.2% compared to that in the control group in the presence of 0.5% n-dodecane, added after 120 h of incubation. Yields of the test group reached 6.52 mg/g dry cell weight (DCW), while that of the control group was limited to 4.52 mg/g DCW. Metabolomics analysis by gas chromatography coupled to mass spectrometry was performed to demonstrate the metabolism mechanism in the presence and absence of oxygen vector. In total, 78 principal intracellular metabolites in S. spinosa were detected and quantified in the presence and absence of n-dodecane. Levels of some metabolites that were related to the tricarboxylic acid cycle and pentose phosphate pathway varied significantly. Aspartic acid and glucose-1-phosphate levels varied significantly and contributed most in the distinction of the fermentation conditions and phases. The above findings give new insights into the improvement and the metabolomic characteristics of industrial spinosad production.

  8. 76 FR 12563 - Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime

    Science.gov (United States)

    2011-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No... Elanco Animal Health. The NADA provides for veterinary prescription use of chewable tablets containing spinosad and milbemycin oxime in dogs for the treatment and prevention of flea infestations and for the...

  9. Impact of climate change on filarial vector, Culex quinquefasciatus and control using bacterial pesticide, spinosad

    Directory of Open Access Journals (Sweden)

    Nareshkumar Arjunan

    2014-02-01

    Full Text Available Objective: To show the effect of temperature on the biology of Culex quinquefasciatus and also to show the effect of the bacterial pesticide, spinosad on developmental stages of the filarial vector. Methods: A laboratory colony of mosquito larvae was used for the larvicidal activity of temperature and spinosad. Twenty-five numbers of first, second, third, fourth instar larvae were introduced into the 500 mL glass beaker containing 250 mL of de-chlorinated water with desired temperatures (16 °C, 20 °C, 24 °C, 28 °C, 32 °C, 36 °C, similarly spinosad, at different concentrations. The development was observed for every 24 h. Results: The results showed that the rise in temperature acts as a growth inhibiting factor for mosquitoes. And no development was found in the temperature below 16 °C and above 36 °C. The hatchability was increased as the temperature was increased up to 32 °C, after which eclosion rates dropped gradually. Conclusions: 32 °C was obtained as the maximum sustainable temperature and after which the developmental rate was gradually reduced. The optimal temperature for development was lower than the temperatures at which development was quickest. The bacterial pesticide spinosad showed that it is an effective mosquito control agent and can be used for further integrated pest management programmes.

  10. Evaluation of spinosad for the oral treatment and control of flea infestations on dogs in Europe.

    Science.gov (United States)

    Wolken, S; Franc, M; Bouhsira, E; Wiseman, S; Hayes, B; Schnitzler, B; Jacobs, D E

    2012-01-01

    The novel ectoparasiticide spinosad is a naturally occurring mixture of spinosyns A and D formed during a fermentation process. The spinosyns are tetracyclic macrolides with a unique ring system. Their mode of action differs from that of other commercially available insecticides. Laboratory and field trials were conducted to evaluate the use of spinosad in a chewable tablet at a dose range of 45 to 70 mg/kg for the treatment and control of flea infestations on dogs in Europe. Laboratory studies with artificially infested dogs confirmed persistent activity against Ctenocephalides felis of higher than 99 per cent at three weeks post-treatment with values of 96.5 to 97.8 per cent at four weeks. Two multicentric field trials with naturally infected client-owned animals in five European countries used selamectin as comparator. Monthly doses were given during the summer when many homes were heavily infested. Households with spinosad-treated dogs showed cumulative benefits with flea burdens reduced by about 97 per cent at 14 and 30 days and by 99.6 per cent at 60 and 90 days. Corresponding figures for selamectin were significantly lower (P<0.05) at all time points: between 88.5 and 91 per cent at 14 and 30 days, then 97.8 and 98.2 per cent at 60 and 90 days. Thus, the performance of spinosad compared favourably with that of the established reference product.

  11. Origin of selenium–gold interaction in F2CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH3): Synergistic effects

    International Nuclear Information System (INIS)

    Guo, Xin; Yang, Yu-Ping; Li, Qing-Zhong; Li, Hai-Bei

    2016-01-01

    Selenium–gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium–gold interaction by studying complexes F 2 CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH 3 ). The results showed that the formation of selenium–gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au—Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium–gold interaction. Interestingly, the chalcogen–gold interaction becomes stronger with the increase of chalcogen atomic mass in F 2 CX⋯AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH 3 into F 2 CSe⋯AuY, in which selenium–gold interaction is weakened and selenium–nitrogen interaction is strengthened due to the synergistic effects.

  12. Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

    Science.gov (United States)

    Prasad, Dev; Chauhan, Harsh; Atef, Eman

    2014-11-01

    The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. Toxic effect and biochemical study of chlorfluazuron, oxymatrine, and spinosad on honey bees (Apis mellifera).

    Science.gov (United States)

    Rabea, Entsar I; Nasr, Hoda M; Badawy, Mohamed E I

    2010-04-01

    Under laboratory conditions, the comparative effects of two insect growth regulators, chlorfluazuron and oxymatrine, and spinosad as a biopesticide were examined on honey bee workers (Apis mellifera L.). Separate groups of bees were left for 24 h to feed on 50% sucrose solution containing different concentrations of the tested insecticides, and the lethal concentration that caused 50% mortality (LC(50)) was estimated. The inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities as biochemical indicators were determined in vivo after 24 h in head, thorax, and abdomen of surviving bees obtained after treatments with a view to explore the possible mode of action of these compounds. Results indicated that exposure to spinosad showed toxicity to honey bees with LC(50) value of 7.34 mg L(-1), followed by oxymatrine (LC(50) = 10.68 mg L(-1)), while chlorfluazuron was the least acutely toxic of the tested compounds (LC(50) = 2,526 mg L(-1)). Oxymatrine and spinosad at the same tested concentrations (2.5, 5, 10, and 20 mg L(-1)) significantly inhibited AChE activity in different organs of honey bee workers, and high inhibition percentage was obtained with the enzyme isolated from the thorax. However, chlorfluazuron at 400, 1,000, 2,000, and 4,000 mg L(-1) caused high inhibition of AChE activity isolated from the head (39.65% and 44.22% at 2,000 and 4,000 mg L(-1), respectively). In addition, the toxic effects of the tested compounds on activity of ATPase indicated that spinosad caused the highest inhibitory effect in different organs compared with oxymatrine at the same concentrations, and high inhibition was found with ATPase isolated from the head. The results also indicated that oxymatrine was the least active compound for inhibition of AChE and ATPase.

  14. Perfectly Wetting Mixtures of Surfactants from Renewable Resources: The Interaction and Synergistic Effects on Adsorption and Micellization.

    Science.gov (United States)

    Szumała, Patrycja; Mówińska, Alicja

    This paper presents a study of the surface properties of mixtures of surfactants originating from renewable sources, i.e., alkylpolyglucoside (APG), ethoxylated fatty alcohol (AE), and sodium soap (Na soap). The main objective was to optimize the surfactant ratio which produces the highest wetting properties during the analysis of the solution of the individual surfactants, two- and three-component mixtures, and at different pH values. The results showed the existence of a synergistic effect in lowering the interfacial tension, critical micelle concentration and the formation of mixed micelles in selected solutions. We found that best wetting properties were measured for the binary AE:APG mixtures. It has been demonstrated that slightly lower contact angles values were observed on Teflon and glass surfaces for the AE:APG:soap mixtures but the results were obtained for higher concentration of the components. In addition, all studied solutions have very good surface properties in acidic, basic and neural media. However, the AE:soap (molar ratio of 1:2), AE:APG (2:1) and AE:APG:soap (1:1:1) compositions improved their wetting power at pH 7 on the aluminium and glass surfaces, as compared to solutions at other pH values tested (selected Θ values close to zero-perfectly wetting liquids). All described effects detected would allow less surfactant to be used to achieve the maximum capacity of washing, wetting or solubilizing while minimizing costs and demonstrating environmental care.

  15. Hepato- and nephrotoxicity in male albino rats exposed to malathion and spinosad in stored wheat grains.

    Science.gov (United States)

    Zidan, Nour El-Hoda A

    2015-06-01

    Adult male albino rats were fed on stored wheat grains (Triticum aestivum L.) treated with malathion and spinosad at both 8 and 16 ppm for 90 consecutive days to evaluate their hepatic and renal toxicity. The activity of serum acetylcholinesterase (AChE) was decreased in rats treated with the higher concentration of both tested pesticides. Biochemical parameters of liver functions [i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), acid phosphatase (ACP) activity, as well as total protein, albumin, bilirubin and cholesterol levels] were severely affected especially at higher concentration. Malathion and spinosad elevated the activity of ALT, AST, ALP and ACP in rats treated with the higher concentration. Also, total and direct bilirubin levels increased in rats treated with the higher concentration of both pesticides. On the contrary, both pesticides decreased total protein and albumin levels in treated rats in a concentration-dependent manner. Furthermore, malathion was found to be hyperglycemic. Kidney function parameters (i.e., urea and creatinine levels) were increased in treated rats in a concentration-dependent manner. The above mentioned effects were supported by histopathological examination of liver and kidney tissues. The obtained results indicated also that malathion was able to cause a more pronounced hepato- and renal toxicity in rats than spinosad.

  16. Physiological response of a spinosad-producing strain saccharopolyspora spinosa to space flight

    Science.gov (United States)

    Liu, Zhiheng

    This study explored the physiological response of spinosad-producing strain Saccharopolyspora spinosa to space flight environment. The production strain was carried into space by a manned spaceship, `Shenzhou VII' (Divine Vessel VII) and compared with identical ground control strains. The results showed that space flight could induce a significant response in the phys-iological characteristics of S. spinosa, including change of productivity and morphology. The spinosad yield of the mutants increased more than 95% comparing to the original strains. And in the mutant library, a peculiar morphologic strain, F-200, was found. F-200 produced no spinosad, and was much larger than normal ones and spores were lilac, while the others remain white. During fermentation, the color of the entire broth of F-200 had completely changed to purple, whereas the broth of the ground control Zu8 remained yellow. The results demonstrated that the space flight can induce physiological changes of S. spinosa and could potentially serve as mutagenesis tools to improve commercial-significant microbial metabolites.

  17. Demonstration of an adaptive response to preconditioning Frankliniella occidentalis (Pergande) to sublethal doses of spinosad: a hormetic-dose response.

    Science.gov (United States)

    Gong, Youhui; Xu, Baoyun; Zhang, Youjun; Gao, Xiwu; Wu, Qingjun

    2015-07-01

    Sublethal doses of some insecticides have been reported to either stimulate or reduce the survival and fecundity of insects. Many sublethal-effect studies have been conducted after exposure of only one generation to sublethal insecticides, and there is little information about the sublethal effects on insects after long-term exposure to sublethal insecticides. In this study, changes in biological characteristics were investigated in spinosad-susceptible (Spin-S) and sublethal-spinosad-treated (Spin-Sub) strains of Frankliniella occidentalis (Pergande) after exposure to their corresponding sublethal concentrations of spinosad. The results showed that for the Spin-S strain, the LC10 concentration of spinosad slightly affected the biotic fitness both in parents and offspring of F. occidentalis. The LC25 concentration of spinosad prolonged the development time, reduced the fecundity, and significantly reduced the intrinsic rate of increase, the net reproductive rate and the finite rate of increase in the Spin-S strain. However, the negative effects were not as pronounced in the offspring (F1 generation) as in the parent generation. For the Spin-Sub strain, the LC10 and LC25 concentrations of spinosad had little negative effect on the development and fecundity, and no significant difference was found between the effects of the LC10 and LC25 treatments on the Spin-Sub strain. The Spin-Sub strain exhibited a shorter developmental time, and larger intrinsic rates of increase and net reproductive rates, compared with the corresponding treatments of the Spin-S strain. These findings combined with our previous studies suggest that the biotic fitness increased in the Spin-Sub strain and the strain became more adaptable to sublethal doses of spinosad, compared with the Spin-S strain. Physiological and biochemical adaptation may contribute to these changes after long treatment times at sublethal doses.

  18. Heat shock protein 47 and 65-kDa FK506-binding protein weakly but synergistically interact during collagen folding in the endoplasmic reticulum.

    Science.gov (United States)

    Ishikawa, Yoshihiro; Holden, Paul; Bächinger, Hans Peter

    2017-10-20

    Collagen is the most abundant protein in the extracellular matrix in humans and is critical to the integrity and function of many musculoskeletal tissues. A molecular ensemble comprising more than 20 molecules is involved in collagen biosynthesis in the rough endoplasmic reticulum. Two proteins, heat shock protein 47 (Hsp47/ SERPINH1 ) and 65-kDa FK506-binding protein (FKBP65/ FKBP10 ), have been shown to play important roles in this ensemble. In humans, autosomal recessive mutations in both genes cause similar osteogenesis imperfecta phenotypes. Whereas it has been proposed that Hsp47 and FKBP65 interact in the rough endoplasmic reticulum, there is neither clear evidence for this interaction nor any data regarding their binding affinities for each other. In this study using purified endogenous proteins, we examined the interaction between Hsp47, FKBP65, and collagen and also determined their binding affinities and functions in vitro Hsp47 and FKBP65 show a direct but weak interaction, and FKBP65 prefers to interact with Hsp47 rather than type I collagen. Our results suggest that a weak interaction between Hsp47 and FKBP65 confers mutual molecular stability and also allows for a synergistic effect during collagen folding. We also propose that Hsp47 likely acts as a hub molecule during collagen folding and secretion by directing other molecules to reach their target sites on collagens. Our findings may explain why osteogenesis imperfecta-causing mutations in both genes result in similar phenotypes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Synergistic Interaction between Metformin and Sulfonylureas on Diclofenac-Induced Antinociception Measured Using the Formalin Test in Rats

    Directory of Open Access Journals (Sweden)

    Mario I Ortiz

    2013-01-01

    Full Text Available BACKGROUND: There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA.

  20. Synergistic effect of receptor-interacting protein 140 and simvastatin on the inhibition of proliferation and survival of hepatocellular carcinoma cells.

    Science.gov (United States)

    Xia, Kun; Zhang, Panpan; Hu, Jian; Hou, Huan; Xiong, Mingdi; Xiong, Junping; Yan, Nianlong

    2018-04-01

    Hepatocellular carcinoma is the sixth most prevalent malignant tumor and the third most common cause of cancer-associated mortality. Statins have been investigated for carcinoma prevention and treatment. In addition, receptor-interacting protein 140 (RIP140) has been observed to inhibit the Wnt/β-catenin signaling pathway and cell growth. The present study aimed to investigate whether simvastatin (SV) is able to induce SMCC-7721 cell apoptosis through the Wnt/β-catenin signaling pathway. Initially, a cell model of RIP140 overexpression was established, and then cells were treated with SV. The cell growth, viability and apoptosis were measured by cell counting kit-8 and flow cytometry. Furthermore, the expression levels of RIP140, β-catenin, c-myc and cyclin D1 were detected by reverse transcription-quantitative polymerase chain, western blot analysis and immunofluorescence. The results demonstrated that SV significantly increased the expression of RIP140 in SMCC-7721 cells; however, β-catenin, c-myc and cyclin D1 levels were significantly decreased. Furthermore, the immunofluorescence assay of β-catenin confirmed that SV decreased the content of this protein in SMCC-7721 cells. Notably, RIP140 exerted a synergistic effect on the apoptosis rate induced by SV (RIP140 + SV group), while the alteration in RIP140, β-catenin, c-myc and cyclin D1 levels was more evident in the combination group as compared with the RIP140 or SV alone groups. In conclusion, these results suggested that SV is able to induce the apoptosis of SMCC-7721 cells through the Wnt/β-catenin signaling pathway, as well as that RIP140 and SV exert a synergistic effect on the inhibition of cell proliferation and survival.

  1. Mussel byssus-inspired engineering of synergistic nanointerfacial interactions as sacrificial bonds into carbon nanotube-reinforced soy protein/nanofibrillated cellulose nanocomposites: Versatile mechanical enhancement

    Science.gov (United States)

    Wang, Zhong; Zhao, Shujun; Kang, Haijiao; Zhang, Wei; Zhang, Shifeng; Li, Jianzhang

    2018-03-01

    Achieving flexible and stretchable biobased nanocomposites combining high strength and toughness is still a very challenging endeavor. Herein, we described a novel and versatile biomimetic design for tough and high-performance TEMPO-oxidized nanofibrillated cellulose (TONFC)/soy protein isolate (SPI) nanocomposites, which are triggered by catechol-mimetic carbon nanotubes (PCT) and iron ions (Fe(III)) to yield a strong yet sacrificial metal-ligand motifs into a chemically cross-linked architecture network. Taking advantage of self-polymerization of catechol-inspired natural tannic acid, PCT nanohybrid was prepared through adhering reactive poly-(tannic acid) (PTA) layer onto surfaces of carbon nanotubes via a simple dip-coating process. The high-functionality PCT induced the formation of the metal-ligand bonds through the ionic coordinates between the catechol groups in PCT and -COOH groups of TONFC skeleton with Fe(III) mediation that mimicked mussel byssus. Upon stretching, this tailored TONFC-Fe(III)-catechol coordination bonds served as sacrificial bonds that preferentially detach prior to the covalent network, which gave rise to efficient energy dissipation that the nanocomposites integrity was survived. As a result of these kind of synergistic interfacial interactions (sacrificial and covalent bonding), the optimal nanocomposite films processed high tensile strength (ca. 11.5 MPa), large elongation (ca. 79.3%), remarkable toughness (ca. 6.9 MJ m-3), and favorable water resistance as well as electrical conductivity. The proposed bioinspired strategy for designing plant protein-based materials enables control over their mechanical performance through the synergistic engineering of sacrificial bonds into the composite interface.

  2. A nicotinic acetylcholine receptor transmembrane point mutation (G275E) associated with resistance to spinosad in Frankliniella occidentalis.

    Science.gov (United States)

    Puinean, Alin M; Lansdell, Stuart J; Collins, Toby; Bielza, Pablo; Millar, Neil S

    2013-03-01

    High levels of resistance to spinosad, a macrocyclic lactone insecticide, have been reported previously in western flower thrips, Frankliniella occidentalis, an economically important insect pest of vegetables, fruit and ornamental crops. We have cloned the nicotinic acetylcholine receptor (nAChR) α6 subunit from F. occidentalis (Foα6) and compared the nucleotide sequence of Foα6 from susceptible and spinosad-resistant insect populations (MLFOM and R1S respectively). A single nucleotide change has been identified in Foα6, resulting in the replacement of a glycine (G) residue in susceptible insects with a glutamic acid (E) in resistant insects. The resistance-associated mutation (G275E) is predicted to lie at the top of the third α-helical transmembrane domain of Foα6. Although there is no direct evidence identifying the location of the spinosad binding site, the analogous amino acid in the C. elegans glutamate-gated chloride channel lies in close proximity (4.4 Å) to the known binding site of ivermectin, another macrocyclic lactone pesticide. The functional consequences of the resistance-associated mutation have been examined in the human nAChR α7 subunit. Introduction of an analogous (A272E) mutation in α7 abolishes the modulatory effects of spinosad whilst having no significant effect upon activation by acetylcholine, consistent with spinosad having an allosteric mechanism of action. © 2012 International Society for Neurochemistry.

  3. Performance of pre-commercial release formulations of spinosad against five stored-product insect species on four stored commodities.

    Science.gov (United States)

    Subramanyam, Bhadriraju; Hartzer, Michelle; Boina, Dhana Raj

    2012-09-01

    Two liquid and one dry pre-commercial release spinosad formulations were evaluated at the labeled rate of 1 ppm against five stored-grain insect species on wheat, short-grain rice, long-grain rice, and maize. Except on maize, efficacy of spinosad was compared with a currently registered grain protectant, chlorpyrifos-methyl (3 ppm) plus deltamethrin (0.5 ppm). The 7- and 14-day mortalities of the lesser grain borer, Rhyzopertha dominica, were 99.0-100.0% on spinosad and chlorpyrifos-methyl plus deltamethrin-treated wheat, short-grain rice, and long-grain rice. Adult progeny of R. dominica after 42 days on these commodities decreased by 99.7-100.0% relative to progeny production on untreated wheat. Mortality and reduction in adult progeny of the rice weevil, Sitophilus oryzae, on the three commodities, and that of the maize weevil, Sitophilus zeamais, on maize and the red flour beetle, Tribolium castaneum, on wheat were 100.0% only with chlorpyrifos-methyl plus deltamethrin. The liquid spinosad formulations were most effective against the Indianmeal moth, Plodia interpunctella, on maize and wheat. Except for R. dominica, the effectiveness of spinosad on the other species varied with the formulation, exposure time, and commodity. Chlorpyrifos-methyl plus deltamethrin was effective against insect species on the commodities tested.

  4. Analysis of differentially expressed genes related to resistance in spinosad- and neonicotinoid-resistant Musca domestica L. (Diptera: Muscidae) strains

    DEFF Research Database (Denmark)

    Castberg, Dorte Heidi Højland; Kristensen, Michael

    2017-01-01

    interesting in terms of neonicotinoid resistance, while cyp4d9 was overexpressed in 791spin compared to spinosad-susceptible strains. GSTs, ESTs and UGTs were mostly overexpressed, but not to the same degree as P450s. We present a comprehensive and comparative picture of gene expression in three housefly......Background The housefly is a global pest that has developed resistance to most insecticides applied against it. Resistance of the spinosad-resistant strain 791spin and the neonicotinoid-resistant 766b strain is believed to be due to metabolism. We investigate differentially expressed genes...... strains differing significantly in their response to insecticides. High differential expression of P450s and genes coding for cuticle protein indicates a combination of factors involved in metabolic neonicotinoid and spinosad resistance. Conclusion Resistance in these strains is apparently not linked...

  5. Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict

    Directory of Open Access Journals (Sweden)

    Jernigan Katherine

    2010-04-01

    Full Text Available Abstract Background Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD; prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR on liability for ADHD. Method 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution was genotyped and participants were assigned as having high (La/La N = 78, intermediate (La/Lg, La/short, N = 137, or low (Lg/Lg, Lg/short, short/short, N = 89 serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Results Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Conclusion Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to

  6. Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.

    Science.gov (United States)

    Nikolas, Molly; Friderici, Karen; Waldman, Irwin; Jernigan, Katherine; Nigg, Joel T

    2010-04-16

    Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to

  7. Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict

    Science.gov (United States)

    2010-01-01

    Background Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. Method 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Results Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Conclusion Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict

  8. Immediate and delayed mortality of Rhyzopertha dominica (Coleoptera: Bostrichidae) and Sitophilus oryzae (Coleoptera: Curculionidae) adults exposed to spinosad-treated commodities.

    Science.gov (United States)

    Getchell, Anna Iversen; Subramanyam, Bhadriraju

    2008-06-01

    A series of tests was conducted to characterize differences in the mortality of the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), and rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), exposed to three commodities treated with a liquid and dry spinosad formulation. In laboratory bioassays, adults of the two insect species were exposed to untreated wheat, Triticum aestivum L., corn, Zea mays L., and sorghum, Sorghum bicolor (L.) Moench., and to commodities treated with 1 mg (AI)/kg of liquid and dry spinosad formulations. Mortality was assessed from independent samples examined at specific time intervals to determine immediate mortality and after 24 h of recovery on untreated grain at 28 degrees C and 65% RH to determine delayed mortality. Comparison of the time required for 50% (LT50) and 95% (LT95) mortality indicated that R. dominica adults were consistently and significantly more susceptible (died quickly) than S. oryzae adults when exposed to spinosad-treated commodities. In general, the toxicity of liquid and dry spinosad formulations was similar against R. dominica or S. oryzae. The toxicity of spinosad to each species varied slightly among the three commodities, and there were no consistent trends to suggest that spinosad was more effective on one commodity versus another. LT50 values based on immediate mortality for R. dominica on all commodities ranged from 0.45 to 0.74 d; corresponding values based on delayed mortality ranged from 0.04 to 0.23 d, suggesting delayed toxic action of spinosad in R. dominica. LT50 values based on immediate and delayed mortality for S. oryzae on all three commodities treated with the two spinosad formulations were essentially similar and ranged from 2.75 to 4.56 d. LT95 values for R. dominica based on immediate mortality on spinosad-treated commodities ranged from 1.75 to 3.36 d, and those based on delayed mortality ranged from 0.49 to 1.88 d. There were no significant differences in

  9. Synergistic interaction between the novel histone deacetylase inhibitor ST2782 and the proteasome inhibitor bortezomib in platinum-sensitive and resistant ovarian carcinoma cells.

    Science.gov (United States)

    Gatti, Laura; Benedetti, Valentina; De Cesare, Michelandrea; Corna, Elisabetta; Cincinelli, Raffaella; Zaffaroni, Nadia; Zunino, Franco; Perego, Paola

    2012-08-01

    The ability of histone deacetylase inhibitors to modulate the expression of genes relevant for growth or apoptotis regulation supports their interest in combination treatments of resistant tumors. We explored the effect of the combination of the histone deacetylase inhibitor ST2782 and the proteasome inhibitor bortezomib in ovarian carcinoma cell lines, including the IGROV-1 cell line and two p53 mutant platinum-resistant sublines (IGROV-1/OHP and IGROV-1/Pt1). We found a synergistic interaction between the two drugs, more evident in the p53-mutant resistant sublines, which was associated with increa sed apoptosis. The treatment with ST2782 resulted in early induction of Bax as well as in cleavage of caspase 3 and poly (ADP-ribose) polymerase only in the resistant cell lines. The inhibition of p53-transcriptional transactivation by pifithrin alpha in IGROV-1 cells enhanced the synergism. Conversely, knockdown of endogenous wild-type p53 in IGROV-1 cells determined synergism reduction. These opposite effects support the relevance of the transactivation-deficient mutant p53 as a synergism determinant. Moreover, in vivo studies indicated that tumor growth inhibition tended to be more evident in mice receiving the drug combination than in those treated with bortezomib alone. Overall, our study supports the potential effectiveness of the combination in platinum drug-resistant ovarian cancer carrying mutant p53. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Synergistic Interaction of Methanol Extract from Canarium odontophyllum Miq. Leaf in Combination with Oxacillin against Methicillin-Resistant Staphylococcus aureus (MRSA ATCC 33591

    Directory of Open Access Journals (Sweden)

    Dayang Fredalina Basri

    2016-01-01

    Full Text Available Canarium odontophyllum (CO Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5. The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves of C. odontophyllum have the potential to be developed into antistaphylococcal agents.

  11. Synergistic Interaction of Methanol Extract from Canarium odontophyllum Miq. Leaf in Combination with Oxacillin against Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 33591.

    Science.gov (United States)

    Basri, Dayang Fredalina; Sandra, Vimashiinee

    2016-01-01

    Canarium odontophyllum (CO) Miq. has been considered as one of the most sought-after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 μg/mL and 156.25 μg/mL and Minimum Bactericidal Concentration (MBC) of 625 μg/mL and 312.5 μg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract-oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index ≤ 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 × MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves of C. odontophyllum have the potential to be developed into antistaphylococcal agents.

  12. Titania species on two-dimensional HNbMoO6 nanosheets: structural feature, interaction model, and synergistic effect for photocatalytic degradation of methylene blue

    Science.gov (United States)

    Hu, Lifang; He, Jie; Xu, Lei; Li, Dewei; Zhang, Peipei

    2016-10-01

    HNbMoO6-based nanocomposite material T-HNbMoO6 is assembled by titania species dispersed on HNbMoO6 nanosheets (N-HNbMoO6), which is obtained through the mechanical exfoliation of layered HNbMoO6 (L-HNbMoO6). The microstructures, skeleton features, and spectral-response characteristics of the as-prepared materials were characterized by means of technologies, such as powder x-ray diffraction, field emission scanning electron microscope with energy dispersive spectroscopy mapping, high-resolution transmission electron microscopy with energy dispersive x-ray spectrometer, N2 adsorption-desorption isotherms, laser Raman spectroscopy, x-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, Mott-Schottky curves, and H2 temperature-programmed reduction analysis. The photocatalytic activity was evaluated by the degradation of methylene blue dye under the Xe lamp irradiation. The results showed that the titania species are dispersed on the surface of N-HNbMoO6 resulting from the interaction between guest titania species and host N-HNbMoO6. T-HNbMoO6 owns the best photocatalytic performance, which may be attributed to the synergistic effect between N-HNbMoO6 and titania species.

  13. Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

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    Daniela Massihnia

    2017-01-01

    Full Text Available Abstract Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC, associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs with specimens tissue from radically-resected patients (n = 100. Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their Akt1 mRNA and phospho-Akt/Akt levels by quantitative-RT-PCR and immunocytochemistry. Growth inhibitory effects of Akt inhibitors and gemcitabine were evaluated by SRB assay, whereas modulation of Akt and phospho-Akt was investigated by Western blotting and ELISA. Cell cycle perturbation, apoptosis-induction, and anti-migratory behaviors were studied by flow cytometry, AnnexinV, membrane potential, and migration assay, while pharmacological interaction with gemcitabine was determined with combination index (CI method. Results Immunohistochemistry of TMAs revealed a correlation between phospho-Akt expression and worse outcome, particularly in patients with the highest phospho-Akt levels, who had significantly shorter overall and progression-free-survival. Similar expression levels were detected in LPC028 primary cells, while LPC006 were characterized by low phospho-Akt. Remarkably, Akt inhibitors reduced cancer cell growth in monolayers and spheroids and synergistically enhanced the antiproliferative activity of gemcitabine in LPC028, while this combination was antagonistic in LPC006 cells. The synergistic effect was paralleled by a reduced expression of ribonucleotide reductase, potentially facilitating gemcitabine cytotoxicity. Inhibition of Akt

  14. A synergistic interaction between transcription factors nuclear factor-κB and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion

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    Yoon Jiyeon

    2013-02-01

    Full Text Available Abstract Background The transcription factor nuclear factor-κB (NF-κB has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-κB and signal transducers and activators of transcription 3 (STAT3 in controlling metastatic potential of gastric cancer cells. Methods Immunohistochemistry for NF-κB p65 (RelA, phospho-Tyr705-STAT3 (pSTAT3, or matrix metalloproteinase 9 (MMP9 was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-κB inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-κB repressor mutant of IκBα, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. Results NF-κB and STAT3 were constitutively activated and were positively correlated (P = 0.038 in gastric cancer tissue specimens. In cell culture experiments, NF-κB inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-κB activation. Moreover, both NF-κB inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-κB activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P = 0.001 and P = 0.022, respectively, decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. Conclusion NF-κB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-κB and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.

  15. The involvement of DNA repair genes in the hypoxia-dependent NLCQ-1 (NSC 709257) toxicity and its synergistic interaction with cisplatin or melphalan

    International Nuclear Information System (INIS)

    Papadopoulou, M.V.; Xue, C.-J.; Bloomer, W.D.

    2003-01-01

    4-[3-(2-Nitro-1-imidazolyl)-propylamino]-7-chloro-quinoline hydrochloride (NLCQ-1) is a weakly DNA-intercalating hypoxia selective cytotoxin, which synergistically enhances the antitumor effect of several chemotherapeutic agents or radiation against mouse tumors or human xenografts. Synergy with melphalan (L-PAM) or cisplatin (cisPt) requires hypoxic pre-exposure of cells to NLCQ-1 or, in mice, administration of NLCQ-1 about 1 h before L-PAM or cisPt. This suggests that NLCQ-1 may cause DNA lesions upon reductive metabolism. To indirectly identify such lesions, rodent cell lines defective in specific DNA repair genes (EM9 and UV41) and their repair-proficient parental AA8, were exposed to NLCQ-1 alone and in combination with L-PAM or cisPt under hypoxic/aerobic conditions and appropriate routes, and assessed for clonogenicity. Selected comparisons with tirapazamine (TPZ) were also performed. DNA ssbs were identified by using the alkaline comet assay. Synergism was assessed by isobologramic analysis. EM9, which lack the functional XRCC1 gene and are unable to efficiently repair DNA ssbs, were 3.7x and 4.5x more sensitive to NLCQ-1 and TPZ, respectively, than the parental AA8 cells. Similarly, UV41, which are defective in the ERCC4/XPF gene and thus, hypersensitive to DNA cross-linking agents, were 4.1x more sensitive than AA8 cells to NLCQ-1. Equitoxic concentrations of NLCQ-1 and TPZ gave similar numbers of ssbs in AA8 and EM9 cells exposed to each compound for 1 h under hypoxic conditions. In combination with L-PAM or cisPt, synergy was observed in AA8 but not in EM9 or UV41 cells, with either NLCQ-1 or TPZ. These results suggest that NLCQ-1 is involved in the formation of DNA ssbs and interstrand crosslinks, with the latter being most likely responsible for NLCQ-1 hypoxic toxicity. The synergistic interaction of NLCQ-1 with L-PAM or cisPt is probably due to an enhancement in the L-PAM/cisPt-induced DNA interstrand crosslinks, possibly as a result of an inhibited

  16. Synergistic interaction of Rhizobium leguminosarum bv. viciae and arbuscular mycorrhizal fungi as a plant growth promoting biofertilizers for faba bean (Vicia faba L.) in alkaline soil.

    Science.gov (United States)

    Abd-Alla, Mohamed Hemida; El-Enany, Abdel-Wahab Elsadek; Nafady, Nivien Allam; Khalaf, David Mamdouh; Morsy, Fatthy Mohamed

    2014-01-20

    Egyptian soils are generally characterized by slightly alkaline to alkaline pH values (7.5-8.7) which are mainly due to its dry environment. In arid and semi-arid regions, salts are less concentrated and sodium dominates in carbonate and bicarbonate forms, which enhance the formation of alkaline soils. Alkaline soils have fertility problems due to poor physical properties which adversely affect the growth and the yield of crops. Therefore, this study was devoted to investigating the synergistic interaction of Rhizobium and arbuscular mycorrhizal fungi for improving growth of faba bean grown in alkaline soil. A total of 20 rhizobial isolates and 4 species of arbuscular mycorrhizal fungi (AMF) were isolated. The rhizobial isolates were investigated for their ability to grow under alkaline stress. Out of 20 isolates 3 isolates were selected as tolerant isolates. These 3 rhizobial isolates were identified on the bases of the sequences of the gene encoding 16S rRNA and designated as Rhizobium sp. Egypt 16 (HM622137), Rhizobium sp. Egypt 27 (HM622138) and Rhizobium leguminosarum bv. viciae STDF-Egypt 19 (HM587713). The best alkaline tolerant was R. leguminosarum bv. viciae STDF-Egypt 19 (HM587713). The effect of R. leguminosarum bv. viciae STDF-Egypt 19 and mixture of AMF (Acaulospora laevis, Glomus geosporum, Glomus mosseae and Scutellospora armeniaca) both individually and in combination on nodulation, nitrogen fixation and growth of Vicia faba under alkalinity stress were assessed. A significant increase over control in number and mass of nodules, nitrogenase activity, leghaemoglobin content of nodule, mycorrhizal colonization, dry mass of root and shoot was recorded in dual inoculated plants than plants with individual inoculation. The enhancement of nitrogen fixation of faba bean could be attributed to AMF facilitating the mobilization of certain elements such as P, Fe, K and other minerals that involve in synthesis of nitrogenase and leghaemoglobin. Thus it is

  17. Solvation of apolar compounds in protic ionic liquids: the non-synergistic effect of electrostatic interactions and hydrogen bonds.

    Science.gov (United States)

    Sedov, I A; Magsumov, T I; Salikov, T M; Solomonov, B N

    2017-09-27

    The solvation properties of protic ionic liquids such as alkylammonium salts are still virtually uncharacterized. Both electrostatic interactions between charged particles and hydrogen bond networks in a solvent are known to hinder the solubility of apolar species. Protic ionic liquids can be a priori expected to dissolve hydrocarbons worse than aprotic ionic liquids which do not form hydrogen bonds between the ions. We measured the limiting activity coefficients of several alkanes and alkylbenzenes in propylammonium and butylammonium nitrates at 298 K. Surprisingly, we observed the tendency of higher solubility than for the same compounds in aprotic ionic liquids with a similar molar volume. The calculations of the excess Gibbs free energies using test particle insertions into the snapshots of molecular dynamics trajectories reproduced lower values in protic rather than in aprotic ionic liquids for both methane molecules and hard sphere solutes. This can be explained by the favorable solvation of apolar species in the apolar domain of nanostructured PILs. For the first time, we point out at the essential difference between the solvation properties of two types of ionic liquids and prove that it arises from the cavity formation term.

  18. Worlds Apart – Transcriptome Profiles of Key Oral Microbes in the Periodontal Pocket Compared to Single Laboratory Culture Reflect Synergistic Interactions

    Directory of Open Access Journals (Sweden)

    Zhi-Luo Deng

    2018-02-01

    Full Text Available Periodontitis is a worldwide prevalent oral disease which results from dysbiosis of the periodontal microbiome. Some of the most active microbial players, e.g., Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum, have extensively been studied in the laboratory, but it is unclear to which extend these findings can be transferred to in vivo conditions. Here we show that the transcriptional profiles of P. gingivalis, T. denticola, and F. nucleatum in the periodontal niche are distinct from those in single laboratory culture and exhibit functional similarities. GO (gene ontology term enrichment analysis showed up-regulation of transporters, pathogenicity related traits and hemin/heme uptake mechanisms for all three species in vivo. Differential gene expression analysis revealed that cysteine proteases, transporters and hemin/heme-binding proteins were highly up-regulated in the periodontal niche, while genes involved in DNA modification were down-regulated. The data suggest strong interactions between those three species regarding protein degradation, iron up-take, and mobility in vivo, explaining their enhanced synergistic pathogenicity. We discovered a strikingly high frequency of Single Nucleotide Polymorphisms (SNPs in vivo. For F. nucleatum we discovered a total of 127,729 SNPs in periodontal niche transcripts, which were found in similar frequency in health and disease and covered the entire genome, suggesting continuous evolution in the host. We conclude that metabolic interactions shape gene expression in vivo. Great caution is required when inferring pathogenicity of microbes from laboratory data, and microdiversity is an important adaptive trait of natural communities.

  19. Enhanced 3-sulfanylhexan-1-ol production in sequential mixed fermentation with Torulaspora delbrueckii/Saccharomyces cerevisiae reveals a situation of synergistic interaction between two industrial strains

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    Philippe eRenault

    2016-03-01

    Full Text Available The aim of this work was to study the volatile thiol productions of 2 industrial strains of Torulaspora delbrueckii and Saccharomyces cerevisiae during alcoholic fermentation (AF of Sauvignon Blanc must. In order to evaluate the influence of the inoculation procedure, sequential and simultaneous mixed cultures were carried out and compared to pure cultures of T. delbrueckii and S. cerevisiae. The results confirmed the inability of T. delbrueckii to release 4-methyl-4-sulfanylpentan-2-one (4MSP and its low capacity to produce 3-sulfanylhexyl acetate (3SHA, as already reported in previous studies. A synergistic interaction was observed between the two species, resulting in higher levels of 3SH (3-sulfanylhexan-1-ol and its acetate when S. cerevisiae was inoculated 24 hours after T. delbrueckii, compared to the pure cultures. To elucidate the nature of the interactions between these 2 species, the yeast population kinetics were examined and monitored, as well as the production of 3SH, its acetate and their related non-odorous precursors: Glut-3SH (glutathionylated conjugate precursor and Cys-3SH (cysteinylated conjugate precursor. For the first time, it was suggested that, unlike, S. cerevisiae, which is able to metabolize the two precursor forms, T. delbrueckii was only able to metabolize the glutathionylated precursor. Consequently, the presence of T. delbrueckii during mixed fermentation led to an increase in Glut-3SH degradation and Cys-3SH production. This overproduction was dependent on the T. delbrueckii biomass. In sequential culture, thus favouring T. delbrueckii development, the higher availability of Cys-3SH throughout AF (alcoholic fermentation resulted in more abundant 3SH and 3SHA production by S. cerevisiae

  20. Oviposition in Sweet Cherry by Reproductively Mature Western Cherry Fruit Fly (Tephritidae:Diptera) Fed Spinosad and Neonicotinoid Insecticide Baits

    Science.gov (United States)

    Western cherry fruit fly, Rhagoletis indifferens Curran, is a major pest of cherry, Prunus avium (L.) L., in the Pacific Northwest of the U.S. Spinosad bait is applied weekly to kill flies before they develop eggs, but its effects on oviposition by flies that are reproductively mature are unknown. ...

  1. Effects of spinosad on honey bees (Apis mellifera: Findings from over ten years of testing and commercial use

    Directory of Open Access Journals (Sweden)

    Miles, Mark J.

    2012-10-01

    Full Text Available Background: Spinosad is widely used as an insecticide in crop protection against thysanopteran, lepidopteran and dipteran species. As such it is intrinsically toxic to insects and among them to the honey bee (Apis mellifera. An updated risk assessment is presented in the context of the regulatory evaluation of spinosad products and is in accordance with the latest recommendation of regulatory guidance documents. Results: The intrinsic toxicity to the honey bee as observed in laboratory conditions through oral and contact tests on adults does not appear to impair honey bee colonies when exposed to treated attractive crops in tunnel conditions. Reasons for this could include reduced availability of residues of the product on plant surface compared to laboratory conditions, together with a fast dissipation from treated plants and the absence of active degradation products.Conclusions: Spinosad products present a negligible impact on honey bees when used under the current label recommendations and conditions of agricultural use. This conclusion deduced from data available for the regulatory risk assessment has been confirmed by the feedback of surveys on incidents, which address the potential impact of spinosad products under realistic conditions of exposure, including other environmental and chemical factors that are common in cropped areas.

  2. Efficacy of two anthelmintic treatments, spinosad/milbemycin oxime and ivermectin/praziquantel in dogs with natural Toxocara spp. infection.

    Science.gov (United States)

    Heredia Cardenas, Rafael; Romero Núñez, Camilo; Miranda Contreras, Laura

    2017-11-30

    Toxocara canis is one of the most important zoonotic parasites of dogs. The aim of the present study was to compare the efficacy of spinosad/milbemycin oxime and ivermectin/praziquantel in dogs naturally infected with Toxocara spp. We studied 200 dogs with a positive diagnosis of Toxocara spp. Through coproparasitoscopic analysis, two study groups of 100 dogs each were assigned: spinosad/milbemycin oxime at a dose of 30-60mg/kg and 0.75-1.0mg/kg, respectively, or ivermectin/praziquantel administered at a dose of 0.2mg/kg and 5mg/kg, respectively. Both groups received a single dose. Three stool samples, one at day 0 before treatment, and at 14 and 28days post-treatment were examined using concentration-flotation techniques. In both treatments, the number of Toxocara spp. eggs decreased; with spinosad/milbemycin oxime treatment, eggs decreased by 87% at 14days (P=0.008) and 94% at 28days after treatment, compared with 71% at day 14 and 88% at day 28 in dogs medicated with ivermectin/praziquantel. The spinosad/milbemycin oxime treated group showed a greater decrease in the number of Toxocara spp. positive dogs compared to the group receiving ivermectin/praziquantel. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Temperature-mediated kill and oviposition of Western Cherry Fruit Fly (Diptera: Tephritidae) in the presence of Spinosad

    Science.gov (United States)

    Western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is a quarantine pest of sweet cherry (Prunus avium (L.) L.) that is managed using insecticides, including spinosad, an organic compound that can be applied in low spray volumes. Identifying factors that can increase the...

  4. Attraction and Mortality of Oriental Fruit Flies (Diptera: Tephritidae) to SPLAT-MAT- Methyl Eugenol with Spinosad

    Science.gov (United States)

    Studies were conducted in Hawaii to quantify attraction and feeding responses resulting in mortality of male oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), to SPLAT-MAT-methyl eugenol (ME) with spinosad in comparison with Min-U-Gel-ME with naled (Dibrom). Our approach invol...

  5. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.

  6. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    International Nuclear Information System (INIS)

    Khatami, Mahin

    2014-01-01

    dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health

  7. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2 and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine, facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-b, PGE2. M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9 is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin and tumorigenic (Yang properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.

  8. Interactions within a [ionic liquid + poly(ethylene glycol)] mixture revealed by temperature-dependent synergistic dynamic viscosity and probe-reported microviscosity.

    Science.gov (United States)

    Trivedi, Shruti; Pandey, Siddharth

    2011-06-09

    Mixtures of ionic liquid (IL) with poly(ethylene glycol) (PEG) may afford media with favorable properties. Dynamic viscosities of mixtures of a common and popular IL 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF(6)]) with PEGs of average molecular weight (MW) 200 (PEG200), average MW 400 (PEG400), number-average MW M(n) 570-630 (PEG600), and number-average MW M(n) 950-1050 (PEG1000) over a complete composition range at 10° intervals in the temperature range of 10-90 °C are measured. The temperature dependence of the dynamic viscosity shows ([bmim][PF(6)] + PEG) mixtures to behave as Newtonian fluids and is found to follow Arrhenius-type behavior. In the IL-rich region, excess logarithmic viscosities for the ([bmim][PF(6)] + PEG200) mixture are found to be negative and independent of the temperature. Mixtures of ([bmim][PF(6)] + PEG600) and ([bmim][PF(6)] + PEG1000) show rare and unusual viscosity "synergism" or "hyperviscosity" in the sense that the mixture viscosity is observed to be significantly higher than the viscosity of both the neat components forming the mixture, giving rise to large positive excess logarithmic viscosities. These positive excess logarithmic viscosities decrease with increasing temperature. Formation of extensive H-bonding between the IL and PEG more than compensates for the losses in Coulombic attractive and van der Waals interactions within [bmim][PF(6)] and PEG600/PEG1000, respectively, giving rise to viscosity synergism. This compensation is not enough for ([bmim][PF(6)] + PEG200) and ([bmim][PF(6)] + PEG400) mixtures. The evidence for H-bonding in the mixtures is provided by FTIR absorbance data. The product of the monomer-to-excimer emission intensity ratio and the lifetime of the intramolecular excimer fluorescence of a microfluidity probe, 1,3-bis(1-pyrenyl)propane (BPP), is used as a reflection of the microviscosity of the mixture at different temperatures. The microviscosity shows synergistic effects in all four

  9. Characterization of the synergistic interaction between Beauveria bassiana strain GHA and Bacillus thuringiensis morrisoni strain tenebrionis applied against Colorado potato beetle larvae.

    Science.gov (United States)

    Wraight, S P; Ramos, M E

    2017-03-01

    Studies were undertaken to further characterize the previously identified synergistic activity of Bacillus thuringiensis- and Beauveria bassiana-based biopesticides against Colorado potato beetle (CPB). A flowable concentrate of B. thuringiensis morrisoni strain tenebrionis (Bt) (Novodor® FC) and a wettable powder of B. bassiana strain GHA (Bb) (Mycotrol® 22WP) were applied against CPB larval populations infesting potato in field plots. Novodor FC and an oil-dispersion formulation of Bb (Mycotrol ES) were applied against second-instar CPB larvae on potted potato plants in greenhouse tests under low relative humidity (RH), variable-temperature conditions. Each pathogen was applied alone and in combination (tank-mixed) with the other pathogen. In the field tests, each biopesticide was also combined with the spray-carrier (formulation without active ingredient) of the other pathogen. Results from the greenhouse tests showed that under warm, dry conditions, low activity of Mycotrol was counterbalanced by high activity of the Novodor, and under cool, somewhat more humid conditions, low Novodor activity was balanced by high activity of Mycotrol, with the result being a constant level of synergism (CPB mortality ca. 20 percentage points higher than predicted by independent action). Similar levels of synergism were observed under the markedly different conditions of the field and greenhouse environments, and the synergism was confirmed as arising from interaction of the two micobes, as the Bt spray carrier had no significant effect on efficacy of the Mycotrol product and the Bb spray carrier had no effect on the efficacy of Novodor. The great capacity of these two control agents to act in concert to control CPB is well documented (the fast-acting, toxic Bt acting to protect potato crops from defoliation and the slow-acting Bb reducing survival to the adult stage). These finding further underscore the strong complementary action of these agents applied jointly against CPB

  10. DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin.

    Directory of Open Access Journals (Sweden)

    Xilin Sun

    Full Text Available Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI. Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group, Abraxane only (A group, and sequential treatment with Abraxane followed by cisplatin (A-P group. Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.

  11. Evaluation of SPLAT with spinosad and methyl eugenol or cue-lure for "attract-and-kill" of oriental and melon fruit flies (Diptera: Tephritidae) in Hawaii.

    Science.gov (United States)

    Vargas, Roger I; Stark, John D; Hertlein, Mark; Neto, Agenor Mafra; Coler, Reginald; Piñero, Jaime C

    2008-06-01

    Specialized Pheromone and Lure Application Technology (SPLAT) methyl eugenol (ME) and cue-lure (C-L) "attract-and-kill" sprayable formulations containing spinosad were compared with other formulations under Hawaiian weather conditions against oriental fruit fly, Bactrocera dorsalis (Hendel), and melon fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae), respectively. Field tests were conducted with three different dispensers (Min-U-Gel, Acti-Gel, and SPLAT) and two different insecticides (naled and spinosad). SPLAT ME with spinosad was equal in performance to the standard Min-U-Gel ME with naled formulation up to 12 wk. SPLAT C-L with spinosad was equal in performance to the standard Min-U-Gel C-L with naled formulation during weeks 7 to12, but not during weeks 1-6. In subsequent comparative trials, SPLAT ME + spinosad compared favorably with the current standard of Min-U-Gel ME + naled for up to 6 wk, and it was superior from weeks 7 to 12 in two separate tests conducted in a papaya (Carica papaya L.) orchard and a guava (Psidium guajava L.) orchard, respectively. In outdoor paired weathering tests (fresh versus weathered), C-L dispensers (SPLAT + spinosad, SPLAT + naled, and Min-U-Gel + naled) were effective up to 70 d. Weathered ME dispensers with SPLAT + spinosad compared favorably with SPLAT + naled and Min-U-Gel + naled, and they were equal to fresh dispensers for 21-28 d, depending on location. Our current studies indicate that SPLAT ME and SPLAT C-L sprayable attract-and-kill dispensers containing spinosad are a promising substitute for current liquid organophosphate insecticide formulations used for areawide suppression of B. dorsalis and B. cucurbitae in Hawaii.

  12. Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Loreto Sanhueza

    Full Text Available Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics. Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the

  13. The α6 nicotinic acetylcholine receptor subunit of Frankliniella occidentalis is not involved in resistance to spinosad.

    Science.gov (United States)

    Hou, Wenjie; Liu, Qiulei; Tian, Lixia; Wu, Qingjun; Zhang, Youjun; Xie, Wen; Wang, Shaoli; Miguel, Keri San; Funderburk, Joe; Scott, Jeffrey G

    2014-05-01

    Insects evolve resistance which constrains the sustainable use of insecticides. Spinosyns, a class of environmentally-friendly macrolide insecticides, is not an exception. The mode of inheritance and the mechanisms of resistance to spinosad (the most common spinosyn insecticide) in Frankliniella occidentalis (Western flower thrips, WFT) were investigated in this study. Resistance (170,000-fold) was autosomal and completely recessive. Recent studies showed that deletion of the nicotinic acetylcholine receptor α6 subunit gene resulted in strains of Drosophila melanogaster, Plutella xylostella and Bactrocera dorsalis that are resistant to spinosad, indicating that nAChRα6 subunit maybe important for the toxic action of this insecticide. Conversely, a G275E mutation of this subunit in F. occidentalis was recently proposed as the mechanism of resistance to spinosad. We cloned and characterized nAChRα6 from three susceptible and two spinosad resistant strains from China and the USA. The Foα6 cDNA is 1873bp and the open reading frame is 1458bp which encodes 485 amino acid residues with a predicted molecular weight of 53.5-kDa, the 5' and 3' UTRs are 121 and 294bp, respectively. There was no difference in the cDNA sequence between the resistant and susceptible thrips, suggesting the G275E mutation does not confer resistance in these populations. Ten isoforms of Foα6, arising from alternative splicing, were isolated and did not differ between the spinosad-susceptible and resistant strains. Quantitative real time PCR analysis showed Foα6 was highly expressed in the first instar larva, pupa and adult, and the expression levels were 3.67, 2.47, 1.38 times that of the second instar larva. The expression level was not significantly different between the susceptible and resistant strains. These results indicate that Foα6 is not involved in resistance to spinosad in F. occidentalis from China and the USA. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Nanotechnology for Multimodal Synergistic Cancer Therapy.

    Science.gov (United States)

    Fan, Wenpei; Yung, Bryant; Huang, Peng; Chen, Xiaoyuan

    2017-11-22

    The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely "1 + 1 > 2") effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furthermore, the featured applications of multimodal synergistic therapy in overcoming tumor multidrug resistance, hypoxia, and metastasis will also be discussed in detail, which may provide new ways for the efficient regression and even elimination of drug resistant, hypoxic solid, or distant metastatic tumors. Finally, some design tips for multifunctional nanomaterials and an outlook on the future development of multimodal synergistic therapy will be provided, highlighting key scientific issues and technical challenges and requiring remediation to accelerate clinical translation.

  15. A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor α6 subunit confers high-level resistance to spinosad in Plutella xylostella.

    Science.gov (United States)

    Wang, Jing; Wang, Xingliang; Lansdell, Stuart J; Zhang, Jianheng; Millar, Neil S; Wu, Yidong

    2016-04-01

    Spinosad is a macrocyclic lactone insecticide that acts primarily at the nicotinic acetylcholine receptors (nAChRs) of target insects. Here we describe evidence that high levels of resistance to spinosad in the diamondback moth (Plutella xylostella) are associated with a three amino acid (3-aa) deletion in the fourth transmembrane domain (TM4) of the nAChR α6 subunit (Pxα6). Following laboratory selection with spinosad, the SZ-SpinR strain of P. xylostella exhibited 940-fold resistance to spinosad. In addition, the selected insect population had 1060-fold cross-resistance to spinetoram but, in contrast, no cross-resistance to abamectin was observed. Genetic analysis indicates that spinosad resistance in SZ-SpinR is inherited as a recessive and autosomal trait, and that the 3-aa deletion (IIA) in TM4 of Pxα6 is tightly linked to spinosad resistance. Because of well-established difficulties in functional expression of cloned insect nAChRs, the analogous resistance-associated deletion mutation was introduced into a prototype nAChR (the cloned human α7 subunit). Two-electrode voltage-clamp recording with wild-type and mutated nAChRs expressed in Xenopus laevis oocytes indicated that the mutation causes a complete loss of agonist activation. In addition, radioligand binding studies indicated that the 3-aa deletion resulted in significantly lower-affinity binding of the extracellular neurotransmitter-binding site. These findings are consistent with the 3-amino acid (IIA) deletion within the transmembrane domain of Pxα6 being responsible for target-site resistance to spinosad in the SZ-SpinR strain of P. xylostella. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Mechanically enforced bond dissociation reports synergistic influence of Mn2+ and Mg2+ on the interaction between integrin α7β1 and invasin

    DEFF Research Database (Denmark)

    Ligezowska, Agnieszka; Boye, Kristian; Eble, Johannes A.

    2011-01-01

    addition of these cations to the measurement buffer, we observe a pronounced increase in the force necessary to separate integrin and invasin coated beads. Both ions were found to work synergistically. With free invasin in the measurement buffer we furthermore observe that competitive blocking of binding...... sites overrides the increase in binding strength of individual beads. We show that this is due to a very strong dependence of bond affinity on divalent ions. Our study illustrates the importance of divalent ions for the regulation of force transmission by integrin ligand bonds on the molecular level...

  17. [Effects of Total Nitrogen and BOD5/TN on Anaerobic Ammonium Oxidation-Denitrification Synergistic Interaction of Mature Landfill Leachate in Aged Refuse Bioreactor].

    Science.gov (United States)

    Yang, Ying-ying; Chen, Yi; Lj, Ming-jie; Xie, Bing

    2015-04-01

    Mature landfill leachate, featured with high ammonium (NH4+) content and low biodegrade ability (low BOD5/COD ratio), is hard to be treated. This study mainly focused on the effects of influent TN (total nitrogen) loading and BOD5/TN ratios on the nitrogen removal efficiency of landfill leachate by landfill bioreactors. The results showed that when the influent total nitrogen loading was in the range of 15 g x (m3 x d)(-1) to 25 g x (m3 x d)(-1), the TN removal loading could remain stable between 10 g x (m3 x d)(-1) and 12 g x (m3 x d)(-1), while the TN removal efficiency decreased from 67.7% to 60.2% with the increasing loading. Therefore, TN loading shocks would lower the bioreactor's TN removal rate, but would not affect its TN removal loading. When the influent BOD5/TN ratio was increased from 0.3 to 0.4 and the TN loading was controlled at 9 g x (m3 x d)(-1), the TN removal rates were increased from 79.9% to 89.9% and 86.2% in anaerobic and aerobic, respectively. This implied that properly enhancing BOD5/TN ratio could significantly increase the TN removal efficiency of the bioreactor, and the effect was more significant under anaerobic condition. Analysis of nitrogen removal pathways showed that denitrification and anammox could take place synergistically in landfill bioreactor.

  18. Variation in susceptibility of field strains of three stored grain insect species to spinosad and chlorpyrifos-methyl plus deltamethrin on hard red winter wheat

    Science.gov (United States)

    Spinosad and chlorpyrifos-methyl plus deltamethrin efficacy at labeled rates on hard red winter wheat was evaluated against 11 strains of the red flour beetle, Tribolium castaneum (Herbst); six strains of the sawtoothed grain beetle, Oryzaephilus surinamensis (L.); and two strains of the lesser grai...

  19. Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole.

    NARCIS (Netherlands)

    Afeltra, J.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2004-01-01

    To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF),

  20. Attraction and mortality of Bactrocera dorsalis (Diptera: Tephritidae) to STATIC Spinosad ME weathered under operational conditions in California and Florida: a reduced-risk male annihilation treatment.

    Science.gov (United States)

    Vargas, Roger I; Souder, Steven K; Hoffman, Kevin; Mercogliano, Juan; Smith, Trevor R; Hammond, Jack; Davis, Bobbie J; Brodie, Matt; Dripps, James E

    2014-08-01

    Studies were conducted in 2013-2014 to quantify attraction, feeding, and mortality of male oriental fruit flies, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), to STATIC Spinosad ME a reduced-risk male annihilation treatment (MAT) formulation consisting of an amorphous polymer matrix in combination with methyl eugenol (ME) and spinosad compared with the standard treatment of Min-U-Gel mixed with ME and naled (Dibrom). Our approach used a behavioral methodology for evaluation of slow-acting reduced-risk insecticides. ME treatments were weathered for 1, 7, 14, 21, and 28 d under operational conditions in California and Florida and shipped to Hawaii for bioassays. In field tests using bucket traps to attract and capture wild males, and in toxicity studies conducted in 1-m(3) cages using released males of controlled ages, STATIC Spinosad ME performed equally as well to the standard formulation of Min-U-Gel ME with naled for material aged up to 28 d in both California and Florida. In laboratory feeding tests in which individual males were exposed for 5 min to the different ME treatments, mortality induced by STATIC Spinosad ME recorded at 24 h did not differ from mortality caused by Min-U-Gel ME with naled at 1, 7, 14, and 21 d in California and was equal to or higher for all weathered time periods in Florida during two trials. Spinosad has low contact toxicity, and when mixed with an attractant and slow release matrix, offers a reduced-risk alternative for eradication of B. dorsalis and related ME attracted species, without many of the potential negative effects to humans and nontargets associated with broad-spectrum contact insecticides such as naled.

  1. Synergistic effect of non-covalent interaction in colloidal nematic liquid crystal doped with magnetic functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Dalir, Nima; Javadian, Soheila

    2018-03-01

    Single-walled carbon nanotubes (SWCNTs), CNT@Fe3O4, and Fe3O4 nanocomposites were doped to eutectic uniaxial nematic liquid crystal (NLC's) (E5CN7) to improve physiochemical properties such as phase transition temperature, activation energy (Ea), dielectric anisotropy, and electro-optical properties. The thermal study of nematic phase shows a decrease in the nematic to isotropic phase transition temperature as CNT is doped. However, higher doping concentration of CNTs leads to the further increase in transition temperature. The anchoring effect or π-π interaction plays a key role in N-I phase transition. The functionalization of SWCNTs with Fe3O4 diminishes the CNT aggregation while the magnetic susceptibility is increased. The functionalized CNT doping to NLC's decrease significantly the phase transition temperature compared to doping of non-functionalized CNTs. Attractive interaction between guest and host molecules by magnetic and geometry effect increased the enthalpy and entropy of phase transition in the SWCNT@Fe3O4 sample compared to non-functionalized CNT doped system. Also, the Ea values are decreased as SWCNT@Fe3O4 is doped to pure E5CN7. The difference of N-I phase transition temperature was observed in Fe3O4 and CNT@Fe3O4 compared to SWCNT doped systems. Finally, dielectric anisotropy was increased in the doped system compared to pure NLC.

  2. Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats.

    Science.gov (United States)

    Ortiz, Mario I; Fernández-Martínez, Eduardo; Soria-Jasso, Luis Enrique; Lucas-Gómez, Isaac; Villagómez-Ibarra, Roberto; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

    2016-03-01

    Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, α-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but α-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Evaluation of sarolaner and spinosad oral treatments to eliminate fleas, reduce dermatologic lesions and minimize pruritus in naturally infested dogs in west Central Florida, USA.

    Science.gov (United States)

    Dryden, Michael W; Canfield, Michael S; Niedfeldt, Emily; Kinnon, Amanda; Kalosy, Kimberly; Smith, Amber; Foley, Kaitlin M; Smith, Vicki; Bress, Todd S; Smith, Nicole; Endrizzi, Mike; Login, Joyce

    2017-08-17

    An in-home investigation of naturally flea infested dogs was conducted in West Central Florida, USA to evaluate and compare the effectiveness of two different oral flea adulticides to control flea infestations, minimize dermatologic lesions and reduce pruritus over an 8-week period. Twenty-nine dogs living in 19 homes and another 26 dogs residing in 16 different homes were orally administered either a sarolaner or spinosad chewable, respectively on day 0 and once between days 28-30. Products were administered by study personnel according to label directions. Flea populations on dogs were estimated using visual area counts and flea infestations in the indoor premises were assessed using intermittent-light flea traps on days 0, 7, 14, 21 and once between days 28-30, 40-45, and 56-60. Assessments of dermatologic lesions were conducted monthly during the study and severity of pruritus was evaluated throughout the study on the same schedule as flea counts were conducted. Concurrent treatments for existing skin disease were not allowed. The administration of sarolaner or spinosad reduced flea populations on dogs by 99.0% and 97.3%, respectively within 7 days. Flea infestations on the sarolaner- and spinosad-treated dogs were reduced by > 99% at every counting period from day 14 post-treatment through the end of the 8-week study. At the end of the study 96.4 and 92.0% of the dogs treated with sarolaner and spinosad, respectively were flea-free. Flea populations in the indoor premises were also markedly reduced the end of the study, with 100 and 99.8% reductions in flea trap counts in the sarolaner and spinosad treatment groups, respectively. FAD lesion scores, atopic dermatitis lesions scores (CADESI-4) and pruritus severity scores were also markedly improved with both formulations. An in-home clinical field study conducted during the summer of 2016 in subtropical Florida demonstrated that two-monthly administrations of either sarolaner or spinosad chewables almost

  4. Synergistic interaction between wavelength of light and concentration of H₂O₂ in bactericidal activity of photolysis of H₂O₂.

    Science.gov (United States)

    Toki, Toshihide; Nakamura, Keisuke; Kurauchi, Michiko; Kanno, Taro; Katsuda, Yusuke; Ikai, Hiroyo; Hayashi, Eisei; Egusa, Hiroshi; Sasaki, Keiichi; Niwano, Yoshimi

    2015-03-01

    The present study aimed to evaluate the interaction between wavelength of light in the range of ultra violet A-visible and concentration of H2O2 in the reaction of photolysis of H2O2 from the point of view of hydroxyl radical (·OH) generation and the bactericidal activity. Light emitting diodes (LEDs) emitting the light at wavelengths of 365, 385, 400 and 465 nm were used at an irradiance of 1000 mW/cm(2). H2O2 was used at the final concentrations of 0, 250, 500, and 1000 mM. Quantitative analysis of ·OH generated by the LED irradiation of H2O2 were performed using an electron spin resonance-spin trapping technique. In a bactericidal assay, a bacterial suspension of Staphylococcus aureus prepared in sterile physiological saline was irradiated with the LEDs. The bactericidal activity of each test condition was evaluated by viable counts. When H2O2 was irradiated with the LEDs, ·OH was generated and bacteria were killed dependently on the concentration of H2O2 and the wavelength of LED. The two-way analysis of variance revealed that the wavelength, the H2O2 concentration and their interaction significantly affected the yield of ·OH and the bactericidal activity of the photolysis of H2O2. Therefore, it is suggested that bactericidal activity of photolysis of H2O2 could be enhanced by controlling the wavelength and the concentration of H2O2, which may contributes to shortening the treatment time and/or to reducing the concentration of H2O2. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. Synergistic interactions between RAD5, RAD16, and RAD54, three partially homologous yeast DNA repair genes each in a different repair pathway

    International Nuclear Information System (INIS)

    Glassner, B.J.; Mortimer, R.K.

    1994-01-01

    Considerable homology has recently been noted between the proteins encoded by the RAD5, RAD16 and RAD54 genes of Saccharomyces cerevisiae. These genes are members of the RAD6, RAD3 and RAD50 epistasis groups, respectively, which correspond to the three major DNA repair pathways in yeast. These proteins also share homology with other eucaryotic proteins, including those encoded by SNF2 and MO1 of yeast, brahma and lodestar of Drosophila and the human ERCC6 gene. The homology shares features with known helicases, suggesting a newly identified helicase subfamily. We have constructed a series of congenic single-, double- and triple-deletion mutants involving RAD5, RAD16 and RAD54 to examine the interactions between these genes. Each deletion mutation alone has only a moderate effect on survival after exposure to UV radiation. Each pairwise-double mutant exhibits marked synergism. The triple-deletion mutant displays further synergism. These results confirm the assignment of the RAD54 gene to the RAD50 epistasis group and suggest that the RAD16 gene plays a larger role in DNA repair after exposure to UV radiation than has been suggested previously. Additionally, the proteins encoded by RAD5, RAD16, and RAD54 may compete for the same substrate after damage induced by UV radiation, possibly at an early step in their respective pathways. 49 refs., 6 figs., 2 tabs

  6. Synergistic effects in mixed Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Holler, B.M.; Molin, Søren

    2006-01-01

    the pathways governing development of more complex heterogeneous communities. In this study, we established a laboratory model where biofilm-stimulating effects due to interactions between genetically diverse strains of Escherichia coli were monitored. Synergistic induction of biofilm formation resulting from...... the cocultivation of 403 undomesticated E. coli strains with a characterized E. coli K-12 strain was detected at a significant frequency. The survey suggests that different mechanisms underlie the observed stimulation, yet synergistic development of biofilm within the subset of E. coli isolates (n = 56) exhibiting...... the strongest effects was most often linked to conjugative transmission of natural plasmids carried by the E. coli isolates (70%). Thus, the capacity of an isolate to promote the biofilm through cocultivation was (i) transferable to the K-12 strain, (ii) was linked with the acquisition of conjugation genes...

  7. Determining lower threshold concentrations for synergistic effects.

    Science.gov (United States)

    Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas; Nørgaard, Katrine Banke; Mayer, Philipp; Cedergreen, Nina

    2017-01-01

    Though only occurring rarely, synergistic interactions between chemicals in mixtures have long been a point of focus. Most studies analyzing synergistic interactions used unrealistically high chemical concentrations. The aim of the present study is to determine the threshold concentration below which proven synergists cease to act as synergists towards the aquatic crustacean Daphnia magna. To do this, we compared several approaches and test-setups to evaluate which approach gives the most conservative estimate for the lower threshold for synergy for three known azole synergists. We focus on synergistic interactions between the pyrethroid insecticide, alpha-cypermethrin, and one of the three azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia magna immobilization. Three different experimental setups were applied: A standard 48h acute toxicity test, an adapted 48h test using passive dosing for constant chemical exposure concentrations, and a 14-day test. Synergy was defined as occuring in mixtures where either EC 50 values decreased more than two-fold below what was predicted by concentration addition (horizontal assessment) or as mixtures where the fraction of immobile organisms increased more than two-fold above what was predicted by independent action (vertical assessment). All three tests confirmed the hypothesis of the existence of a lower azole threshold concentration below which no synergistic interaction was observed. The lower threshold concentration, however, decreased with increasing test duration from 0.026±0.013μM (9.794±4.897μgL -1 ), 0.425±0.089μM (145.435±30.46μgL -1 ) and 0.757±0.253μM (249.659±83.44μgL -1 ) for prochloraz, propiconazole and epoxiconazole in standard 48h toxicity tests to 0.015±0.004μM (5.651±1.507μgL -1 ), 0.145±0.025μM (49.619±8.555μgL -1 ) and 0.122±0.0417μM (40.236±13.75μgL -1 ), respectively, in the 14-days tests. Testing synergy in relation to concentration addition provided

  8. Synergistic Synthetic Biology: Units in Concert

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

  9. Synergistic Synthetic Biology: Units in Concert

    International Nuclear Information System (INIS)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  10. Synergistic Moel of Organizational Structure.

    Science.gov (United States)

    Wolfe, Richard O.

    1985-01-01

    Defines the concept of the synergistic model of organizational structure. The primary components of the model are cooperative action and job integration, which have as a direct result the increased energy in staff members using the model. (MD)

  11. Efficacy of milbemycin oxime in combination with spinosad in the treatment of larval and immature adult stages of Ancylostoma caninum and Toxocara canis in experimentally infected dogs.

    Science.gov (United States)

    Bowman, Dwight D; Reinemeyer, Craig R; Wiseman, Scott; Snyder, Daniel E

    2014-09-15

    Ancylostoma caninum and Toxocara canis are two important zoonotic parasites of dogs. The primary objective of these studies were to confirm the oral effectiveness of milbemycin oxime (MO) and spinosad in dogs experimentally infected with immature (L4 and immature adult) stages of T. canis or A. caninum. Both trials were conducted as randomized, blinded, placebo-controlled dose confirmation studies. Treatments using the intended European commercial tablet formulation of Trifexis were administered in a timeframe relative to inoculation so that effectiveness could be assessed against specific immature stages of A. caninum or T. canis. In each study on Day 0, each of 32, 3-4 month old dogs were inoculated with 250 infective eggs of T. canis or 300 infective L3 of the hookworm, A. caninum. All dogs were weighed before their scheduled treatment, randomized to 1 of the 4 treatment groups in each study (8 dogs/group). All dogs were fed just prior to dosing. For T. canis, dogs were treated orally with an MO/spinosad tablet on Day 14 or Day 24. For A. caninum, dogs were treated orally with an MO/spinosad tablet on Day 7 or Day 11. Corresponding control groups in each study received a placebo tablet. Dogs were necropsied 5 or 6 days after their respective treatments. The digestive tract was removed and processed to recover, count, and identify all stages. The GM worm count for the MO/spinosad tablet on Day 14 (L4 T. canis) was 0.0, with efficacy calculated as 100%; however, only 3 of 8 control dogs had adequate infections. The GM worm count for the MO/spinosad tablet on Day 24 (immature adult stage) was 0.30; efficacy calculated at 96.15%. This is based on 5 of the 8 control dogs with adequate infections. In the two A. caninum studies, GM worm counts for the MO/spinosad tablets on Day 7 (L4 efficacy) was 2.37 and 0.8 with efficacy calculated as 98.92% and 99.25%, respectively. The GM count for the group treated with the MO/spinosad combination on Day 11 (immature adult) was 6

  12. Field trials of spinosad as a replacement for naled, DDVP, and malathion in methyl eugenol and cue-lure bucket traps to attract and kill male oriental fruit flies and melon flies (Diptera: Tephritidae) in Hawaii.

    Science.gov (United States)

    Vargas, Roger I; Miller, Neil W; Stark, John D

    2003-12-01

    Spinosad was evaluated in Hawaii as a replacement for organophosphate insecticides (naled, dichlorvos [DDVP], and malathion) in methyl eugenol and cue-lure bucket traps to attract and kill oriental fruit fly, Bactrocera dorsalis Hendel, and melon fly, B. cucurbitae Coquillett, respectively. In the first and second methyl eugenol trials with B. dorsalis, naled was in the highest rated group for all evaluation periods (at 5, 10, 15, and 20 wk). Spinosad was equal to naled at 5 and 10 wk during both trials 1 and 2, and compared favorably with malathion during trial 2. During the first cue-lure trial with B. cucurbitae, naled and malathion were in the top rated group at 5, 10, 15, and 20 wk. Spinosad was equal to naled at 5 wk. During the second cue-lure trial, spinosad and naled were both in the top rated group at 10, 15, and 20 wk. Use of male lure traps with methyl eugenol or cue-lure had no effect on attraction of females into test areas. Our results suggest that spinosad, although not as persistent as naled or malathion, is safer to handle and a more environmentally friendly substitute for organophosphate insecticides in methyl eugenol and cue-lure traps for use in B. dorsalis and B. cucurbitae areawide integrated pest management programs in Hawaii.

  13. Azole Fungicides as Synergists in the Aquatic Environment

    DEFF Research Database (Denmark)

    Bjergager, Maj-Britt Andersen

    hazard.This PhD thesis evaluates the role of the so called azole fungicides as synergists in the aquaticenvironment through an assessment of the effect of sorption, time and azole concentration on theoccurrence and magnitude of synergistic interactions with pyrethroid insecticides towards...... the aquaticcrustacean Daphnia magna in both laboratory experiments and natural-like environments. In the PhDthesis, synergy is defined as happening in mixtures where either EC50 values decrease more than two-foldbelow the prediction by the model of Concentration Addition (horizontal assessment of synergy) or wherethe...... in stormwater runoff ordrain water and in the aquatic environment, the pesticides mainly occur in sorbed form. Sorption istraditionally considered to limit bioaccessibility and toxicity of hydrophobic compounds, hence,synergistic interactions may be limited in natural environments compared to laboratory studies...

  14. Residual Toxicity of Abamectin, Chlorpyrifos, Cyromazine, Indoxacarb and Spinosad on Liriomyza trifolii (Burgess (Diptera: Agromyzidae in Greenhouse Conditions

    Directory of Open Access Journals (Sweden)

    Ghasem Askari Saryazdi

    2012-01-01

    Full Text Available Liriomyza trifolii is an important pest of vegetable crops in many parts of the worldincluding Iran. In this study potted bean plants were sprayed with recommended fieldrates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residualactivities of these insecticides, the plants were infested with L. trifolii adults 2 hours; 1, 3,5, 7, 10, 15, 20, 25 and 35 days after insecticidal treatments. The adults were allowed to stayon treated plants for eight hours. The treated plants were kept in a greenhouse. Numberof feeding stipples and larval mines on leaves, as well as pupation and adult eclosion rateswere assessed. Two-way ANOVA procedure of SAS was used for statistical analysis andthe treatment means were separated using Duncan’s multiple range test. Abamectin andspinosad severely affected egg hatching and embryonic development. Eggs oviposited inleaves with residues of chlorpyrifos up to 5 days old, had reduced hatching. Larval developmentwas also, affected by residues of chlorpyrifos up to four weeks old. Indoxacarbreduced larval development and adult eclosion in treatments with up to 20 days old residues.Cyromazine had no effect on the number of larval mines, but, pupation was severelyhampered and adult eclosion was completely ceased even in treatments with five weeksold residues. Determining the residual activity of insecticides used for controlling this pestis useful in avoiding unnecessary treatments.

  15. Comparative in vitro evaluation of contact activity of fluralaner, spinosad, phoxim, propoxur, permethrin and deltamethrin against the northern fowl mite, Ornithonyssus sylviarum.

    Science.gov (United States)

    Mullens, Bradley A; Murillo, Amy C; Zoller, Hartmut; Heckeroth, Anja R; Jirjis, Faris; Flochlay-Sigognault, Annie

    2017-08-03

    Northern fowl mites (Ornithonyssus sylviarum) are obligate hematophagous ectoparasites of both feral birds and poultry, particularly chicken layers and breeders. They complete their entire life-cycle on infested birds while feeding on blood. Infestations of O. sylviarum are difficult to control and resistance to some chemical classes of acaricides is a growing concern. The contact susceptibility of O. sylviarum to a new active ingredient, fluralaner, was evaluated, as well as other compounds representative of the main chemical classes commonly used to control poultry mite infestations in Europe and the USA. Six acaricides (fluralaner, spinosad, phoxim, propoxur, permethrin, deltamethrin) were dissolved and serially diluted in butanol:olive oil (1:1) to obtain test solutions used for impregnation of filter paper packets. A carrier-only control was included. Thirty adult northern fowl mites, freshly collected from untreated host chickens, were inserted into each packet for continuous compound exposure. Mite mortality was assessed after incubation of the test packets for 48 h at 75% relative humidity and a temperature of 22 °C. Adult mite LC 50 /LC 99 values were 2.95/8.09 ppm for fluralaner, 1587/3123 ppm for spinosad, 420/750 ppm for phoxim and 86/181 ppm for propoxur. Permethrin and deltamethrin LC values could not be calculated due to lack of mortality observed even at 1000 ppm. Northern fowl mites were highly sensitive to fluralaner after contact exposure. They were moderately sensitive to phoxim and propoxur, and less sensitive to spinosad. Furthermore, the tested mite population appeared to be resistant to the pyrethroids, permethrin and deltamethrin, despite not being exposed to acaricides for at least 10 years.

  16. Comparative speed of kill of sarolaner (Simparica) and spinosad plus milbemycin oxime (Trifexis) against induced infestations of Ctenocephalides felis on dogs.

    Science.gov (United States)

    Six, Robert H; Everett, William R; Myers, Melanie R; Mahabir, Sean P

    2016-02-19

    Fleas are a ubiquitous ectoparasite infesting dogs and cause direct discomfort, allergic reactions and are responsible for the transmission of several pathogens. The rapid speed of kill of a parasiticide is important to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with spinosad in combination with milbemycin oxime (Trifexis) for 5 weeks after a single oral dose. Twenty-four dogs were randomly allocated to treatment with a single oral dose per product label of sarolaner (2 to 4 mg/kg), spinosad/milbemycin oxime (30 to 60 mg/kg / 0.2 to 0.4 mg/kg), or placebo based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy (reduction in live flea counts) of each treatment was determined at each time point relative to counts for placebo dogs. There were no adverse reactions to treatment. A single oral dose of sarolaner provided ≥94.0 % efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were eradicated from all dogs and they remained flea free at 24 h. Significantly greater numbers of live fleas were recovered from spinosad/milbemycin oxime-treated dogs at 8 h from Day 21 to Day 35 (P ≤ 0.0085), and at 12 and 24 h on Day 35 (P ≤ 0.0002). In this controlled laboratory evaluation, dogs treated with sarolaner had significantly fewer live fleas than spinosad/milbemycin oxime- treated dogs at 8 h after re-infestation from Day 21 after a single oral dose. The rapid and consistent kill of fleas after a single oral dose of sarolaner over 35 days indicates that this treatment should provide highly effective control of flea infestations

  17. Silica ecosystem for synergistic biotransformation

    OpenAIRE

    Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

    2016-01-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues...

  18. Developing an Agent-Based Drug Model to Investigate the Synergistic Effects of Drug Combinations.

    Science.gov (United States)

    Gao, Hongjie; Yin, Zuojing; Cao, Zhiwei; Zhang, Le

    2017-12-14

    The growth and survival of cancer cells are greatly related to their surrounding microenvironment. To understand the regulation under the impact of anti-cancer drugs and their synergistic effects, we have developed a multiscale agent-based model that can investigate the synergistic effects of drug combinations with three innovations. First, it explores the synergistic effects of drug combinations in a huge dose combinational space at the cell line level. Second, it can simulate the interaction between cells and their microenvironment. Third, it employs both local and global optimization algorithms to train the key parameters and validate the predictive power of the model by using experimental data. The research results indicate that our multicellular system can not only describe the interactions between the microenvironment and cells in detail, but also predict the synergistic effects of drug combinations.

  19. [Acute lethal effect of the commercial formulation of the insecticides Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus (Hymenoptera: Apidae) workers].

    Science.gov (United States)

    Riaño Jiménez, Diego; Cure, José Ricardo

    2016-12-01

    The effect of insecticides on bees has gained great attention, however, there are few studies that explore this issue on Neotropical bees. Bombus atratus is a neotropical species broadly distributed in Colombia and is considered an important pollinator of both Andean ecosystems and agroecosystems. However, as for many wild bees species, the effect of insecticides on B. atratus is unknow. In this study we determined the acute median lethal dose (LD50) of commercial formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen oxalate, widely used in Colombia to control several pests of important crops. The LD50 was carried out by oral and contact routes, following and modifying the EPPO and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for each route and insecticide, in a total of 25 medium-size workers for each dose by duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment; and data were analyzed with the Probit regression model. For Imidacloprid, contacts and oral LD50 were 0.048 µg/bee and 0.010 µg/bee, respectively. For Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 µg/bee and 0.056 µg/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 µg/bee; it was not possible to establish the LD50 for the contact route. The Hazard Quotient (HQ) and Index of Relative Toxicity indicated that all three active ingredients are highly toxic. We discussed the risk of the insecticides use on B. atratus, considering their chemical nature.

  20. Comparison of food-based attractants for Bactrocera invadens (Diptera: Tephritidae) and evaluation of mazoferm-spinosad bait spray for field suppression in mango.

    Science.gov (United States)

    Ekesi, Sunday; Mohamed, Samira; Tanga, Chrysantus M

    2014-02-01

    Catches of Bactrocera invadens Drew, Tsuruta, & White (Diptera: Tephritidae) in Multi-lure traps baited with six commercial food-based attractants, Mazoferm E802, Torula yeast, GF-120, Hymlure, Biolure, and Nulure were compared in mango orchards in Kenya. In 2007, Mazoferm E802 and Torula yeast were the most effective attractants and captured 2.4-2.6 times more females and 3.4-4.0 times more males than the standard Nulure. All attractants captured more females than males (ranging from 63 to 74%). In 2008, Mazoferm E802 was the most effective bait capturing 5.6 and 9.1 times more females and males, respectively, than the standard Nulure. Among all the attractants, in both years, Nulure captured the greatest proportion of females: 74% compared with 51-68% for the other attractants. In 2008, the use of Mazoferm E802 in combination with spinosad as a bait spray in mango orchards reduced B. invadens catches relative to the control by 87% within 4 wk and 90% within 8 wk. At harvest, the proportion of fruit infested was significantly lower in the treated orchards (8%) compared with the control orchards (59%). Estimated mango yield was significantly higher in orchards receiving the bait sprays (12,487 kg/ha) compared with control orchards (3,606 kg/ha). Based on bait spray costs, yield data, and monetary gains, a cost-benefit ratio of 1:9.1 was realized, which is acceptable for growers. In 2009, the experiment was repeated with similar results. We have demonstrated that Mazoferm E802, used alone for monitoring of B. invadens or in conjunction with spinosad for population suppression, shows great promise in Kenya.

  1. Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds

    OpenAIRE

    Mao, Shuqin; Wang, Kaidi; Lei, Yukun; Yao, Shuting; Lu, Baiyi; Huang, Weisu

    2017-01-01

    The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto?s model after the simulated digestion. T...

  2. Interactions in multispecies biofilms

    DEFF Research Database (Denmark)

    Burmølle, Mette; Ren, Dawei; Bjarnsholt, Thomas

    2014-01-01

    The recent focus on complex bacterial communities has led to the recognition of interactions across species boundaries. This is particularly pronounced in multispecies biofilms, where synergistic interactions impact the bacterial distribution and overall biomass produced. Importantly, in a number...... of settings, the interactions in a multispecies biofilm affect its overall function, physiology, or surroundings, by resulting in enhanced resistance, virulence, or degradation of pollutants, which is of significant importance to human health and activities. The underlying mechanisms causing these synergistic...

  3. Field evaluation of the efficacy and safety of a combination of spinosad and milbemycin oxime in the treatment and prevention of naturally acquired flea infestations and treatment of intestinal nematode infections in dogs in Europe.

    Science.gov (United States)

    Hayes, Brad; Schnitzler, Beate; Wiseman, Scott; Snyder, Daniel E

    2015-01-15

    Two separate randomised, blinded, multicentre field trials were conducted to evaluate the efficacy and safety of a combination of spinosad and milbemycin oxime (MO) (Trifexis(®), Elanco Animal Health) in the treatment and prevention of naturally acquired flea infestations and intestinal nematode infections in European dogs. Treatments using Trifexis(®) and each control veterinary product (CVP) were administered once on Day 0 in both field studies. In the flea field trial, 11 veterinary clinics in France participated in the study. On Day 0, whole body flea comb counts were conducted on all dogs being evaluated for enrolment. Dogs with ≥7 fleas on Day 0 were enrolled, treated once on Day 0 with spinosad/MO or the CVP (Stronghold(®); selamectin) and then underwent post-treatment flea counts on Days 14 and 30. There were 150 spinosad/MO treated dogs and 71 CVP treated dogs included in the flea effectiveness population. Effectiveness against fleas (% reduction in geometric means; GM) was 98.97% and 97.37% for the spinosad/MO treated dogs, and 97.43% and 93.96% for the CVP dogs on Days 14 and 30, respectively, compared to the pre-treatment baseline flea counts. Of the spinosad/MO dogs, 89.3% and 80.0% had no live fleas on Days 14 and 30, compared to 77.5% and 70.4% of the CVP dogs, respectively. In the nematode field trial, data from 10 veterinary clinics in France and 19 in Ireland were pooled. Faecal samples from dogs at each clinic were analysed. A positive result at screening (parasite eggs from Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum) allowed for enrolment. Dogs were randomised to spinosad/MO or the CVP (Milbemax(®); MO/praziquantel). On Day 8, a post-treatment faecal sample was taken and analysed. Of 2333 dogs screened for nematode eggs, 238 dogs were positive with one or more of these nematodes, and 229 were enrolled in the study. Of the 229 dogs, 151 were treated with a single dose of spinosad/MO, and 77 were treated with

  4. Synergistic combination dry powders for inhaled antimicrobial therapy

    Science.gov (United States)

    Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

    2013-06-01

    Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

  5. Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii.

    Science.gov (United States)

    Duarte, A; Ferreira, S; Silva, F; Domingues, F C

    2012-02-15

    In this study we investigated the existence of synergistic antibacterial effect between coriander (Coriandrum sativum L.) essential oil and six different antibacterial drugs (cefoperazone, chloramphenicol, ciprofloxacin, gentamicin, tetracycline and piperacillin). The antibacterial activity of coriander oil was assessed using microdilution susceptibility testing and synergistic interaction by checkerboard assays. The association of coriander essential oil with chloramphenicol, ciprofloxacin, gentamicin and tetracycline against Acinetobacter baumannii showed in vitro effectiveness, which is an indicator of a possible synergistic interaction against two reference strains of A. baumannii (LMG 1025 and LMG 1041) (FIC index from 0.047 to 0.375). However, when tested the involvement between coriander essential oil and piperacillin or cefoperazone, the isobolograms and FIC index showed an additive interaction. The in vitro interaction could improve the antimicrobial effectiveness of ciprofloxacin, gentamicin and tetracycline and may contribute to resensitize A. baumannii to the action of chloramphenicol. Copyright © 2011 Elsevier GmbH. All rights reserved.

  6. Silica ecosystem for synergistic biotransformation

    Science.gov (United States)

    Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

    2016-06-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system.

  7. Fatigue Resistant Bioinspired Composite from Synergistic Two-Dimensional Nanocomponents.

    Science.gov (United States)

    Wan, Sijie; Zhang, Qi; Zhou, Xiaohang; Li, Dechang; Ji, Baohua; Jiang, Lei; Cheng, Qunfeng

    2017-07-25

    Portable and wearable electronics require much more flexible graphene-based electrode with high fatigue life, which could repeatedly bend, fold, or stretch without sacrificing its mechanical properties and electrical conductivity. Herein, a kind of ultrahigh fatigue resistant graphene-based nanocomposite via tungsten disulfide (WS 2 ) nanosheets is synthesized by introducing a synergistic effect with covalently cross-linking inspired by the orderly layered structure and abundant interfacial interactions of nacre. The fatigue life of resultant graphene-based nanocomposites is more than one million times at the stress level of 270 MPa, and the electrical conductivity can be kept as high as 197.1 S/cm after 1.0 × 10 5 tensile testing cycles. These outstanding properties are attributed to the synergistic effect from lubrication of WS 2 nanosheets for deflecting crack propagation, and covalent bonding between adjacent GO nanosheets for bridging crack, which is verified by the molecular dynamics (MD) simulations. The WS 2 induced synergistic effect with covalent bonding offers a guidance for constructing graphene-based nanocomposites with high fatigue life, which have great potential for applications in flexible and wearable electronic devices, etc.

  8. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    Science.gov (United States)

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.Didecyldimethylammonium chloride [DDAC] was...

  9. Intrinsic synergistic-topological mechanism versus synergistic-topological matrix in microtubule self-organization

    Directory of Open Access Journals (Sweden)

    Buljan Vlado A

    2014-12-01

    Overall our data indicate that under crowded conditions in vitro, the self-organization of a microtubule fiber is governed by an intrinsic synergistic-topological mechanism, which in conjunction with the topological changes, GTP-tubulin depletion, and cooperative motion of fiber constituting microtubules, may generate and maintain a ‘synergistic-topological matrix’. Failure of the mechanism to form biologically feasible microtubule synergistic-topological matrix may, per se, precondition tumorigenesis.

  10. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Qiu, Peiju; Rakariyatham, Kanyasiri; Li, Fang; Gao, Zili; Cai, Xiaokun; Wang, Minqi; Xu, Fei; Zheng, Jinkai; Xiao, Hang

    2017-04-01

    Different cancer chemopreventive agents may act synergistically and their combination may produce enhanced protective effects against carcinogenesis than each individual agent alone. Herein, we investigated the chemopreventive effects of nobiletin (NBT, a citrus polymethoxyflavone) and atorvastatin (ATST, a lipid-lowering drug) in colon cancer cells/macrophages and an azoxymethane (AOM)-induced colon carcinogenesis rat model. The results demonstrated that co-treatments of NBT/ATST produced enhanced growth inhibitory and anti-inflammatory effects on the colon cancer cells and macrophages, respectively. Isobologram analysis confirmed that these interactions between NBT and ATST were synergistic. NBT/ATST co-treatment also synergistically induced extensive cell cycle arrest and apoptosis in colon cancer cells. Oral administration of NBT (0.1%, w/w in diet) or ATST (0.04%, w/w in diet) significantly decreased colonic tumor incidence and multiplicity in AOM-treated rats. Most importantly, co-treatment of NBT/ATST at their half doses (0.05% NBT + 0.02% ATST, w/w in diet) resulted in even stronger inhibitory effects on colonic tumor incidence and multiplicity than did NBT or ATST alone at higher doses. Statistical analysis confirmed that the enhanced chemopreventive activities against colon carcinogenesis in rats by the NBT/ATST combination were highly synergistic. Our results further demonstrated that NBT/ATST co-treatment profoundly modulated key cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis in the colon of AOM-treated rats. In conclusion, for the first time, our results demonstrated a strong synergy in inhibiting colon carcinogenesis produced by the co-treatment of NBT and ATST, which provided a scientific basis for using NBT in combination with ATST for colon cancer chemoprevention in humans. © The Author 2017. Published by Oxford University Press. All rights reserved

  11. Synergistic impacts of habitat loss and fragmentation on model ecosystems.

    Science.gov (United States)

    Bartlett, Lewis J; Newbold, Tim; Purves, Drew W; Tittensor, Derek P; Harfoot, Michael B J

    2016-09-28

    Habitat loss and fragmentation are major threats to biodiversity, yet separating their effects is challenging. We use a multi-trophic, trait-based, and spatially explicit general ecosystem model to examine the independent and synergistic effects of these processes on ecosystem structure. We manipulated habitat by removing plant biomass in varying spatial extents, intensities, and configurations. We found that emergent synergistic interactions of loss and fragmentation are major determinants of ecosystem response, including population declines and trophic pyramid shifts. Furthermore, trait-mediated interactions, such as a disproportionate sensitivity of large-sized organisms to fragmentation, produce significant effects in shaping responses. We also show that top-down regulation mitigates the effects of land use on plant biomass loss, suggesting that models lacking these interactions-including most carbon stock models-may not adequately capture land-use change impacts. Our results have important implications for understanding ecosystem responses to environmental change, and assessing the impacts of habitat fragmentation. © 2016 The Authors.

  12. The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture.

    Science.gov (United States)

    Del Rio, Beatriz; Redruello, Begoña; Linares, Daniel M; Ladero, Victor; Fernandez, Maria; Martin, Maria Cruz; Ruas-Madiedo, Patricia; Alvarez, Miguel A

    2017-03-01

    Tyramine and histamine are the biogenic amines (BA) most commonly found at high concentrations in food; they may even appear together at toxic concentrations. The present work examines, via real-time cell analysis, whether histamine and tyramine show synergistic toxicity towards intestinal cell cultures. Employing a constant equipotency ratio, their interaction was examined via the combination index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was associated with a stronger cytotoxic effect than was treatment with either BA or on its own. Indeed, a synergistic interaction (CIhistamine, at concentrations below the legal limit, increases the cytotoxicity of tyramine at concentrations frequently reached in some foods. The synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits designed to ensure consumer safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Human harvest, climate change and their synergistic effects drove the Chinese Crested Tern to the brink of extinction

    Directory of Open Access Journals (Sweden)

    Shuihua Chen

    2015-07-01

    Full Text Available Synergistic effect refers to simultaneous actions of separate factors which have a greater total effect than the sum of the individual factor effects. However, there has been a limited knowledge on how synergistic effects occur and individual roles of different drivers are not often considered. Therefore, it becomes quite challenging to manage multiple threatening processes simultaneously in order to mitigate biodiversity loss. In this regard, our hypothesis is, if the traits actually play different roles in the synergistic interaction, conservation efforts could be made more effectively. To understand the synergistic effect and test our hypothesis, we examined the processes associated with the endangerment of critically endangered Chinese Crested Tern (Thalasseus bernsteini, whose total population number was estimated no more than 50. Through monitoring of breeding colonies and investigations into causative factors, combined with other data on human activities, we found that widespread human harvest of seabird eggs and increasing frequency of typhoons are the major factors that threatened the Chinese Crested Tern. Furthermore, 28 percent of breeding failures were due to the synergistic effects in which egg harvest-induced renestings suffered the higher frequent typhoons. In such combined interactions, the egg harvest has clearly served as a proximal factor for the population decline, and the superimposition of enhanced typhoon activity further accelerated the species toward imminent extinction. Our findings suggest that species endangerment, on one hand, should be treated as a synergistic process, while conservation efforts, on the other hand, should focus principally on combatting the threat that triggers synergistic effects.

  14. Synergistic antitumor effects of novel HDAC inhibitors and paclitaxel in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Valentina Zuco

    Full Text Available Preclinical studies support the therapeutic potential of histone deacetylases inhibitors (HDACi in combination with taxanes. The efficacy of combination has been mainly ascribed to a cooperative effect on microtubule stabilization following tubulin acetylation. In the present study we investigated the effect of paclitaxel in combination with two novel HDACi, ST2782 or ST3595, able to induce p53 and tubulin hyperacetylation. A synergistic effect of the paclitaxel/ST2782 (or ST3595 combination was found in wild-type p53 ovarian carcinoma cells, but not in a p53 mutant subline, in spite of a marked tubulin acetylation. Such a synergistic interaction was confirmed in additional human solid tumor cell lines harboring wild-type p53 but not in those expressing mutant or null p53. In addition, a synergistic cytotoxic effect was found when ST2782 was combined with the depolymerising agent vinorelbine. In contrast to SAHA, which was substantially less effective in sensitizing cells to paclitaxel-induced apoptosis, ST2782 prevented up-regulation of p21(WAF1/Cip1 by paclitaxel, which has a protective role in response to taxanes, and caused p53 down-regulation, acetylation and mitochondrial localization of acetylated p53. The synergistic antitumor effects of the paclitaxel/ST3595 combination were confirmed in two tumor xenograft models. Our results support the relevance of p53 modulation as a major determinant of the synergistic interaction observed between paclitaxel and novel HDACi and emphasize the therapeutic interest of this combination.

  15. Synergistic effects of Chinese herbal medicine: a comprehensive review of methodology and current research

    Directory of Open Access Journals (Sweden)

    Xian Zhou

    2016-07-01

    Full Text Available Traditional Chinese medicine is an important part of primary health care in Asian countries that has utilised complex herbal formulations (consisting 2 or more medicinal herbs for treating diseases over thousands of years. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of Chinese herbal medicine, misconceptions about synergy, methodological challenges to study design. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. We discuss the strengthen and weakness of these models in the context of Chinese herbal medicine and summarise the current status of synergy research in CHM. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low and the clinical relevancy of most of these findings is undetermined. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations.

  16. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    2016-01-01

    dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat...... plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response...... surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response...

  17. Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols.

    Science.gov (United States)

    Seth, Kapileswar; Roy, Sudipta Raha; Pipaliya, Bhavin V; Chakraborti, Asit K

    2013-07-04

    Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.

  18. SYNERGISTIC ANTIBACTERIAL EFFECT OF STEM BARK ...

    African Journals Online (AJOL)

    userpc

    ABSTRACT. The study was aimed at screening the stem bark extracts of Faidherbia albida and Psidium guajava for synergistic antibacterial effect against methicillin resistant Staphylococcus aureus (MRSA). The powdered plant materials were extracted with methanol using cold maceration technique and the extracts were ...

  19. Modelling synergistic effects of appetite regulating hormones

    DEFF Research Database (Denmark)

    Schmidt, Julie Berg; Ritz, Christian

    2016-01-01

    We briefly reviewed one definition of dose addition, which is applicable within the framework of generalized linear models. We established how this definition of dose addition corresponds to effect addition in case only two doses per compound are considered for evaluating synergistic effects...

  20. Synergistic Antimicrobial Activities Of Phytoestrogens In Crude ...

    African Journals Online (AJOL)

    Ethanolic, methanolic and aqueous extracts of both leaves were studied for their in-vitro synergistic antimicrobial activity against both Gram positive and Gram negative micro-organisms, and Yeast using Agar diffusion method. The GC-MS phytochemical screening of methanolic extract showed that the major compounds in ...

  1. Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

    Directory of Open Access Journals (Sweden)

    Sinjan Choudhary

    Full Text Available We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

  2. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  3. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as ......The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...... also key figures in the philosophical discussions of nature and science - from philosophical tendencies like logical empiricism via critical rationalism to various neo-Kantian trends....

  4. Non-equilibrium synergistic effects in atmospheric pressure plasmas.

    Science.gov (United States)

    Guo, Heng; Zhang, Xiao-Ning; Chen, Jian; Li, He-Ping; Ostrikov, Kostya Ken

    2018-03-19

    Non-equilibrium is one of the important features of an atmospheric gas discharge plasma. It involves complicated physical-chemical processes and plays a key role in various actual plasma processing. In this report, a novel complete non-equilibrium model is developed to reveal the non-equilibrium synergistic effects for the atmospheric-pressure low-temperature plasmas (AP-LTPs). It combines a thermal-chemical non-equilibrium fluid model for the quasi-neutral plasma region and a simplified sheath model for the electrode sheath region. The free-burning argon arc is selected as a model system because both the electrical-thermal-chemical equilibrium and non-equilibrium regions are involved simultaneously in this arc plasma system. The modeling results indicate for the first time that it is the strong and synergistic interactions among the mass, momentum and energy transfer processes that determine the self-consistent non-equilibrium characteristics of the AP-LTPs. An energy transfer process related to the non-uniform spatial distributions of the electron-to-heavy-particle temperature ratio has also been discovered for the first time. It has a significant influence for self-consistently predicting the transition region between the "hot" and "cold" equilibrium regions of an AP-LTP system. The modeling results would provide an instructive guidance for predicting and possibly controlling the non-equilibrium particle-energy transportation process in various AP-LTPs in future.

  5. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...

  6. Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2011-01-01

    Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.

  7. Synergistic interactions between plant extracts, some antibiotics and ...

    African Journals Online (AJOL)

    user

    The methanol extraction ingredients recorded the maximum Inhibition Zone Diameter. (mm IZD); 18.8/R, 12.6/C and 12.8/G plants. Prominent synergism occurred between plants extract mixture and Gentamycin, Ceftasidine, Tobramycin, Cefoperazone and Spictinomycin (GD) antibiotics. Rehum plant extract was the most ...

  8. Synergistic Interactions of Neuroprotective and Neurotrophic Factors Against Sleep Deprivation

    Science.gov (United States)

    2017-03-30

    production exceeds cellular antioxidant defense capabilities, resulting in cellular damage due to oxidative modifications of proteins , lipids and nucleic...reticulum (ER) that are involved in the degradation of misfolded proteins in the brain isolated from several species (10). As stress can result in...translation, increased expression of molecular chaperones, enhancing degradation of misfolded proteins and restoring normal ER response critical for cell

  9. Synergistic effects in threshold models on networks

    Science.gov (United States)

    Juul, Jonas S.; Porter, Mason A.

    2018-01-01

    Network structure can have a significant impact on the propagation of diseases, memes, and information on social networks. Different types of spreading processes (and other dynamical processes) are affected by network architecture in different ways, and it is important to develop tractable models of spreading processes on networks to explore such issues. In this paper, we incorporate the idea of synergy into a two-state ("active" or "passive") threshold model of social influence on networks. Our model's update rule is deterministic, and the influence of each meme-carrying (i.e., active) neighbor can—depending on a parameter—either be enhanced or inhibited by an amount that depends on the number of active neighbors of a node. Such a synergistic system models social behavior in which the willingness to adopt either accelerates or saturates in a way that depends on the number of neighbors who have adopted that behavior. We illustrate that our model's synergy parameter has a crucial effect on system dynamics, as it determines whether degree-k nodes are possible or impossible to activate. We simulate synergistic meme spreading on both random-graph models and networks constructed from empirical data. Using a heterogeneous mean-field approximation, which we derive under the assumption that a network is locally tree-like, we are able to determine which synergy-parameter values allow degree-k nodes to be activated for many networks and for a broad family of synergistic models.

  10. Determining lower threshold concentrations for synergistic effects

    DEFF Research Database (Denmark)

    Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas

    2017-01-01

    which proven synergists cease to act as synergists towards the aquatic crustacean Daphnia magna. To do this, we compared several approaches and test-setups to evaluate which approach gives the most conservative estimate for the lower threshold for synergy for three known azole synergists. We focus.......619±8.555μgL(-1)) and 0.122±0.0417μM (40.236±13.75μgL(-1)), respectively, in the 14-days tests. Testing synergy in relation to concentration addition provided the most conservative values. The threshold values for the vertical assessments in tests where the two could be compared were in general 1.2 to 4.......7 fold higher than the horizontal assessments. Using passive dosing rather than dilution series or spiking did not lower the threshold significantly. Below the threshold for synergy, slight antagony could often be observed. This is most likely due to induction of enzymes active in metabolization of alpha...

  11. Assessment of owner-administered monthly treatments with oral spinosad or topical spot-on fipronil/(S)-methoprene in controlling fleas and associated pruritus in dogs.

    Science.gov (United States)

    Dryden, Michael W; Ryan, William G; Bell, Margie; Rumschlag, Anthony J; Young, Lisa M; Snyder, Daniel E

    2013-01-31

    Monitoring of the performance of flea control products under conditions of natural challenge is valuable in assessing continued effectiveness and determining the ongoing relevance of laboratory studies. A multi-clinic, investigator-blinded study was undertaken in client-owned dogs to investigate and compare the flea control provided by 3 consecutive monthly treatments of oral spinosad (SPN) or fipronil/(S)-methoprene topical (FSM) spot-on. The first household dog meeting enrollment criteria and with at least 10 fleas (whole-body flea count) served as the index dog in a household against which primary objectives were set. Stratification was based on pruritus scores at the enrollment visit and on single or multiple pet household. Index pets were randomized to treatment with either SPN or FSM, dispensed on day 0 for at-home administration by owners. All other household dogs and cats, maximum 4 pets per household, were dispensed the same treatment as the index dog (spinetoram was dispensed for cats in SPN households). Subsequent treatments were dispensed when index dogs were returned for whole-body flea counts and pruritus-scoring at visits on days 30 and 60, with final assessments on day 90 (±5 days on each occasion). Primary endpoints were the number of flea-free index dogs in each group one month after the final treatment, the reduction in owner-reported pruritus, and the reduction from baseline mean flea counts. One hundred twenty eight index dogs were enrolled (65 in the SPN arm; 63 in the FSM arm) at 10 clinics in FL (6), NC (2), LA (1), and TX (1). On day 0, geometric mean flea counts were 57.7 (range: 10-1469) and 44.8 (10-717) for the SPN and FSM groups, respectively. On Day 90, 55 of 58 (95%) and 21 of 55 (38%) index dogs completing the study were flea-free in SPN and FSM groups, respectively; mean SPN pruritus scores declined to 0.92 (6.67 on day 0), and to 3.83 (6.33 on day 0) for FSM; geometric mean flea counts (% control) were 0.08 (99.9%) and 5.19 (88

  12. Detecção e monitoramento da resistência do tripes Frankliniella occidentalis ao inseticida espinosade Detection and monitoring of resistance to the insecticide spinosad in the thrips Frankliniella occidentalis

    Directory of Open Access Journals (Sweden)

    Débora Soller Rais

    2013-01-01

    pests in greenhouses, especially on ornamental plants and vegetables. Among the problems faced by farmers are the difficulties in the control of this pest with the use of insecticides because of its preference for the inner parts of the flowers and the evolution of resistance to agrochemicals. The objective of this research was to characterize the spinosad resistance in F. occidentalis and to assess the frequency of resistant insects in commercial chrysanthemum fields from several counties in the state of São Paulo (SP. Selections for resistance to spinosad were performed under laboratory conditions, using a population of F. occidentalis collected in 2007 in a commercial chrysanthemum field in Campinas (SP. In the course of seven selections for resistance, the LC50 of spinosad increased from 8.41 mg a.i. L-1 to 1,111 mg a.i. L-1. Comparing the resistant (R and the susceptible (S strains, the resistance ratio (LC50 R / LC50 S reached values up to 280-folds. A discriminating concentration of 98 mg a.i. L-1 was established for monitoring the spinosad resistance in F. occidentalis. The survey was conducted by collecting 19 populations of thrips in commercial chrysanthemum fields in the state of São Paulo. The bioassays were conducted with second ínstar nymphs of F. occidentalis, placed in bean leaf disc arenas. The spinosad was sprayed at the discriminating concentration on the nymphs of thrips, using a Potter spray tower. The results indicated high variability in the susceptibility to spinosad among F. occidentalis populations. Populations with up to 40.7% of resistant insects were found. This is the first report on spinosad resistance in F. occidentalis in Brazil.

  13. Detecção e monitoramento da resistência do tripes Frankliniella occidentalis ao inseticida espinosade Detection and monitoring of resistance to the insecticide spinosad in the thrips Frankliniella occidentalis

    Directory of Open Access Journals (Sweden)

    Débora Soller Rais

    2013-03-01

    pests in greenhouses, especially on ornamental plants and vegetables. Among the problems faced by farmers are the difficulties in the control of this pest with the use of insecticides because of its preference for the inner parts of the flowers and the evolution of resistance to agrochemicals. The objective of this research was to characterize the spinosad resistance in F. occidentalis and to assess the frequency of resistant insects in commercial chrysanthemum fields from several counties in the state of São Paulo (SP. Selections for resistance to spinosad were performed under laboratory conditions, using a population of F. occidentalis collected in 2007 in a commercial chrysanthemum field in Campinas (SP. In the course of seven selections for resistance, the LC50 of spinosad increased from 8.41 mg a.i. L-1 to 1,111 mg a.i. L-1. Comparing the resistant (R and the susceptible (S strains, the resistance ratio (LC50 R / LC50 S reached values up to 280-folds. A discriminating concentration of 98 mg a.i. L-1 was established for monitoring the spinosad resistance in F. occidentalis. The survey was conducted by collecting 19 populations of thrips in commercial chrysanthemum fields in the state of São Paulo. The bioassays were conducted with second ínstar nymphs of F. occidentalis, placed in bean leaf disc arenas. The spinosad was sprayed at the discriminating concentration on the nymphs of thrips, using a Potter spray tower. The results indicated high variability in the susceptibility to spinosad among F. occidentalis populations. Populations with up to 40.7% of resistant insects were found. This is the first report on spinosad resistance in F. occidentalis in Brazil.

  14. Looming signals reveal synergistic principles of multisensory integration.

    Science.gov (United States)

    Cappe, Céline; Thelen, Antonia; Romei, Vincenzo; Thut, Gregor; Murray, Micah M

    2012-01-25

    Multisensory interactions are a fundamental feature of brain organization. Principles governing multisensory processing have been established by varying stimulus location, timing and efficacy independently. Determining whether and how such principles operate when stimuli vary dynamically in their perceived distance (as when looming/receding) provides an assay for synergy among the above principles and also means for linking multisensory interactions between rudimentary stimuli with higher-order signals used for communication and motor planning. Human participants indicated movement of looming or receding versus static stimuli that were visual, auditory, or multisensory combinations while 160-channel EEG was recorded. Multivariate EEG analyses and distributed source estimations were performed. Nonlinear interactions between looming signals were observed at early poststimulus latencies (∼75 ms) in analyses of voltage waveforms, global field power, and source estimations. These looming-specific interactions positively correlated with reaction time facilitation, providing direct links between neural and performance metrics of multisensory integration. Statistical analyses of source estimations identified looming-specific interactions within the right claustrum/insula extending inferiorly into the amygdala and also within the bilateral cuneus extending into the inferior and lateral occipital cortices. Multisensory effects common to all conditions, regardless of perceived distance and congruity, followed (∼115 ms) and manifested as faster transition between temporally stable brain networks (vs summed responses to unisensory conditions). We demonstrate the early-latency, synergistic interplay between existing principles of multisensory interactions. Such findings change the manner in which to model multisensory interactions at neural and behavioral/perceptual levels. We also provide neurophysiologic backing for the notion that looming signals receive preferential

  15. Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds

    Directory of Open Access Journals (Sweden)

    H. Hajimehdipoor

    2014-04-01

    Full Text Available Phenolic and flavonoid compounds are secondary metabolites of plants which possess various activities such as anti-inflammatory, analgesic, anti-diabetes and anticancer effects. It has been established that these compounds can scavenge free radicals produced in the body. Because of this ability, not only the plants containing phenolic and flavonoid compounds but also, the pure compounds are used in medicinal products for prevention and treatment of many disorders. Considering that the golden aim of the pharmaceutical industries is using the most effective compounds with lower concentrations, determination of the best combination of the compounds with synergistic effects is important. In the present study, synergistic antioxidant effects of four phenolic compounds including caffeic acid, gallic acid, rosmarinic acid, chlorogenic acid and two flavonoids,  rutin and quercetin, have been investigated by FRAP (Ferric Reducing Antioxidant Power method. The synergistic effect was assessed by comparing the experimental antioxidant activity of the mixtures with calculated theoretical values and the interactions of the compounds were determined. The results showed that combination of gallic acid and caffeic acid demonstrated considerable synergistic effects (137.8% while other combinations were less potent. Among examined substances, rutin was the only one which had no effect on the other compounds. The results of ternary combinations of compounds demonstrated antagonistic effects in some cases. This was more considerable in mixture of rutin, caffeic acid, rosmarinic acid (-21.8%, chlorogenic acid, caffeic acid, rosmarinic acid (-20%, rutin, rosmarinic acid, gallic acid (-18.5% and rutin, chlorogenic acid, caffeic acid (-15.8%, while, combination of quercetin, gallic acid, caffeic acid (59.4% and quercetin, gallic acid, rutin (55.2% showed the most synergistic effects. It was concluded that binary and ternary combination of quercetin, rutin, caffeic acid

  16. Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

    Directory of Open Access Journals (Sweden)

    Laura Bedin Denardi

    2015-03-01

    Full Text Available In vitro interaction between tacrolimus (FK506 and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%, followed by that of the combination with ketoconazole (37%, against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%, itraconazole (73%, voriconazole (63% and fluconazole (60%. The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

  17. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

    Science.gov (United States)

    Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

    2017-06-01

    Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

  18. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

    Directory of Open Access Journals (Sweden)

    Morgan A Wambaugh

    2017-06-01

    Full Text Available Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M. O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT. We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional

  19. White piedra: further evidence of a synergistic infection.

    Science.gov (United States)

    Youker, Summer R; Andreozzi, Robert J; Appelbaum, Peter C; Credito, Kim; Miller, Jeffrey J

    2003-10-01

    White piedra is a fungal infection of the hair shaft caused by Trichosporon beigelii. A synergistic coryneform bacterial infection is often present with T beigelii. White piedra, although not commonly reported to infect scalp hair in North America, is an important consideration in the differential diagnosis of scalp hair concretions. We report a case of white piedra of scalp hair with synergistic coryneform bacterial infection in two sisters, both US natives. Culture and light and electronmicroscopic evidence of the synergistic infection are presented.

  20. Mechanism of Synergistic Inhibition of Listeria monocytogenes Growth by Lactic Acid, Monolaurin, and Nisin▿

    OpenAIRE

    Tokarskyy, Oleksandr; Marshall, Douglas L.

    2008-01-01

    The combined lactic acid, monolaurin, and nisin effects on time-to-detection (optical density at 600 nm) extension were greater (P < 0.05) than any single or paired combination effect, which demonstrates a synergistic interaction among the antimicrobials. Monolaurin exposure caused C12:0 cell membrane incorporation. Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin had no influence. We postulate that lactic acid-enhanced monolaurin C12:0 incorporation into the ...

  1. Soy Phytochemicals and Tea Bioactive Components Synergistically Inhibit Androgen-Sensitive Human Prostate Tumors in Mice

    OpenAIRE

    Zhou, Jin-Rong; Yu, Lunyin; Zhong, Ying; Blackburn, George L.

    2003-01-01

    Although high doses of single bioactive agents may have potent anticancer effects, the chemopreventive properties of the Asian diet may result from interactions among several components that potentiate the activities of any single constituent. In Asia, where intake of soy products and tea consumption are very high, aggressive prostate cancer is significantly less prevalent in Asian men. The objective of the present study was to identify possible synergistic effects between soy and tea compone...

  2. Culture and neuroscience: additive or synergistic?

    Science.gov (United States)

    Dapretto, Mirella; Iacoboni, Marco

    2010-01-01

    The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings. PMID:20083533

  3. Synergistic drug combinations improve therapeutic selectivity

    Science.gov (United States)

    Lehàr, Joseph; Krueger, Andrew S.; Avery, William; Heilbut, Adrian M.; Johansen, Lisa M.; Price, E. Roydon; Rickles, Richard J.; Short, Glenn F.; Staunton, Jane E.; Jin, Xiaowei; Lee, Margaret S.; Zimmermann, Grant R.; Borisy, Alexis A.

    2009-01-01

    Prevailing drug discovery approaches focus on compounds with molecular selectivity, inhibiting disease-relevant targets over others in vitro. However in vivo, many such agents are not therapeutically selective, either because of undesirable activity at effective doses or because the biological system responds to compensate. In theory, drug combinations should permit increased control of such complex biology, but there is a common concern that therapeutic synergy will generally be mirrored by synergistic side-effects. Here we provide evidence, from 94,110 multi-dose combination experiments representing diverse disease areas and large scale flux balance simulations of inhibited bacterial metabolism, that multi-target synergies are more specific than single agent activities to particular cellular contexts. Using an anti-inflammatory combination, we show how multi-target synergy can achieve therapeutic selectivity in animals through differential target expression. Synergistic combinations can increase the number of selective therapies using the current pharmacopeia, and offer opportunities for more precise control of biological systems. PMID:19581876

  4. Hemolytic interactions of Dermatophilus congolensis.

    Science.gov (United States)

    Skalka, B; Pospísil, L

    1992-03-01

    The strains of Dermatophilus congolensis grew on blood agar with washed sheep erythrocytes with marked total hemolysis. In testing for hemolytic interactions they gave a significant synergistic effect of a characteristic shape with Rhodococcus equi and Streptococcus agalactiae, whereas with Staphylococcus aureus producing beta hemolysin and with Staphylococcus aureus producing delta hemolysin a simultaneous synergistic as well as antagonistic effect were observed. First of all a conspicuous inhibition of in the beta hemolysin zone began and then the hemolytic effect of D. congolensis was enhanced. A similar double reaction was also observed with Listeria ivanovii. With delta hemolysin there was an inhibition of the hemolytic effect of D. congolensis and at the same time a synergistic effect could be observed. Also D. congolensis gave a weak synergistic effect with Micrococcus lylae and Listeria monocytogenes, and a further weak antagonistic effect with alpha hemolysin of Staphylococcus aureus, Staphylococcus hyicus, Staphylococcus chromogenes and Micrococcus luteus. No interaction of D. congolensis was established with Corynebacterium pseudotuberculosis.

  5. Porphyromonas gingivalis and Treponema denticola synergistic polymicrobial biofilm development.

    Directory of Open Access Journals (Sweden)

    Ying Zhu

    Full Text Available Chronic periodontitis has a polymicrobial biofilm aetiology and interactions between key bacterial species are strongly implicated as contributing to disease progression. Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia have all been implicated as playing roles in disease progression. P. gingivalis cell-surface-located protease/adhesins, the gingipains, have been suggested to be involved in its interactions with several other bacterial species. The aims of this study were to determine polymicrobial biofilm formation by P. gingivalis, T. denticola and T. forsythia, as well as the role of P. gingivalis gingipains in biofilm formation by using a gingipain null triple mutant. To determine homotypic and polymicrobial biofilm formation a flow cell system was employed and the biofilms imaged and quantified by fluorescent in situ hybridization using DNA species-specific probes and confocal scanning laser microscopy imaging. Of the three species, only P. gingivalis and T. denticola formed mature, homotypic biofilms, and a strong synergy was observed between P. gingivalis and T. denticola in polymicrobial biofilm formation. This synergy was demonstrated by significant increases in biovolume, average biofilm thickness and maximum biofilm thickness of both species. In addition there was a morphological change of T. denticola in polymicrobial biofilms when compared with homotypic biofilms, suggesting reduced motility in homotypic biofilms. P. gingivalis gingipains were shown to play an essential role in synergistic polymicrobial biofilm formation with T. denticola.

  6. Porphyromonas gingivalis and Treponema denticola synergistic polymicrobial biofilm development.

    Science.gov (United States)

    Zhu, Ying; Dashper, Stuart G; Chen, Yu-Yen; Crawford, Simon; Slakeski, Nada; Reynolds, Eric C

    2013-01-01

    Chronic periodontitis has a polymicrobial biofilm aetiology and interactions between key bacterial species are strongly implicated as contributing to disease progression. Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia have all been implicated as playing roles in disease progression. P. gingivalis cell-surface-located protease/adhesins, the gingipains, have been suggested to be involved in its interactions with several other bacterial species. The aims of this study were to determine polymicrobial biofilm formation by P. gingivalis, T. denticola and T. forsythia, as well as the role of P. gingivalis gingipains in biofilm formation by using a gingipain null triple mutant. To determine homotypic and polymicrobial biofilm formation a flow cell system was employed and the biofilms imaged and quantified by fluorescent in situ hybridization using DNA species-specific probes and confocal scanning laser microscopy imaging. Of the three species, only P. gingivalis and T. denticola formed mature, homotypic biofilms, and a strong synergy was observed between P. gingivalis and T. denticola in polymicrobial biofilm formation. This synergy was demonstrated by significant increases in biovolume, average biofilm thickness and maximum biofilm thickness of both species. In addition there was a morphological change of T. denticola in polymicrobial biofilms when compared with homotypic biofilms, suggesting reduced motility in homotypic biofilms. P. gingivalis gingipains were shown to play an essential role in synergistic polymicrobial biofilm formation with T. denticola.

  7. Synergistic electrocatalytic effect of nanostructured mixed films formed by functionalised gold nanoparticles and bisphthalocyanines

    Energy Technology Data Exchange (ETDEWEB)

    Medina-Plaza, C. [Universidad de Valladolid, Department of Inorganic Chemistry, Engineers School (Spain); Furini, L.N. [Universidad de Valladolid, Department of Inorganic Chemistry, Engineers School (Spain); Faculdade de Ciências e Tecnologia, UNESP Univ Estadual Paulista, 19060-900 Presidente Prudente, SP (Brazil); Constantino, C.J.L. [Faculdade de Ciências e Tecnologia, UNESP Univ Estadual Paulista, 19060-900 Presidente Prudente, SP (Brazil); Saja, J.A. de [Universidad de Valladolid, Department of Condensed Matter Physics, Faculty of Sciences (Spain); Rodriguez-Mendez, M.L., E-mail: mluz@eii.uva.es [Universidad de Valladolid, Department of Inorganic Chemistry, Engineers School (Spain)

    2014-12-03

    Graphical abstract: Sensors based on gold nanoparticles and lutetium bisphthalocyanine, co-deposited using Langmuir–Blodgett technique, have demonstrated improved sensing properties towards hydroquinone due to synergistic effects. - Highlights: • Gold nanoparticles and lutetium bisphthalocyanine have been co-deposited using the LB technique. • Films used as voltammetric sensors provide enhanced responses towards hydroquinone. • The efficient electrocatalytic properties are due to synergistic effects. - Abstract: A synergistic electrocatalytic effect was observed in sensors where two electrocatalytic materials (functionalized gold nanoparticles and lutetium bisphthalocyanine) were co-deposited using the Langmuir–Blodgett technique. Films were prepared using a novel method where water soluble functionalised gold nanoparticles [(11-mercaptoundecyl)tetra(ethylene glycol)] (SAuNPs) were inserted in floating films of lutetium bisphthalocyanine (LuPc{sub 2}) and dimethyldioctadecylammonium bromide (DODAB) as the amphiphilic matrix. The formation of stable and homogeneous mixed films was confirmed by π-A isotherms, BAM, UV–vis and Raman spectroscopy, as well as by SEM and TEM microscopy. The synergistic effect towards hydroquinone of the electrodes modified with LuPc{sub 2}:DODAB/SAuNP was characterised by an increase in the intensity of the redox peaks and a reduction of the overpotential. This synergistic electrocatalytic effect arose from the interaction between the SAuNPs and the phthalocyanines that occur in the Langmuir–Blodgett films and from the high surface area provided by the nanostructured films. The sensitivity increased with the amount of LuPc{sub 2} and SAuNPs inserted in the films and limits of detection in the range of 10{sup −7} mol L{sup −1} were attained.

  8. Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells.

    Science.gov (United States)

    Maciejewski, Barbara A; Jamieson, Kyla C; Arnason, Jason W; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L; Leigh, Richard; Proud, David

    2017-05-01

    Exacerbations of chronic obstructive pulmonary disease are triggered by viral or bacterial pathogens, with human rhinovirus (HRV) and nontypeable Hemophilus influenzae (NTHI) among the most commonly detected pathogens. Patients who suffer from concomitant viral and bacterial infection have more severe exacerbations. The airway epithelial cell is the initial site of viral and bacterial interactions, and CCL20 is an epithelial chemokine that attracts immature dendritic cells to the airways and can act as an antimicrobial. As such, it contributes to innate and adaptive immune responses to infection. We used primary cultures of human bronchial epithelial cells and the BEAS-2B cell line to examine the effects of bacterial-viral coexposure, as well as each stimulus alone, on epithelial expression of CXCL8 and, in particular, CCL20. HRV-bacterial coexposure induced synergistic production of CXCL8 and CCL20 compared with the sum of each stimulus alone. Synergistic induction of CCL20 did not require viral replication and occurred with two different HRV serotypes that use different viral receptors. Synergy was also seen with either NTHI or Pseudomonas aeruginosa Synergistic induction of CCL20 was transcriptionally regulated. Although NF-κB was required for transcription, it did not regulate synergy, but NF-IL-6 did appear to contribute. Among MAPK inhibitors studied, neither SB203580 nor PD98059 had any effect on synergy, whereas U0126 prevented synergistic induction of CCL20 by HRV and bacteria, apparently via "off-target" effects. Thus bacterial-viral coexposure synergistically increases innate immune responses compared with individual infections. We speculate that this increased inflammatory response leads to worse clinical outcomes. Copyright © 2017 the American Physiological Society.

  9. Synergistic effect of eugenol with Colistin against clinical isolated Colistin-resistant Escherichia coli strains

    Directory of Open Access Journals (Sweden)

    Yi-ming Wang

    2018-01-01

    Full Text Available Abstract Background Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli strains, and to evaluate potential interaction. Methods Antimicrobial susceptibility, minimum inhibitory concentration (MIC and fractional inhibitory concentration index (FICI of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625. Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains. Graphical abstract Synergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.

  10. Obesity and bipolar disorder: synergistic neurotoxic effects?

    Science.gov (United States)

    Liu, Celina S; Carvalho, André F; Mansur, Rodrigo B; McIntyre, Roger S

    2013-11-01

    Bipolar disorder (BD) is a disabling and chronic neuropsychiatric disorder that is typified by a complex illness presentation, episode recurrence and by its frequent association with psychiatric and medical comorbidities. Over the past decade, obesity has emerged as one of many comorbidities generating substantial concern in the BD population due to important prognostic implications. This comprehensive review details the bidirectional relationship between obesity and BD as evidenced by alterations in the structure and function of the central nervous system, in addition to greater depressive recurrence, cognitive dysfunction and risk of suicidality. Drawing on current research results, this article presents several putative mechanisms underlying the synergistic toxic effects and provides a framework for future treatment options for the obesity-BD comorbidity. There is a need for more large-scale prospective studies to investigate the bidirectional relationships between obesity and BD.

  11. Synergistic effects of sodium lauroyl sarcosinate and glutamic acid in inhibition assembly against copper corrosion in acidic solution

    Science.gov (United States)

    Yu, Yinzhe; Zhang, Daquan; Zeng, Huijing; Xie, Bin; Gao, Lixin; Lin, Tong

    2015-11-01

    A self-assembled multilayer (SAM) from sodium lauroyl sarcosinate (SLS) and glutamic acid (GLU) is formed on copper surface. Its inhibition ability against copper corrosion is examined by electrochemical analysis and weight loss test. In comparison to SAM formed by just SLS or GLU, a synergistic effect is observed when the coexistence of SLS and GLU in SAM. The SLS/GLU SAM has an acicular multilayer structure, and SAM prepared under the condition of 5 mM SLS and 1 mM GLU shows the best protection efficiency. PM6 calculation reveals that the synergistic effect stems from interactions between SLS, GLU and cupric ions.

  12. Biomolecular Network-Based Synergistic Drug Combination Discovery

    Directory of Open Access Journals (Sweden)

    Xiangyi Li

    2016-01-01

    Full Text Available Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

  13. Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

    International Nuclear Information System (INIS)

    Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

    2014-01-01

    Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73

  14. Synergistic modulation by chloride and organic phosphates of hemoglobin from bear (Ursus arctos).

    Science.gov (United States)

    Coletta, M; Condo, S G; Scatena, R; Clementi, M E; Baroni, S; Sletten, S N; Brix, O; Giardina, B

    1994-03-11

    The oxygen binding properties of hemoglobin (Hb) from brown bear (Ursus arctos) have been studied focussing on the effect of heterotropic ligands, and the behaviour has been compared with that of human HbA, taken as a prototype of mammalian Hbs. It has been observed that in bear Hb chloride ions and 2,3-diphosphoglyceric acid (Gri(2,3)P2) can modulate the oxygen affinity in a synergistic way such that their individual effect is enhanced whenever they are both present in saturating amounts. The thermodynamic analysis of such a feature indicates that in bear Hb there are two classes of chloride binding sites, one acting synergistically with Gri(2,3)P2 and another one, which likely overlaps with the organic phosphate interaction cleft, and is therefore fully operative only in the absence of Gri(2,3)P2. The behaviour of the last site is similar to that observed in human HbA, where the effect of Cl- and Gri(2,3)P2 is mutually exclusive. The interaction energy between chloride and Gri(2,3)P2 synergistic binding sites appears to be O2-linked so that the interplay may have a relevant physiological role in modulating the oxygen transport in brown bear. This behaviour is associated with a marked pH-dependence of the oxygenation enthalpy in bear Hb, such that under acidotic and hypercloruremic conditions, oxygen supply to peripheral tissues could be maintained essentially unaltered even under low temperature conditions.

  15. Synergistic effects in radiation-induced particle ejection from solid surfaces

    International Nuclear Information System (INIS)

    Itoh, Noriaki

    1990-01-01

    A description is given on radiation-induced particle ejection from solid surfaces, emphasizing synergistic effects arising from multi-species particle irradiation and from irradiation under complex environments. First, it is pointed out that synergisms can be treated by introducing the effects of material modification on radiation-induced particle ejection. As examples of the effects of surface modification on the sputtering induced by elastic encounters, sputtering of alloys and chemical sputtering of graphite are briefly discussed. Then the particle ejection induced by electronic encounters is explained emphasizing the difference in the behaviors from materials to materials. The possible synergistic effects of electronic and elastic encounters are also described. Lastly, we point out the importance of understanding the elementary processes of material-particle interaction and of developing computer codes describing material behaviors under irradiation. (author)

  16. Synergistic activity of Bacillus thuringiensis toxins against Simulium spp. larvae.

    Science.gov (United States)

    Monnerat, Rose; Pereira, Eleny; Teles, Beatriz; Martins, Erica; Praça, Lilian; Queiroz, Paulo; Soberon, Mario; Bravo, Alejandra; Ramos, Felipe; Soares, Carlos Marcelo

    2014-09-01

    Species of Simulium spread diseases in humans and animals such as onchocerciasis and mansonelosis, causing health problems and economic loses. One alternative for controlling these insects is the use of Bacillus thuringiensis serovar israelensis (Bti). This bacterium produces different dipteran-active Cry and Cyt toxins and has been widely used in blackfly biological control programs worldwide. Studies on other insect targets have revealed the role of individual Cry and Cyt proteins in toxicity and demonstrated a synergistic effect among them. However, the insecticidal activity and interactions of these proteins against Simulium larvae have not been reported. In this study we demonstrate that Cry4Ba is the most effective toxin followed by Cry4Aa and Cry11Aa. Cry10Aa and Cyt1Aa were not toxic when administered alone but both were able to synergise the activity of Cry4B and Cry11Aa toxins. Cyt1Aa is also able to synergise with Cry4Aa. The mixture of all toxin-producing strains showed the greatest level of synergism, but still lower than the Bti parental strain. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Ocean warming and acidification synergistically increase coral mortality

    Science.gov (United States)

    Prada, F.; Caroselli, E.; Mengoli, S.; Brizi, L.; Fantazzini, P.; Capaccioni, B.; Pasquini, L.; Fabricius, K. E.; Dubinsky, Z.; Falini, G.; Goffredo, S.

    2017-01-01

    Organisms that accumulate calcium carbonate structures are particularly vulnerable to ocean warming (OW) and ocean acidification (OA), potentially reducing the socioeconomic benefits of ecosystems reliant on these taxa. Since rising atmospheric CO2 is responsible for global warming and increasing ocean acidity, to correctly predict how OW and OA will affect marine organisms, their possible interactive effects must be assessed. Here we investigate, in the field, the combined temperature (range: 16-26 °C) and acidification (range: pHTS 8.1-7.4) effects on mortality and growth of Mediterranean coral species transplanted, in different seasonal periods, along a natural pH gradient generated by a CO2 vent. We show a synergistic adverse effect on mortality rates (up to 60%), for solitary and colonial, symbiotic and asymbiotic corals, suggesting that high seawater temperatures may have increased their metabolic rates which, in conjunction with decreasing pH, could have led to rapid deterioration of cellular processes and performance. The net calcification rate of the symbiotic species was not affected by decreasing pH, regardless of temperature, while in the two asymbiotic species it was negatively affected by increasing acidification and temperature, suggesting that symbiotic corals may be more tolerant to increasing warming and acidifying conditions compared to asymbiotic ones.

  18. Synergistic Catalysis: A Powerful Synthetic Strategy for New Reaction Development

    Science.gov (United States)

    Allen, Anna E.; MacMillan, David W. C.

    2012-01-01

    Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature. PMID:22518271

  19. Synergistic Smart Fuel For Microstructure Mediated Measurements

    Energy Technology Data Exchange (ETDEWEB)

    James A. Smith; Dale K. Kotter; Steven L. Garrett; Randall A. Ali

    2013-07-01

    Advancing the Nuclear Fuel Cycle and Next Generation Nuclear Power Plants requires enhancing our basic understanding of fuel and materials behavior under irradiation. The two most significant issues limiting the effectiveness and lifespan of the fuel are the loss of thermal conductivity of the fuel and the mechanical strength of both fuel and cladding. The core of a nuclear reactor presents an extremely harsh and challenging environment for both sensors and telemetry due to elevated temperatures and large fluxes of energetic and ionizing particles from radioactive decay processes. The majority of measurements are made in reactors using “radiation hardened” sensors and materials. A different approach has been pursued in this research that exploits high temperatures and materials that are robust with respect to ionizing radiation. This synergistically designed thermoacoustic sensor will be self-powered, wireless, and provide telemetry. The novel sensor will be able to provide reactor process information even if external electrical power and communication are unavailable. In addition, the form-factor for the sensor is identical to the existing fuel rods within reactors and contains no moving parts. Results from initial proof of concept experiments designed to characterize porosity, surface properties and monitor gas composition will be discussed.

  20. Synergistic neurotrophic effects of piracetam and thiotriazoline

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available The paper considers the synergy between the nootropic drug piracetam and the metabolic agent thiotriazoline that maintains energy metabolism and survival of neurons and other types of cells. Piracetam, a nootropic drug, a chemical pyrrolidone derivative, is used in neurological, psychiatric, and narcological practice. There is evidence on the positive effect of piracetam in elderly and senile patients with coronary heart disease. This drug is supposed to stimulate redox processes, to enhance glucose utilization, and to improve regional blood flow in the ischemic brain regions. Due to its action, the drug activates glycolytic processes and elevates ATP concentrations in brain tissue. Thiotriazoline is a compound that has antioxidant, anti-ischemic properties. The co-administration of piracetam and thiothriazoline is an innovation area in the treatment of stroke and other brain damages, especially in insulin resistance and high blood glucose levels. The paper considers the neurobiological properties of thiotriazoline and piracetam, which synergistically exert neuroprotective and neurotrophic effects.

  1. Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

    Energy Technology Data Exchange (ETDEWEB)

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Crettaz, Pierre [Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); ETH Zürich, Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, Universitätsstrasse 16, CH-8092 Zürich (Switzerland)

    2014-09-15

    Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC{sub 25} and EC{sub 50}. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of

  2. Room temperature phosphorescence of five PAHs in a synergistic mesoporous silica nanoparticle-deoxycholate substrate

    Science.gov (United States)

    Qin, Jun; Li, Xiaomei; Feng, Feng; Pan, Qiliang; Bai, Yunfeng; Zhao, Jianguo

    2017-05-01

    A synergistic mesoporous silica nanoparticle-sodium deoxycholate (mPS-NaDC) substrate was developed for room temperature phosphorimetry. The synergistic substrate exhibited rapid and strong RTP-inducing ability against temperature variation. NaDC might adsorb on the inner surface of mPS pore by possible hydrogen bonding and protected the triplet state of polycyclic aromatic hydrocarbons (PAHs) with different molecular sizes. Two mPSs named LPMS1 and LPMS2 with pore size of 3.05 and 3.83 nm were synthesized and optimized in inducing RTP, and the latter, LPMS2, was selected as an ideal substrate because of its stronger protection ability to the triplet and good stability. Dibromopropane and cyclohexane were also used as assistant phosphorescence-inducers. All results demonstrated the feasibility and application potential of synergistic mPS-NaDC substrate in phosphorimetry. The interaction detail of NaDC and inner surface of selected mPS still needs to be explored in future.

  3. Synergistic antifungal activity of berberine derivative B-7b and fluconazole.

    Directory of Open Access Journals (Sweden)

    Li Ping Li

    Full Text Available Our previous study demonstrated berberine (BBR and fluconazole (FLC used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-ylethyl-2-(substituted phenylacet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells' self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections.

  4. Synergistic Adsorption and Flotation of New Mixed Cationic/Nonionic Collectors on Muscovite

    Directory of Open Access Journals (Sweden)

    Hao Jiang

    2017-05-01

    Full Text Available The mixed cationic collector cetyltrimethylammonium chloride (CTAC and nonionic collector octanol (OCT was found to exhibit a synergistic effect on the flotation and adsorption of muscovite. To understand the underlying synergistic mechanism, flotation, contact angle, surface tension, and adsorption measurements were carried out. The results obtained from flotation measurements indicated that the mixed CTAC/OCT exhibits a better collecting ability than CTAC or OCT. The recovery of muscovite with CTAC only rapidly decreased from 97.25% at pH 2.64 to 75.26% at pH 5.82, followed by a flat horizontal at a pH is higher than 6. In contrast, a high recovery of greater than 85% muscovite was observed using mixed CTAC/OCT at α CTAC = 0.67 (the mole ratio of CTAC:OCT = 2:1 over the investigated pH range. From the surface activity parameters (CMC, γ CMC, Γmax, Amin estimated from surface measurements and interaction parameters (βm, βσ, in addition to the micellar and interfacial compositions ( x 1 m , x 1 σ obtained from the theory of regular solutions, a synergistic effect is evident in the mixed micelle and at the water/air interface. Moreover, the mixed CTAC/OCT at α CTAC = 0.67 exhibited the maximum synergistic interaction. The results obtained from surface tension measurements indicated that the mixed CTAC/OCT exhibits considerably higher surface activities compared to single CTAC or OCT. The contact angle results confirmed that the mixed CTAC/OCT is a better collector than the individual CTAC or OCT for the flotation of muscovite. According to the results obtained from adsorption experiments, compared with that of individual CTAC or OCT, the amounts of CTAC and OCT adsorbed on the muscovite surface are considerably increase in the mixed systems because of co-adsorption. Based on these results, the mixed CTAC/OCT exhibits a remarkable synergistic effect during the flotation and adsorption of muscovite.

  5. Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses.

    Science.gov (United States)

    Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z

    2016-11-02

    Stress influences memory, an adaptive process crucial for survival. During stress, hippocampal synapses are bathed in a mixture of stress-released molecules, yet it is unknown whether or how these interact to mediate the effects of stress on memory. Here, we demonstrate novel synergistic actions of corticosterone and corticotropin-releasing hormone (CRH) on synaptic physiology and dendritic spine structure that mediate the profound effects of acute concurrent stresses on memory. Spatial memory in mice was impaired enduringly after acute concurrent stresses resulting from loss of synaptic potentiation associated with disrupted structure of synapse-bearing dendritic spines. Combined application of the stress hormones corticosterone and CRH recapitulated the physiological and structural defects provoked by acute stresses. Mechanistically, corticosterone and CRH, via their cognate receptors, acted synergistically on the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Accordingly, blocking the receptors of both hormones, but not each alone, rescued memory. Therefore, the synergistic actions of corticosterone and CRH at hippocampal synapses underlie memory impairments after concurrent and perhaps also single, severe acute stresses, with potential implications to spatial memory dysfunction in, for example, posttraumatic stress disorder. Stress influences memory, an adaptive process crucial for survival. During stress, adrenal corticosterone and hippocampal corticotropin-releasing hormone (CRH) permeate memory-forming hippocampal synapses, yet it is unknown whether (and how) these hormones interact to mediate effects of stress. Here, we demonstrate novel synergistic actions of corticosterone and CRH on hippocampal synaptic plasticity and spine structure that mediate the memory-disrupting effects of stress. Combined application of both hormones provoked synaptic function collapse and spine disruption

  6. Assessment of the Toxicity of Sub-chronic Low and High Doses of the Bio-insecticide Spinosad on the Liver, Kidney and the Cerebellum in Male Albino Mice

    Directory of Open Access Journals (Sweden)

    Sabry A El-Naggar

    2017-06-01

    Full Text Available ABSTRACT Spinosad (SPD is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1 served as a control, second group (G2 received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3 received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT, triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

  7. Synergistic effects of fire and elephants on arboreal animals in an African savanna.

    Science.gov (United States)

    Pringle, Robert M; Kimuyu, Duncan M; Sensenig, Ryan L; Palmer, Todd M; Riginos, Corinna; Veblen, Kari E; Young, Truman P

    2015-11-01

    Disturbance is a crucial determinant of animal abundance, distribution and community structure in many ecosystems, but the ways in which multiple disturbance types interact remain poorly understood. The effects of multiple-disturbance interactions can be additive, subadditive or super-additive (synergistic). Synergistic effects in particular can accelerate ecological change; thus, characterizing such synergies, the conditions under which they arise, and how long they persist has been identified as a major goal of ecology. We factorially manipulated two principal sources of disturbance in African savannas, fire and elephants, and measured their independent and interactive effects on the numerically dominant vertebrate (the arboreal gekkonid lizard Lygodactylus keniensis) and invertebrate (a guild of symbiotic Acacia ants) animal species in a semi-arid Kenyan savanna. Elephant exclusion alone (minus fire) had negligible effects on gecko density. Fire alone (minus elephants) had negligible effects on gecko density after 4 months, but increased gecko density twofold after 16 months, likely because the decay of fire-damaged woody biomass created refuges and nest sites for geckos. In the presence of elephants, fire increased gecko density nearly threefold within 4 months of the experimental burn; this occurred because fire increased the incidence of elephant damage to trees, which in turn improved microhabitat quality for geckos. However, this synergistic positive effect of fire and elephants attenuated over the ensuing year, such that only the main effect of fire was evident after 16 months. Fire also altered the structure of symbiotic plant-ant assemblages occupying the dominant tree species (Acacia drepanolobium); this influenced gecko habitat selection but did not explain the synergistic effect of fire and elephants. However, fire-driven shifts in plant-ant occupancy may have indirectly mediated this effect by increasing trees' susceptibility to elephant damage. Our

  8. Stroke from Vasospasm due to Marijuana Use: Can Cannabis Synergistically with Other Medications Trigger Cerebral Vasospasm?

    Directory of Open Access Journals (Sweden)

    Marium Jamil

    2016-01-01

    Full Text Available We present a case of imaging proven cerebral vasospasm causing ischemic stroke in a young patient chronically on buprenorphine-naloxone for heroin remission who started smoking cannabis on a daily basis. With cannabis legalization spreading across the states in the USA, it is important for physicians not only to be aware of cannabis reported association with cerebral vasospasm in some patients but also to be on the lookout for possible interacting medications that can synergistically affect cerebral vessels causing debilitating strokes.

  9. Lichenysin-geminal amino acid-based surfactants: Synergistic action of an unconventional antimicrobial mixture.

    Science.gov (United States)

    Coronel-León, Jonathan; Pinazo, Aurora; Pérez, Lourdes; Espuny, Mª José; Marqués, Ana Mª; Manresa, Angeles

    2017-01-01

    Recently it has been demonstrated that catanionic mixtures of oppositely charged surfactants have improved physicochemical-biological properties compared to the individual components. Isotherms of mixtures of an anionic biosurfactant (lichenysin) and a cationic aminoacid surfactant (C 3 (LA) 2 ) indicate a strong interaction suggesting the formation of a new "pseudo-surfactant". The antimicrobial properties of the mixture lichenysin and C 3 (LA) 2 M80:20, indicate a synergistic effect of the components. The mechanism of action on the bacterial envelope was assessed by flow cytometry and Transmission Electron Microscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Synergistic combinations of the CCR5 inhibitor VCH-286 with other classes of HIV-1 inhibitors.

    Science.gov (United States)

    Asin-Milan, Odalis; Sylla, Mohamed; El-Far, Mohamed; Belanger-Jasmin, Geneviève; Haidara, Alpha; Blackburn, Julie; Chamberland, Annie; Tremblay, Cécile L

    2014-12-01

    Here, we evaluated the in vitro anti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitors in vivo. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. COMBINATION OF MORPHINE AND GABAPENTIN LEADS TO SYNERGISTIC EFFECTS IN A RAT MODEL OF POSTOPERATIVE PAIN

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    Postoperative pain is a complex clinical condition that is still inadequately managed. Opioids remain the first line agents for the management of postoperative pain despite their side effects. Combination treatment with non-opioid agents that act at different sites within the central and peripheral...... of hindpaw withdrawal thresholds, after subcutaneous administration of morphine (0, 1, 3 and 7 mg/kg), gabapentin (0, 10, 30 and 100 mg/kg) or their combination (9 combinations of the above doses) were obtained using an electronic von Frey device. Surface of synergistic interaction (SSI) analysis was used...

  12. Synergistic estrogenic effects of Fusarium and Alternaria mycotoxins in vitro.

    Science.gov (United States)

    Vejdovszky, Katharina; Hahn, Kathrin; Braun, Dominik; Warth, Benedikt; Marko, Doris

    2017-03-01

    Mycotoxins are toxic secondary metabolites formed by various fungal species that are found as natural contaminants in food. This very heterogeneous group of compounds triggers multiple toxic mechanisms, including endocrine disruptive potential. Current risk assessment of mycotoxins, as for most chemical substances, is based on the effects of single compounds. However, concern on a potential enhancement of risks by interactions of single substances in naturally occurring mixtures has greatly increased recently. In this study, the combinatory effects of three mycoestrogens were investigated in detail. This includes the endocrine disruptors zearalenone (ZEN) and α-zearalenol (α-ZEL) produced by Fusarium fungi and alternariol (AOH), a cytotoxic and estrogenic mycotoxin formed by Alternaria species. For evaluation of effects, estrogen-dependent activation of alkaline phosphatase (AlP) and cell proliferation were tested in the adenocarcinoma cell line Ishikawa. The estrogenic potential varied among the single substances. Half maximum effect concentrations (EC50) for AlP activation were evaluated for α-ZEL, ZEN and AOH as 37 pM, 562 pM and 995 nM, respectively. All three mycotoxins were found to act as partial agonists. The majority of binary combinations, even at very low concentrations in the case of α-ZEL, showed strong synergism in the AlP assay. These potentiating phenomena of mycotoxin mixtures highlight the urgent need to incorporate combinatory effects into future risk assessment, especially when endocrine disruptors are involved. To the best of our knowledge, this study presents the first investigation on synergistic effects of mycoestrogens.

  13. Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant bacteria.

    Science.gov (United States)

    Hamoud, Razan; Reichling, Jürgen; Wink, Michael

    2015-02-01

    Drug combinations consisting of the DNA intercalating benzophenanthridine alkaloid sanguinarine, the chelator EDTA with the antibiotic streptomycin were tested against several Gram-positive and Gram-negative bacteria, including multi-resistant clinical isolates. Microdilution, checkerboard and time kill curve methods were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of combinations. Sanguinarine demonstrated a strong activity against Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations, MIC = 0.5-128 μg/ml), while streptomycin was active against Gram-negative strains (MIC = 2-128 μg/ml). EDTA showed only bacteriostatic activity. Indifference to synergistic activity was seen in the two-drug combinations sanguinarine + EDTA and sanguinarine + streptomycin (fractional inhibitory concentration index = 0.1-1.5), while the three-drug combination of sanguinarine + EDTA + streptomycin showed synergistic activity against almost all the strains (except methicillin-resistant Staphylococcus aureus), as well as a strong reduction in the effective doses (dose reduction index = 2-16 times) of sanguinarine, EDTA and streptomycin. In time kill studies, a substantial synergistic interaction of the three-drug combination was detected against Escherichia coli and Klebsiella pneumoniae. The combination of drugs, which interfere with different molecular targets, can be an important strategy to combat multidrug resistant bacteria. © 2014 Royal Pharmaceutical Society.

  14. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  15. Potent and Synergistic Extract Combinations from Terminalia Catappa, Terminalia Mantaly and Monodora tenuifolia Against Pathogenic Yeasts

    Science.gov (United States)

    Kammalac Ngouana, Thierry; Jiatsa Mbouna, Cedric Derick; Toghueo Kuipou, Rufin Marie; Tchuente Tchuenmogne, Marthe Aimée; Menkem Zeuko’o, Elisabeth; Ngouana, Vincent; Mallié, Michèle; Bertout, Sebastien; Boyom, Fabrice Fekam

    2015-01-01

    Mycoses caused by Candida and Cryptococcus species, associated with the advent of antifungal drug resistance have emerged as major health problems. Improved control measures and innovative therapies are needed. This paper describes results from the screening of bio-guided fractionated extracts alone and combinations of Terminalia catappa, Terminalia mantaly and Monodora tenuifolia harvested in Cameroon. Crude ethanolic, hydro-ethanolic and aqueous extracts and bio-guided fractions were screened for antifungal activity against isolates of C. albicans, C. glabrata, C. parapsilosis and Cr. neoformans and the reference strain C. albicans NR-29450. Minimal inhibitory concentrations (MIC) were determined using a broth micro dilution method according to the Clinical & Laboratory Standards Institute (CLSI). Time kill kinetics of extracts alone and in combination were also evaluated. Extracts from T. mantaly stem bark were the most active with the best MIC values ranging from 0.04 mg/mL to 0.16 mg/mL. Synergistic interactions were observed with combinations of sub-fractions from M. tenuifolia, T. mantaly and T. catappa. Combination of sub-fractions from M. tenuifolia and T. mantaly (C36/C12) showed synergistic interaction and fungicidal effect against four out of five tested yeasts. These results support further investigation of medicinal plant extracts alone and in combination as starting points for the development of alternative antifungal therapy. PMID:28930209

  16. Potent and Synergistic Extract Combinations from Terminalia Catappa, Terminalia Mantaly and Monodora tenuifolia Against Pathogenic Yeasts.

    Science.gov (United States)

    Ngouana, Thierry Kammalac; Mbouna, Cedric Derick Jiatsa; Kuipou, Rufin Marie Toghueo; Tchuenmogne, Marthe Aimée Tchuente; Zeuko'o, Elisabeth Menkem; Ngouana, Vincent; Mallié, Michèle; Bertout, Sebastien; Boyom, Fabrice Fekam

    2015-08-26

    Mycoses caused by Candida and Cryptococcus species, associated with the advent of antifungal drug resistance have emerged as major health problems. Improved control measures and innovative therapies are needed. This paper describes results from the screening of bio-guided fractionated extracts alone and combinations of Terminalia catappa, Terminalia mantaly and Monodora tenuifolia harvested in Cameroon. Crude ethanolic, hydro-ethanolic and aqueous extracts and bio-guided fractions were screened for antifungal activity against isolates of C. albicans , C. glabrata , C. parapsilosis and Cr. neoformans and the reference strain C. albicans NR-29450. Minimal inhibitory concentrations (MIC) were determined using a broth micro dilution method according to the Clinical & Laboratory Standards Institute (CLSI). Time kill kinetics of extracts alone and in combination were also evaluated. Extracts from T. mantaly stem bark were the most active with the best MIC values ranging from 0.04 mg/mL to 0.16 mg/mL. Synergistic interactions were observed with combinations of sub-fractions from M. tenuifolia , T. mantaly and T. catappa. Combination of sub-fractions from M. tenuifolia and T. mantaly (C36/C12) showed synergistic interaction and fungicidal effect against four out of five tested yeasts. These results support further investigation of medicinal plant extracts alone and in combination as starting points for the development of alternative antifungal therapy.

  17. Potent and Synergistic Extract Combinations from Terminalia Catappa, Terminalia Mantaly and Monodora tenuifolia Against Pathogenic Yeasts

    Directory of Open Access Journals (Sweden)

    Thierry Kammalac Ngouana

    2015-08-01

    Full Text Available Mycoses caused by Candida and Cryptococcus species, associated with the advent of antifungal drug resistance have emerged as major health problems. Improved control measures and innovative therapies are needed. This paper describes results from the screening of bio-guided fractionated extracts alone and combinations of Terminalia catappa, Terminalia mantaly and Monodora tenuifolia harvested in Cameroon. Crude ethanolic, hydro-ethanolic and aqueous extracts and bio-guided fractions were screened for antifungal activity against isolates of C. albicans, C. glabrata, C. parapsilosis and Cr. neoformans and the reference strain C. albicans NR-29450. Minimal inhibitory concentrations (MIC were determined using a broth micro dilution method according to the Clinical & Laboratory Standards Institute (CLSI. Time kill kinetics of extracts alone and in combination were also evaluated. Extracts from T. mantaly stem bark were the most active with the best MIC values ranging from 0.04 mg/mL to 0.16 mg/mL. Synergistic interactions were observed with combinations of sub-fractions from M. tenuifolia, T. mantaly and T. catappa. Combination of sub-fractions from M. tenuifolia and T. mantaly (C36/C12 showed synergistic interaction and fungicidal effect against four out of five tested yeasts. These results support further investigation of medicinal plant extracts alone and in combination as starting points for the development of alternative antifungal therapy.

  18. Ultrastrong Bioinspired Graphene-Based Fibers via Synergistic Toughening.

    Science.gov (United States)

    Zhang, Yuanyuan; Li, Yuchen; Ming, Peng; Zhang, Qi; Liu, Tianxi; Jiang, Lei; Cheng, Qunfeng

    2016-04-13

    Ultrastrong bioinspired graphene-based fibers are designed and prepared via synergistic toughening of ionic and covalent bonding. The tensile strength reaches up to 842.6 MPa and is superior to all other reported graphene-based fibers. In addition, its electrical conductivity is as high as 292.4 S cm(-1). This bioinspired synergistic toughening strategy supplies new insight toward the construction of integrated high-performance graphene-based fibers in the near future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synergistic energy conversion process using nuclear energy and fossil fuels

    International Nuclear Information System (INIS)

    Hori, Masao

    2007-01-01

    Because primary energies such as fossil fuels, nuclear energy and renewable energy are limited in quantity of supply, it is necessary to use available energies effectively for the increase of energy demand that is inevitable this century while keeping environment in good condition. For this purpose, an efficient synergistic energy conversion process using nuclear energy and fossil fuels together converted to energy carriers such are electricity, hydrogen, and synthetic fuels seems to be effective. Synergistic energy conversion processes containing nuclear energy were surveyed and effects of these processes on resource saving and the CO 2 emission reduction were discussed. (T.T.)

  20. Dental biofilm: ecological interactions in health and disease

    NARCIS (Netherlands)

    Marsh, P.D.; Zaura, E.

    Background: The oral microbiome is diverse and exists as multispecies microbial communities on oral surfaces in structurally and functionally organized biofilms. Aim: To describe the network of microbial interactions (both synergistic and antagonistic) occurring within these biofilms and assess

  1. Research on the relationship of institutional innovation, organizational learning and synergistic effect: An empirical study of chineses university spin-offs

    Directory of Open Access Journals (Sweden)

    Zhang Hao

    2014-06-01

    also as enterprise. This result of study pointed that. “Institutions” and “organizations” are the two important factors in synergistic innovation, so the synergy mechanism design should be followed by the interaction relationship between these two above. Originality/value: Synergistic innovation is the guidance theory which leads the development trend of university-industrial cooperation in China. In this paper, the "institution" and "organization", as the two primary elements, are introduced to analyze the process of synergistic innovation. Then, the authors discussed the role of the "institutional innovation" and "organizational learning" in the process of synergistic innovation, aimed at study on the operational mechanism of the influence factors.

  2. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

    2013-09-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

  3. Synergistic Anticancer Effects of Silibinin and Chrysin in T47D Breast Cancer Cells

    Science.gov (United States)

    Javan Maasomi, Zahra; Pilehvar Soltanahmadi, Younes; Dadashpour, Mehdi; Alipour, Shahriar; Abolhasani, Somayeh; Zarghami, Nosratollah

    2017-05-01

    Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was evaluated by MTT assay. Also, qRT-PCR was used to measure the expression levels of hTERT and cyclin D1 genes after 48 h treatment. Results: Cell viability assays revealed that chrysin or silibinin alone inhibited proliferation in a dose and time-dependent manner, and combining the drugs synergistically induced growth inhibition in the breast cancer cell line. The precise nature of this interaction was further analyzed by the median-effect method, where the combination indices (CI) were T47D cell proliferation. qPCR results showed that the drug combination also synergistically down-regulated the mRNA levels of hTERT and cyclin D1 at all used concentrations compared with the drugs used alone after 48 h treatment (P ≤ 0.05). Conclusion: The data provide evidence that synergistic antiproliferative effects of Chrysin and Silibinin are linked to the down-regulation of cyclin D1 and hTERT genes, and suggest that their combination may have therapeutic value in treatment of breast cancer. Creative Commons Attribution License

  4. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    International Nuclear Information System (INIS)

    Ricard, Clement; Fernandez, Manuel; Requardt, Herwig; Wion, Didier; Vial, Jean-Claude; Segebarth, Christoph; Sanden, Boudewijn van der

    2013-01-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion

  5. Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

    Science.gov (United States)

    Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

    2016-05-31

    Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT. Micro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups. We report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

  6. Mechanisms of synergistic skin penetration by sonophoresis and iontophoresis.

    Science.gov (United States)

    Hikima, Tomohiro; Ohsumi, Shinya; Shirouzu, Kenta; Tojo, Kakuji

    2009-05-01

    The mechanism of skin penetration enhancement by ultrasound under sonophoresis (US) or by an electrical field under iontophoresis (IP) was investigated using hairless mouse skin in vitro. The seven model chemicals with different molecular weights (122-1485) were dissolved in a hydrophilic gel. Donor gel with the chemicals was loaded on the skin surface and then the skin was treated with US (300 kHz, 5.2 W/cm(2), 5.4% duty-cycle) and IP (0.32+/-0.03 mA/cm(2)) individually or with US and IP in combination (US+IP). The penetration profiles of the chemicals with a molecular weight of less than 500 were influenced by the presence of an electric charge, the profiles of ionized chemicals for US+IP were the same as profiles for IP, while the penetration flux of a non-ionized chemical synergistically increased with US+IP compared with the individual flux of US and IP. The chemicals with molecular weight of more than 1000 showed synergistic effects with US+IP. The mathematical simulation assuming a bilayer skin model revealed that the synergistic effects were mainly influenced by electroosmosis in the stratum corneum (SC). Therefore the synergistic effects of US+IP was mainly caused by the SC diffusivity of chemicals increased by US and the electroosmotic water flow by IP application.

  7. Inhibitive and Synergistic Properties of Ethanolic Extract of ...

    African Journals Online (AJOL)

    It was also noted that only KCl was synergistic to the ethanol extract of Anogeissus leiocarpus, while other halides tested were antagonistic. All the data acquired reveal that the ethanolic extract of Anogeissus leiocarpus act as an inhibitor in the acid environment due to the phytochemicals: saponin, tannins, flavonoid, ...

  8. Synergistic Effect of Trehalose and Saccharose Pretreatment on ...

    African Journals Online (AJOL)

    2). Osmotic fragility is an important factor in the maintenance of RBC integrity and normal functions [23]. Trehalose and saccharose pretreatment synergistically decreased lyophilization-rehydration-induced damage on. RBC osmotic fragility by reducing the osmotic fragility (Fig. 3). PS is only distributed in the internal side of ...

  9. Synergistic therapy of enalapril and Cordyceps sinensis in the ...

    African Journals Online (AJOL)

    Chronic allograft nephropathy (CAN) still remains an important factor that affects the long-term survival of renal recipients. The aim of the study was to investigate synergistic effect of enalapril (an angiotensin converting enzyme inhibitor, ACEI) and Cordyceps sinensis (Bailing capsule, fermented agent of C. sinensis) on ...

  10. Synergistic Effect of Trehalose and Saccharose Pretreatment on ...

    African Journals Online (AJOL)

    Purpose: To investigate the synergistic effect of trehalose and saccharose pretreatment on maintenance of lyophilized human red blood cell (RBC) quality. Methods: RBCs were pre-treated with trehalose and saccharose, and then lyophilized and re-hydrated. Prior to lyophilization and after re hydration, RBC parameters, ...

  11. Synergistic antibacterial effect of stem bark extracts of Faidherbia ...

    African Journals Online (AJOL)

    The study was aimed at screening the stem bark extracts of Faidherbia albida and Psidium guajava for synergistic antibacterial effect against methicillin resistant Staphylococcus aureus (MRSA). The powdered plant materials were extracted with methanol using cold maceration technique and the extracts were screened for ...

  12. Hybrid Nanotechnologies for Detection and Synergistic Therapies for Breast Cancer

    Science.gov (United States)

    2012-10-01

    diagnostic nanosystems for therapeutic and theranostic targeting of breast cancers . 15. SUBJECT TERMS anti-angiogenesis, phage display, tumor homing...Therapies for Breast Cancer PRINCIPAL INVESTIGATOR: Erkki Ruoslahti, M.D., Ph.D...for Detection and Synergistic Therapies for Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-09-1-0698 5c. PROGRAM ELEMENT NUMBER

  13. Antioxidant, antimicrobial and synergistic activities of tea polyphenols

    African Journals Online (AJOL)

    Microbial resistance to antibiotics has become an increasing global problem and there is a need to find out novel potent antimicrobial agents with alternative modes of action as accessories to antibiotic therapy. This study investigated the antioxidant, antimicrobial and synergistic properties of tea polyphenols. The tea ...

  14. Synergistic effects of ethanolic plant extract mixtures against food ...

    African Journals Online (AJOL)

    Synergistic effects were observed when mixtures of ethanolic plant extract against food-borne pathogen bacteria were used, so this may be a better way to design alternative pathogen control methodologies for food-borne pathogen bacteria. Keywords: Larrea tridentate, Flourensia cernua, Opuntia ficus-indica, ethanolic ...

  15. Synergistic Effect of Poultry Manure and Sawdust on Changes in ...

    African Journals Online (AJOL)

    Synergistic Effect of Poultry Manure and Sawdust on Changes in Soil Structural Indices of a Sandy-Clay Loam Ultisol. ... Decreases in bulk density occurred as a result of increase in amendment applied, the trend was 8t>4t>2t for all the amendments. However, only the application of 8t/ha of poultry manure decrease bulk ...

  16. Synergistic effects of squalene and polyunsaturated fatty acid ...

    African Journals Online (AJOL)

    We have studied the synergistic effects of squalene and polyunsaturated fatty acids (PUFA concentrate) on isoprenaline-induced infarction in rats with respect to changes in the levels of plasma diagnostic marker enzymes and myocardial antioxidant defense system. Intraperitoneal injection of isoprenaline caused a ...

  17. Carbon dioxide and nisin act synergistically on Listeria monocytogenes

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Chen, Y.H.; Chikindas, M.L.

    2000-01-01

    This paper examines the synergistic action of carbon dioxide and nisin on Listeria monocytogenes Scott A wild-type and nisin-resistant (Nis(r)) cells grown in broth at 4 degrees C. Carbon dioxide extended the lag phase and decreased the specific growth rate of both strains, but to a greater degree...

  18. Synergistic extraction of thorium in presence of neutral donors

    International Nuclear Information System (INIS)

    Biswas, S.; Basu, S.

    1999-01-01

    The effects of neutral organophosphorous compounds on the extraction of thorium by β-hydroxy naphthaldoxime in xylene are reported. Enhancement of extraction is explained in terms of formation of a complex adduct in organic phase. Synergistic coefficients and apparent formation constants of complex adducts are calculated. (author)

  19. Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

  20. Synergistic effect of Murraya koenigii and Telfairia occidentalis ...

    African Journals Online (AJOL)

    Larger zones of inhibition were observed for M. Koenigii extract than T. occidentalis extract, and larger zones of inhibition were observed by their synergy than on their separate use. Synergistic antibacterial activity of the extract ranged from 0 mm to 20.0 ± 0.03 mm, zone of inhibition of M. koenigii extract ranged from 0 mm ...

  1. Tungstate as a synergist to phosphonate-based formulation for ...

    Indian Academy of Sciences (India)

    Administrator

    Tungstate as a synergist to phosphonate based formulation for corrosion control of carbon steel. 641. IEp (%) = 100 [1 – (i′corr/icorr)],. (2) where icorr and i′corr are the corrosion current densi- ties in case of the control and inhibitor solutions respectively. Impedance spectra in the form of Nyquist plots were recorded at ...

  2. Synergistic Activity of Methanolic Extract of Adenium obesum ...

    African Journals Online (AJOL)

    Synergistic Activity of Methanolic Extract of Adenium obesum (Apocynaceae) Stem-Bark and Oxytetracycline against Some Clinical Bacterial Isolates. ... Phytochemical examination of the extract revealed the presence of alkaloids, steroids, saponins, glycosides, anthraquinones, tannins and flavonoids. This result indicated ...

  3. Chemotherapeutic Impact Of Natural Antioxidant Flavonoids Gallic Acid Rutin Quercetin And Mannitol On Pathogenic Microbes And Their Synergistic Effect

    Directory of Open Access Journals (Sweden)

    Ganesh Ghosh

    2015-08-01

    Full Text Available Several studies suggest that natural flavonoids with antioxidants and can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents and Its prevalence over Multi drug resistant bacterial strain revived interest on Flavonoids. Synergistic effect is defined as passive interaction arises when two agents combine and together they exert an inhibitory effect that is greater than the sum of individual effect The new Synergistic therapy so that antioxidant are more effective in combination on multi drug resistant bacterial strain. Interaction between natural antioxidants and topoisomerase enzyme can be seen through Quercetin as a potent antimicrobial compound alone and in combination with other natural antioxidant like rutin. MICMBC result show antibacterial activity of the flavonoids were enhanced when used in combination against Staphylococcus aureus Bacillus cereus Bacillus subtilis Klebsiella pneumonae Escherichia coli as the test bacteria. The combination of rutin and quercetin rutin and gallic acid mannitol and gallic acid were much more effective than either flavonoid alone. Furthermore Its gave a good relation between these antioxidant compound and antimicrobial activity. Flavonoids as a chemotherapeutic agent and its Synergistic effect can be solution for various microbial disease conditions.

  4. In Vitro Synergistic Effect of Psidium guineense (Swartz in Combination with Antimicrobial Agents against Methicillin-Resistant Staphylococcus aureus Strains

    Directory of Open Access Journals (Sweden)

    Tiago Gomes Fernandes

    2012-01-01

    Full Text Available The aim of this study was to evaluate the antimicrobial activity of aqueous extract of Psidium guineense Swartz (Araçá-do-campo and five antimicrobials (ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, and meropenem against twelve strains of Staphylococcus aureus with a resistant phenotype previously determined by the disk diffusion method. Four S. aureus strains showed resistance to all antimicrobial agents tested and were selected for the study of the interaction between aqueous extract of P. guineense and antimicrobial agents, by the checkerboard method. The criteria used to evaluate the synergistic activity were defined by the fractional inhibitory concentration index (FICI. All S. aureus strains were susceptible to P. guineense as determined by the microdilution method. The combination of the P. guineense extract with the antimicrobial agents resulted in an eight-fold reduction in the MIC of these agents, which showed a FICI ranging from 0.125 to 0.5, suggesting a synergistic interaction against methicillin-resistant Staphylococcus aureus (MRSA strains. The combination of the aqueous extract of P. guineense with cefoxitin showed the lowest FICI values. This study demonstrated that the aqueous extract of P. guineense combined with beta lactamics antimicrobials, fluoroquinolones, and carbapenems, acts synergistically by inhibiting MRSA strains.

  5. ITK and ANALYZE: a synergistic integration

    Science.gov (United States)

    Augustine, Kurt E.; Holmes, David R., III; Robb, Richard A.

    2004-05-01

    The Insight Toolkit (ITK) is a C++ open-source software toolkit developed under sponsorship of the National Library of Medicine. It provides advanced algorithms for performing image registration and segmentation, but does not provide support for visualization and analysis, nor does it offer any graphical user interface (GUI). The purpose of this integration project is to make ITK readily accessible to end-users with little or no programming skills, and provide interactive processing, visualization and measurement capabilities. This is achieved through the integration of ITK with ANALYZE, a multi-dimension image visualization/analysis application installed in over 300 institutions around the world, with a user-base in excess of 4000. This integration is carried out at both the software foundation and GUI levels. The foundation technology upon which ANALYZE is built is a comprehensive C-function library called AVW. A new set of AVW-ITK functions have been developed and integrated into the AVW library, and four new ITK modules have been added to the ANALYZE interface. Since ITK is a software developer"s toolkit, the only way to access its intrinsic power is to write programs that incorporate it. Integrating ITK with ANALYZE opens the ITK algorithms to end-users who otherwise might never be able to take advantage of the toolkit"s advanced functionality. In addition, this integration provides end-to-end interactive problem solving capabilities which allow all users, including programmers, an integrated system to readily display and quantitatively evaluate the results from the segmentation and registration routines in ITK, regardless of the type or format of input images, which are comprehensively supported in ANALYZE.

  6. Synergistic effects of irradiation of waste-water

    International Nuclear Information System (INIS)

    Woodbridge, D.D.

    1975-01-01

    Water is an absolute necessity for all forms of animal and plant life. As man's requirements for water increase, the need for better methods of purification also increase. Technology has been slow to develop new methods of water treatment for the direct utilization of waste-water. Many new construction projects are at a standstill because waste-water treatment methods have not been developed to handle adequately the ever-increasing flow of sewage. Theoretical considerations of the use of high-level radiation in the treatment of waste-water have failed to consider the effects of the hydrated electron, and the potential of the possible synergistic effects of combining chlorine, oxygen and irradiation. An extensive testing programme at the University Center for Pollution Research of the Florida Institute of Technology over the past four years has shown that irradiation of waste-water samples immersed in an aqueous environment provide bacterial kill and reduction in organic pollution far greater than that obtained from theoretical considerations of G values and earlier experiments where the waste samples were not immersed in an aqueous environment. These testing programmes have investigated the synergistic effects of combining oxygen and irradiation. Each of these combined treatments resulted in an increased bacterial kill factor. Tests on Staphylococcus aureus bacteria and faecal streptococcus bacteria indicate that the synergistic effects observed for faecal coliform bacteria also apply to the pathogenic bacteria. A statistical analysis of the data obtained shows the relationships between the various effects on the bacteria. A definite shielding factor from the turbidity of the waste-water has been shown to exist. Synergistic effects have been shown to offset significantly the shielding effects. Optimization of these synergistic effects can greatly increase the effectiveness of irradiation in the treatment of waste-water. (author)

  7. Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

    NARCIS (Netherlands)

    Nijholt, W.; Jager-Wittenaar, H.; Visser, M.; Van der Schans, C. P.; Hobbelen, J. S. M.

    Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being

  8. Drug Repurposing Approach Identifies a Synergistic Drug Combination of an Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.

    Science.gov (United States)

    Riedel, Tina; Demaria, Olivier; Zava, Olivier; Joncic, Ana; Gilliet, Michel; Dyson, Paul J

    2018-01-02

    By screening a drug library comprising FDA approved compounds, we discovered a potent interaction between the antifungal agent haloprogin and the experimental organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The combination of these two small molecules, even at low doses, elicited an improved therapeutic response on tumor growth over either agent alone or the current treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma tumor model, where classical cytotoxic chemotherapeutic agents show little efficacy. The combination with the repurposed chemodrug haloprogin provides the basis for a new powerful treatment option for cutaneous melanoma. Importantly, because synergistic induction of tumor cell death is achieved with low individual drug doses, and cellular targets for RAPTA-T are different from those of classical chemotherapeutic drugs, a therapeutic strategy based on this approach could avoid toxicities and potentially resistance mechanisms, and could even inhibit metastatic progression.

  9. Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam.

    OpenAIRE

    Neu, H C

    1982-01-01

    The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam. beta-Lactamase-containing Escherichia coli resistant to mecillinam was synergistically inhibited by both clavulanic acid and sulbactam. beta-Lactamase-containing Enterobacter was synergistically inhibited, but strains lacking beta-lactamases were not synergistically inhibited. Synergistic inhibition was noted for beta-lactamase-containing, mecillinam-resistant Klebsiella, Citrobacter, Serratia, and Salm...

  10. Is the Combination of Insecticide and Mating Disruption Synergistic or Additive in Lightbrown Apple Moth, Epiphyas postvittana?

    Science.gov (United States)

    Suckling, David M; Baker, Greg; Salehi, Latif; Woods, Bill

    2016-01-01

    Pest suppression from combinations of tactics is fundamental to pest management and eradication. Interactions may occur among tactical combinations and affect suppression. The best case is synergistic, where suppression from a combination is greater than the sum of effects from single tactics (AB > A+B). We explored how mating disruption and insecticide interacted at field scale, additively or synergistically. Use of a pheromone delivery formulation (SPLAT™) as either a mating disruption treatment (i.e. a two-component pheromone alone) or as a lure and kill treatment (i.e. the two-component pheromone plus a permethrin insecticide) was compared for efficacy against the lightbrown apple moth Epiphyas postvittana. Next, four point-source densities of the SPLAT™ formulations were compared for communication disruption. Finally, the mating disruption and lure and kill treatments were applied with a broadcast insecticide. Population assessment used virgin female traps and synthetic pheromone in replicated 9-ha vineyard plots compared with untreated controls and insecticide-treated plots, to investigate interactions. Lure and kill and mating disruption provided equivalent suppression; no additional benefit accrued from including permethrin with the pheromone suggesting lack of contact. The highest point-source density tested (625/ha) was most effective. The insect growth regulator methoxyfenoxide applied by broadcast application lowered pest prevalence by 70% for the first ten weeks compared to pre-trial. Pheromone addition suppressed the pest further by an estimated 92.5%, for overall suppression of 97.7% from the treatment combination of insecticide plus mating disruption. This was close to that expected for an additive model of interactivity between insecticide and mating disruption (AB = A+B) estimated from plots with single tactics as 98% suppression in a combination. The results indicate the need to examine other tactical combinations to achieve the potential

  11. Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin.

    Science.gov (United States)

    Deters, M; Hütten, H; Kaever, V

    2013-01-15

    The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not-human cell lines. Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. To answer this question we investigated the interaction of both these substances on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation. OKT3-induced human PBMC proliferation was determined by measuring (3)H-thymidine incorporation. Influence of curcumin on interleukin-2 (IL-2) release and IκB-phosphorylation in PBMC was determined by ELISA and western blot, respectively. Curcumin-induced apoptosis and necrosis was analyzed by FACS analysis. Whereas curcumin completely inhibited OKT3-induced PBMC proliferation in a dose-dependent manner with an IC(50) of 2.8 μM, sirolimus could reduce PBMC proliferation dose-dependently only to a minimum of 28% at a concentration of 5 ng/ml (IC(50) 1.1 ng/ml). When curcumin was combined at concentrations of 1.25-2.5 μM with sirolimus at concentrations from 0.63 to 1.25 ng/ml the effects were synergistic. Combination of curcumin (1.25-2.5 μM) with sirolimus (5 ng/ml) showed additive effects. The effects after combination of curcumin at 5 μM with each sirolimus concentration and sirolimus at 10 ng/ml with each curcumin concentration were presumably antagonistic. We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3-activated PBMC. Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Synergistic Substrate and Oxygen Activation in Salicylate Dioxygenase Revealed by QM/MM Simulations.

    Science.gov (United States)

    Roy, Subhendu; Kästner, Johannes

    2016-01-18

    Salicylate 1,2-dioxygenase (SDO) is the first enzyme to be discovered to catalyze the oxidative cleavage of a monohydroxylated aromatic compound, namely salicylate, instead of the well-known electron-rich substrates. We have investigated the mechanism of dioxygen activation in SDO by QM/MM calculations. Our study reveals that the non-heme Fe(II) center in SDO activates salicylate and O2 synergistically through a strong covalent interaction to facilitate the reductive cleavage of O2. A covalent salicylate-Fe(II) -O2 complex is the reactive oxygen species in this case, and its electronic structure is best described as being between the two limiting cases, Fe(II)-O2 and Fe(II)-O2˙(-), with partial electron transfer from the activated salicylate to O2 via the Fe center. Thus SDO employs a synergistic strategy of substrate and oxygen activation to carry out the catalytic reaction, which is unprecedented in the family of iron dioxygenases. Moreover, O2 activation in SDO happens without the assistance of a proton source. Our study essentially shows a new mechanistic possibility for O2 activation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Characteristics and synergistic effects of co-pyrolysis of yinning coal and poplar sawdust

    Directory of Open Access Journals (Sweden)

    Zhu Shenghua

    2016-01-01

    Full Text Available Co-process of biomass and coal is perceived as a way to enhance the energy utilization by virtue of the integrated and interactive effects between different types of carbonaceous fuels. The purpose of this study was to investigate the co-pyrolysis characteristics of Yining coal and poplar sawdust, and to determine whether there is any synergistic effect in pyrolytic product yields. The coal was blended with sawdust at a mass fraction of 9:1, 7:3, 5:5, 3:7 and 1:9 respectively. The change of char yields, maximum weight loss rate and the corresponding temperature of different coal/sawdust blends during pyrolysis were compared by thermogravimetric analysis (TG. The total tar yields during separate coal, sawdust as well as their blends pyrolysis were acquired from the low temperature aluminum retort distillation test. By compare the experimental and theoretical value of the char yields from TG and tar yields from carbonization test, it was observed that co-pyrolysis of coal/sawdust blends produced less char and tar than the total amount produced by separate coal and sawdust pyrolysis. The different product distribution suggested that there was synergy effect in gas product yields. The co-pyrolysis of demineralized and devolatilized sawdust with coal indicated that the ash in the sawdust was the main contributor to the synergistic effect.

  14. The Goldilocks contract: The synergistic benefits of combining structure and autonomy for persistence, creativity, and cooperation.

    Science.gov (United States)

    Chou, Eileen Y; Halevy, Nir; Galinsky, Adam D; Murnighan, J Keith

    2017-09-01

    Contracts are commonly used to regulate a wide range of interactions and relationships. Yet relying on contracts as a mechanism of control often comes at a cost to motivation. Integrating theoretical perspectives from psychology, economics, and organizational theory, we explore this control-motivation dilemma inherent in contracts and present the Contract-Autonomy-Motivation-Performance-Structure (CAMPS) model, which highlights the synergistic benefits of combining structure and autonomy. The model proposes that subtle reductions in the specificity of a contract's language can boost autonomy, which increases intrinsic motivation and improves a range of desirable behaviors. Nine field and laboratory experiments found that less specific contracts increased task persistence, creativity, and cooperation, both immediately and longitudinally, because they boosted autonomy and intrinsic motivation. These positive effects, however, only occurred when contracts provided sufficient structure. Furthermore, the effects were limited to control-oriented clauses (i.e., legal clauses), and did not extend to coordination-oriented clauses (i.e., technical clauses). That is, there were synergistic benefits when a contract served as a scaffold that combined structure with general clauses. Overall, the current model and experiments identify a low-cost solution to the common problem of regulating social relationships: finding the right amount of contract specificity promotes desirable outcomes, including behaviors that are notoriously difficult to contract. The CAMPS model and the current set of empirical findings explain why, when, and how contracts can be used as an effective motivational tool. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. pH-responsive metallo-supramolecular nanogel for synergistic chemo-photodynamic therapy.

    Science.gov (United States)

    Yao, Xuemei; Chen, Li; Chen, Xiaofei; Xie, Zhigang; Ding, Jianxun; He, Chaoliang; Zhang, Jingping; Chen, Xuesi

    2015-10-01

    Benefited from the high orientation of coordinated interaction, metallo-supramolecular materials have attracted enormous interest in many fields. Herein, a novel metallo-supramolecular nanogel (SNG)-based drug delivery system for synergistic chemo-photodynamic therapy is explored to enhance anticancer efficacy. It is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. It can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells. Zn-Por moieties in SNG keep the photosensitivity in the range of visible wavelength and possess the ability of generating active oxygen species for photodynamic therapy. The drug-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy. Compared with the single chemotherapy of free doxorubicine (DOX) or photodynamic therapy of Zn-Por in SNG, DOX-loaded SNG with irradiation shows higher in vitro cytotoxicity and in vivo anticancer therapeutic activity, endowing the SNG with great potential in cancer treatments. A combination of multiple non-cross-resistant anticancer agents has been widely applied clinically. Applying multiple drugs with different molecular targets can raise the genetic barriers and delay the cancer adaption process. Multiple drugs targeting different cellular pathways can function synergistically, giving higher therapeutic efficacy and target selectivity. Overall, developing a combination therapeutic approach might even be the key to enhance anticancer efficacy and overcome chemo-resistance. Herein, a novel metallo-supramolecular nanogel (SNG) is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. The DOX-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy because it can respond to tumor acid microenvironment to release the co-delivered anticancer

  16. The identification and investigation of synergistic combinations of corrosion inhibitors for AA2024-T3

    Science.gov (United States)

    Chambers, Brian

    2007-12-01

    The overall goal of this research was to identify and investigate possible replacements of chromate corrosion inhibitive pigments for aluminum aerospace alloys. This research project was divided into two objectives: (1) to develop high throughput screening (HTS) methods that rapidly and quantitatively assess inhibitor and inhibitor mixture efficacy on aluminum alloy 2024-T3 (AA2024-T3) for the purpose of identifying synergies, and (2) to investigate the mechanisms of inhibitor interaction for a selected combination of compounds that demonstrate synergistic or antagonistic behavior. Thirteen inorganic compounds were selected from a review of the literature as promising candidates for AA2024-T3 inhibition or synergists with other inhibitors. These thirteen compounds, a large number of combinations, and sodium chromate were evaluated at 3.4 mM in 0.6 M NaCl to simulate the harsh conditions in which inhibitive pigments must perform. Three rapid test methods were developed and used to assess corrosion inhibitor performance on AA2024-T3: (1) the current at a fixed DC potential (100 mV) between two AA2024-T3 wire electrodes (50 parallel cells), (2) the cyclic voltammetric measurement of surface Cu following 24 hour open circuit (OC) exposure (96 parallel cells), and (3) the fluorometric measurement of aluminum ion concentration resulting from 24 hour OC corrosion (96 parallel cells). These methods were utilized to assess inhibitor performance on AA2024-T3 as a function of mixture ratio, pH, and concentration. A number of binary inhibitor mixtures demonstrated both potent and broad-range synergy as identified by the HTS methods. Two binary mixtures, cerium chloride with sodium metavanadate and lanthanum chloride with sodium molybdate, were selected for more detailed investigation due to their antagonistic and synergistic interaction respectively. Experimental evidence supports the hypothesis that the antagonistic interaction between cerium and metavanadate originates from

  17. The coordination structure of the extracted copper(II) complex with a synergistic mixture containing dinonylnaphthalene sulfonic acid and n-hexyl 3-pyridinecarboxylate ester

    Science.gov (United States)

    Zhu, Shan; Hu, Huiping; Hu, Jiugang; Li, Jiyuan; Hu, Fang; Wang, Yongxi

    2017-09-01

    In continuation of our interest in the coordination structure of the nickel(II) complex with dinonylnaphthalene sulfonic acid (HDNNS) and 2-ethylhexyl 4-pyridinecarboxylate ester (4PC), it was observed that the coordination sphere was completed by the coordination of two N atoms of pyridine rings in ligands 4PC and four water molecules while no direct interaction between Ni(II) and deprotonated HDNNS was observed. To investigate whether the coordination structure of nickel(II) with the synergistic mixture containing HDNNS and 4PC predominates or not in the copper(II) complex with the synergistic mixtures containing HDNNS and pyridinecarboxylate esters, a copper(II) synergist complex with n-hexyl 3-pyridinecarboxylate ester (L) and naphthalene-2-sulfonic acid (HNS, the short chain analogue of HDNNS), was prepared and studied by X-ray single crystal diffraction, elemental analyses and thermo gravimetric analysis (TGA), respectively. It was shown that the composition of the copper(II) synergist complex was [Cu(H2O)2(L)2(NS)2] and formed a trans-form distorted octahedral coordination structure. Two oxygen atoms of the two coordinated water molecules and two N atoms of the pyridine rings in the ligands L defined the basal plane while two O atoms from two sulfonate anions of the deprotonated HNS ligands occupied the apical positions by direct coordination with Cu(II), which was distinguished from the coordination structure of the nickel(II) synergist complex as reported in our previous work. In the crystal lattice, neighboring molecules [Cu(H2O)2L2(NS)2] were linked through the intermolecular hydrogen bonds between the hydrogen atoms of the coordinated water molecules and the oxygen atoms of the sulfonate anions in the copper(II) synergist complex to form a 2D plane. In order to bridge the gap between the solid state structure of the copper(II) synergist complex and the solution structure of the extracted copper(II) complex with the actual synergistic mixture containing

  18. Synergistic antibiotic combinations for colistin-resistant Klebsiella pneumoniae.

    Science.gov (United States)

    Kádár, Béla; Kocsis, Béla; Tóth, Ákos; Damjanova, Ivelina; Szász, Máté; Kristóf, Katalin; Nagy, Károly; Szabó, Dóra

    2013-06-01

    In this study antibiotic combinations for multidrug-resistant Klebsiella pneumoniae strains were investigated. The study included a colistin-susceptible and a colistin-resistant KPC-2 producing K. pneumoniae ST258 strains isolated in 2008 and 2009 during an outbreak in Hungary. Antibiotic combinations were analyzed by checkerboard technique and fractional inhibitory concentration indices were calculated. The following antibiotics were tested: ceftazidime, cefotaxime, ceftriaxone, ampicillin, imipenem, ertapenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, polymyxin B and colistin. Combinations including 0.25 μg/ml colistin plus 1 μg/ml rifampicin, 0.25 μg/ml polymyxin B plus 1 μg/ml rifampicin, 1 μg/ml imipenem plus 2 μg/ml tobramycin, were found synergistic.These in vitro synergistic combinations suggest potential therapeutical options against infections caused by KPC-2 producing, multidrug-resistant K. pneumoniae ST258.

  19. Comprehension of synergistic mechanisms for uranium extraction from phosphate ores

    International Nuclear Information System (INIS)

    Pecheur, Olivia

    2014-01-01

    Uranium VI is commonly extracted from phosphoric ores by a well-known process exploiting the synergistic mixture of two extractant molecules: HDEHP and TOPO. In the field of liquid-liquid extraction, synergistic combinations are common but the mechanisms at the origin of the synergy are not well understood. A multi-scale approach has been used to describe these mechanisms, combining two different descriptions: the molecular scale focuses on the ion point of view, while the supramolecular scale focuses on extractants' aggregation. These two approaches have been rationalized by molecular dynamics computations. The results allow describing the synergy through the structure of the complexes and aggregates. With the same approach, some bifunctional compounds, combining the two extracting sites in one molecule, have been studied and compared to the HDEHP/TOPO system in order to identify the origin of their increased capacities in extraction and selectivity. (author) [fr

  20. Effects of immune synergist of Chinese medicinal herbs on the ...

    African Journals Online (AJOL)

    AJL

    2012-01-19

    Jan 19, 2012 ... Two-month-old piglets were fed with 1, 1.5 and 2% immune synergist of Chinese medicinal herbs together with vaccination against classic swine fever. Serum IgG and IgM levels increased more than the control group on day. 30 (P<0.05). B and T lymphocyte proliferation in piglets fed with 1.5 and 2% ...

  1. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity

    Science.gov (United States)

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L.; Avery, Simon V.

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  2. Synergistic Antimicrobial Effect of Tribulus terrestris and Bitter Almond Extracts

    Directory of Open Access Journals (Sweden)

    Hamid Abtahi

    2014-12-01

    Full Text Available Background: The antimicrobial effects of the extracts of different kinds of plants have been demonstrated in several studies. However, no study has been conducted so far on the synergistic effects of two herbal extracts on their germicidal effects. In this study, in addition to antibacterial effects of the aqueous, methanol or ethanol extracts of Tribulus terrestris and bitter almond on some bacteria, the synergistic effects of the extracts of these two plants were also evaluated. Materials and Methods: In this experimental study, water, methanol and ethanol extracts of seeds were screened against some bacterial strains. Seeds were extracted by percolation method. Aliquots of the extracts at variable concentrations were then incubated with different bacterial strains, and the antimicrobial activities of the extracts from seeds were determined by MIC. Three antibiotics were used as reference compounds for antibacterial activities. Seeds extract inhibited significantly the growth of the tested bacterial strains. Results: The greatest synergistic effect of T. terrestris and bitter almond extracts is detected in methanol and aqueous extracts. Among the bacterial strains tested, Staphylococcus aureus was most susceptibility. Conclusion: The results showed the highest antibacterial effect in the combination of methanol extract of T. terrestris and the aqueous extract of the bitter almond.

  3. A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability.

    Science.gov (United States)

    Septama, Abdi Wira; Xiao, Jianbo; Panichayupakaranant, Pharkphoom

    2017-01-01

    Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Escherichia coli . A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis. Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA.

  4. Synergistic mortality between a neonicotinoid insecticide and an ergosterol-biosynthesis-inhibiting fungicide in three bee species.

    Science.gov (United States)

    Sgolastra, Fabio; Medrzycki, Piotr; Bortolotti, Laura; Renzi, Maria Teresa; Tosi, Simone; Bogo, Gherardo; Teper, Dariusz; Porrini, Claudio; Molowny-Horas, Roberto; Bosch, Jordi

    2017-06-01

    Neonicotinoid insecticides have been identified as an important factor contributing to bee diversity declines. Nonetheless, uncertainties remain about their impact under field conditions. Most studies have been conducted on Apis mellifera and tested single compounds. However, in agricultural environments, bees are often exposed to multiple pesticides. We explore the synergistic mortality between a neonicotinoid (clothianidin) and an ergosterol-biosynthesis-inhibiting fungicide (propiconazole) in three bee species (A. mellifera, Bombus terrestris, Osmia bicornis) following oral exposure in the laboratory. We developed a new approach based on the binomial proportion test to analyse synergistic interactions. We estimated uptake of clothianidin per foraging bout in honey bees foraging on seed-coated rapeseed fields. We found significant synergistic mortality in all three bee species exposed to non-lethal doses of propiconazole and their respective LD 10 of clothianidin. Significant synergism was only found at the first assessment times in A. mellifera (4 and 24 h) and B. terrestris (4 h), but persisted throughout the experiment (96 h) in O. bicornis. O. bicornis was also the most sensitive species to clothianidin. Our results underscore the importance to test pesticide combinations likely to occur in agricultural environments, and to include several bee species in environmental risk assessment schemes. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  5. Thermodynamic Description of Synergy in Solvent Extraction: II Thermodynamic Balance of Driving Forces Implied in Synergistic Extraction.

    Science.gov (United States)

    Rey, J; Bley, M; Dufrêche, J-F; Gourdin, S; Pellet-Rostaing, S; Zemb, T; Dourdain, S

    2017-11-21

    In the second part of this study, we analyze the free energy of transfer in the case of synergistic solvent extraction. This free energy of the transfer of an ion in dynamic equilibrium between two coexisting phases is decomposed into four driving forces combining long-range interactions with the classical complexation free energy associated with the nearest neighbors. We demonstrate how the organometallic complexation is counterbalanced by the cost in free energy related to structural change on the colloidal scale in the solvent phase. These molecular forces of synergistic extraction are driven not only by the entropic term associated with the tight packing of electrolytes in the solvent and by the free energy cost of coextracting water toward the hydrophilic core of the reverse aggregates present but also by the entropic costs in the formation of the reverse aggregate and by the interfacial bending energy of the extractant molecules packed around the extracted species. Considering the sum of the terms, we can rationalize the synergy observed, which cannot be explained by classical extraction modeling. We show an industrial synergistic mixture combining an amide and a phosphate complexing site, where the most efficient/selective mixture is observed for a minimal bending energy and maximal complexation energy.

  6. Synergistic combinations of five single drugs from Centella asiatica for neuronal differentiation.

    Science.gov (United States)

    Lin, Jinjin; Jiang, Hui; Ding, Xianting

    2017-01-01

    To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

  7. Epidemiology and Synergistic Hepatopathology of Malaria and Hepatitis C Virus Coinfection.

    Science.gov (United States)

    Nasir, Idris Abdullahi; Yakubu, Sa'adatu; Mustapha, Jelili Olaide

    2017-01-01

    Malaria and hepatitis C virus (HCV) infections are very common causes of human suffering with overlapping global geographic distributions. With the growing incidence of HCV infections in malaria-endemic zones and malaria in areas with exceptionally high HCV prevalence, coinfections and syndemism of both pathogens are likely to occur. However, studies of malaria and HCV coinfections are very rare despite the fact that liver-stage plasmodiasis and hepatitis C develop in hepatocytes which may synergistically interact. The fact that both pathogens share similar entry molecules or receptors in early invasive steps of hepatocytes further makes hepatopathologic investigations of coinfected hosts greatly important. This review sought to emphasize the public health significance of malaria/HCV coinfections and elucidate the mechanisms of pathogens' entrance and invasion of susceptible host to improve on existing or develop antiplasmodial drugs and hepatitis C therapeutics that can intervene at appropriate stages of pathogens' life cycles.

  8. Synergistic Effect of Copper and Cobalt in Cu-Co-O Composite Nanocatalyst for Catalytic Ozonation

    International Nuclear Information System (INIS)

    Dong, Yuming; Wu, Lina; Wang, Guangli; Zhao, Hui; Jiang, Pingping; Feng, Cuiyun

    2013-01-01

    A novel Cu-Co-O composite nanocatalyst was designed and prepared for the ozonation of phenol. A synergistic effect of copper and cobalt was observed over the Cu-Co-O composite nanocatalyst, which showed higher activity than either copper or cobalt oxide alone. In addition, the Cu-Co-O composite revealed good activity in a wide initial pH range (4.11-8.05) of water. The fine dispersion of cobalt on the surface of copper oxide boosted the interaction between catalyst and ozone, and the surface Lewis acid sites on the Cu-Co-O composite were determined as the active sites. The Raman spectroscopy also proved that the Cu-Co-O composite was quite sensitive to the ozone. The trivalent cobalt in the Cu-Co-O composite was proposed as the valid state

  9. High residue contents indebted by platinum and silica synergistic action during the pyrolysis of silicone formulations.

    Science.gov (United States)

    Delebecq, Etienne; Hamdani-Devarennes, Siska; Raeke, Julia; Lopez Cuesta, José-Marie; Ganachaud, François

    2011-03-01

    The synergistic role of platinum and silica as a way to increase the final residue of pyrolized silicone was investigated and explained, giving new interpretations. Conditions were first set to study the thermal degradation of silicones in the presence of platinum based on the simplest silicone/silica/platinum formulation. Numerous parameters, e.g., platinum and silica content or silica surface modifications, were varied to track their influences on the final residues. A thorough DSC study, together with SEM/EDX and Pyrolysis/GC-MS analyses, led us to propose a three-stage process. The key parameter governing thermal stability and final content of the residue is the conjugated actions of immobilizing/cross-linking PDMS chains. Silica particles tether silicone chains through physical interactions, i.e., hydrogen bonding, facilitating a platinum radically catalyzed cross-linking reaction. Practical implications and possible improvements on LSR formulations are finally given.

  10. Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination

    Science.gov (United States)

    Bag, Anwesa; Chattopadhyay, Rabi Ranjan

    2015-01-01

    The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf), cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium) using microbroth dilution, checkerboard titration and time-kill methods. Antioxidant combination effect was assessed by DPPH free radical scavenging method. Total phenolic content was measured by Folin-Ciocalteu method. Bioactivity –guided fractionation of active essential oils for isolation of bioactive compounds was done using TLC-bioautography assay and chemical characterization (qualitative and quantitative) of bioactive compounds was performed using DART-MS and HPLC analyses. Cytotoxic potential was evaluated by brine shrimp lethality assay as well as MTT assay using human normal colon cell line. Results showed that among the possible combinations tested only coriander/cumin seed oil combination showed synergistic interactions both in antibacterial (FICI : 0.25-0.50) and antioxidant (CI : 0.79) activities. A high positive correlation between total phenolic content and antibacterial activity against most of the studied bacteria (R2 = 0.688 – 0.917) as well as antioxidant capacity (R2 = 0.828) was also observed. TLC-bioautography-guided screening and subsequent combination studies revealed that two compounds corresponding to Rf values 0.35 from coriander seed oil and 0.53 from cumin seed oil exhibited both synergistic antibacterial and antioxidant activities. The bioactive compound corresponding to Rf 0.35 from coriander seed oil was identified as linalool (68.69%) and the bioactive compound corresponding to Rf 0.53 from cumin seed oil was identified

  11. Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination.

    Directory of Open Access Journals (Sweden)

    Anwesa Bag

    Full Text Available The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf, cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium using microbroth dilution, checkerboard titration and time-kill methods. Antioxidant combination effect was assessed by DPPH free radical scavenging method. Total phenolic content was measured by Folin-Ciocalteu method. Bioactivity -guided fractionation of active essential oils for isolation of bioactive compounds was done using TLC-bioautography assay and chemical characterization (qualitative and quantitative of bioactive compounds was performed using DART-MS and HPLC analyses. Cytotoxic potential was evaluated by brine shrimp lethality assay as well as MTT assay using human normal colon cell line. Results showed that among the possible combinations tested only coriander/cumin seed oil combination showed synergistic interactions both in antibacterial (FICI : 0.25-0.50 and antioxidant (CI : 0.79 activities. A high positive correlation between total phenolic content and antibacterial activity against most of the studied bacteria (R2 = 0.688 - 0.917 as well as antioxidant capacity (R2 = 0.828 was also observed. TLC-bioautography-guided screening and subsequent combination studies revealed that two compounds corresponding to Rf values 0.35 from coriander seed oil and 0.53 from cumin seed oil exhibited both synergistic antibacterial and antioxidant activities. The bioactive compound corresponding to Rf 0.35 from coriander seed oil was identified as linalool (68.69% and the bioactive compound corresponding to Rf 0.53 from cumin seed oil was

  12. Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Galani, Irene; Orlandou, Konstantina; Moraitou, Helen; Petrikkos, George; Souli, Maria

    2014-04-01

    The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller-Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time-kill methodology using tubes containing an inoculum of 5×10(5)CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24h for colony counting. Synergy was defined as ≥2log10CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate-concentration combinations in time-kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5h and 24h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time-kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii. Copyright © 2014. Published by Elsevier B.V.

  13. Multiple levels of synergistic collaboration in termite lignocellulose digestion.

    Directory of Open Access Journals (Sweden)

    Michael E Scharf

    Full Text Available In addition to evolving eusocial lifestyles, two equally fascinating aspects of termite biology are their mutualistic relationships with gut symbionts and their use of lignocellulose as a primary nutrition source. Termites are also considered excellent model systems for studying the production of bioethanol and renewable bioenergy from 2nd generation (non-food feedstocks. While the idea that gut symbionts are the sole contributors to termite lignocellulose digestion has remained popular and compelling, in recent years host contributions to the digestion process have become increasingly apparent. However, the degree to which host and symbiont, and host enzymes, collaborate in lignocellulose digestion remain poorly understood. Also, how digestive enzymes specifically collaborate (i.e., in additive or synergistic ways is largely unknown. In the present study we undertook translational-genomic studies to gain unprecedented insights into digestion by the lower termite Reticulitermes flavipes and its symbiotic gut flora. We used a combination of native gut tissue preparations and recombinant enzymes derived from the host gut transcriptome to identify synergistic collaborations between host and symbiont, and also among enzymes produced exclusively by the host termite. Our findings provide important new evidence of synergistic collaboration among enzymes in the release of fermentable monosaccharides from wood lignocellulose. These monosaccharides (glucose and pentoses are highly relevant to 2(nd-generation bioethanol production. We also show that, although significant digestion capabilities occur in host termite tissues, catalytic tradeoffs exist that apparently favor mutualism with symbiotic lignocellulose-digesting microbes. These findings contribute important new insights towards the development of termite-derived biofuel processing biotechnologies and shed new light on selective forces that likely favored symbiosis and, subsequently, group living in

  14. Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition.

    Science.gov (United States)

    Kosic, Milica; Arsikin-Csordas, Katarina; Paunovic, Verica; Firestone, Raymond A; Ristic, Biljana; Mircic, Aleksandar; Petricevic, Sasa; Bosnjak, Mihajlo; Zogovic, Nevena; Mandic, Milos; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2016-10-28

    We investigated the in vitro and in vivo anticancer effect of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-d-glucose (2DG). NDI-triggered LMP and 2DG-mediated glycolysis block synergized in inducing rapid ATP depletion, mitochondrial damage, and reactive oxygen species production, eventually leading to necrotic death of U251 glioma cells but not primary astrocytes. NDI/2DG-induced death of glioma cells was partly prevented by lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol, suggesting the involvement of LMP and oxidative stress in the observed cytotoxicity. LMP-inducing agent chloroquine also displayed a synergistic anticancer effect with 2DG, whereas glucose deprivation or glycolytic inhibitors iodoacetate and sodium fluoride synergistically cooperated with NDI, thus further indicating that the anticancer effect of NDI/2DG combination was indeed due to LMP and glycolysis block. The two agents synergistically induced ATP depletion, mitochondrial depolarization, oxidative stress, and necrotic death also in B16 mouse melanoma cells. Moreover, the combined oral administration of NDI and 2DG reduced in vivo melanoma growth in C57BL/6 mice by inducing necrotic death of tumor cells, without causing liver, spleen, or kidney toxicity. Based on these results, we propose that NDI-triggered LMP causes initial mitochondrial damage that is further increased by 2DG due to the lack of glycolytic ATP required to maintain mitochondrial health. This leads to a positive feedback cycle of mitochondrial dysfunction, ATP loss, and reactive oxygen species production, culminating in necrotic cell death. Therefore, the combination of LMP-inducing agents and glycolysis inhibitors seems worthy of further exploration as an anticancer strategy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. What is Life? Among Other Things, It's a Synergistic Effect!

    Directory of Open Access Journals (Sweden)

    Peter Corning

    2008-10-01

    Full Text Available There have been many different ways of characterizing and describing the phenomenon of life over the years. One aspect that has not often been stressed is lifersquo;s emergent propertiesmdash;the synergies that are produced when many elements or parts combine to produce distinctive new ldquo;wholesrdquo;. Indeed, complex living systems represent a multi-leveled, multi-faceted hierarchy of synergistic effects that has evolved over several billion years. Some of the many examples of synergy at various levels of life are briefly described, and it is emphasized that life is still creating itself and still exploring its potentialities.

  16. Synergistic Effect of Lupenone and Caryophyllene Oxide against Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Glendy Polanco-Hernández

    2013-01-01

    Full Text Available The in vitro trypanocidal activity of a 1 : 4 mixture of lupenone and caryophyllene oxide confirmed a synergistic effect of the terpenoids against epimastigotes forms of T. cruzi (IC50=10.4 μg/mL, FIC = 0.46. In addition, testing of the terpenoid mixture for its capacity to reduce the number of amastigote nests in cardiac tissue and skeletal muscle of infected mice showed a reduction of more than 80% at a dose level of 20.8 mg·kg−1·day−1.

  17. Synergistic effects of some essential oils against fungal spoilage on pear fruit.

    Science.gov (United States)

    Nikkhah, Mehdi; Hashemi, Maryam; Habibi Najafi, Mohammad B; Farhoosh, Reza

    2017-09-18

    The development of natural protective agents as alternatives to chemical fungicides is currently in the spotlight. In the present investigation, chemical composition and antifungal activities of thyme, cinnamon, rosemary and marjoram essential oils (EO), as well as synergism of their possible double and triple combinations were investigated. The compositions of the oils were determined by GC/MS. For determination of antifungal activity against Penicillium expansum and Botrytis cinerea, a broth microdilution method was used. The possible interactions of some essential oil combinations were performed by the two and three-dimensional checkerboard assay and isobologram construction. An in vivo antifungal assay was performed by artificial wounding of pear fruits. The maximum antifungal activity was demonstrated by thyme and cinnamon oils which displayed lower MIC values whereas rosemary and marjoram oils with MIC range between 2500 and 10,000μg/mL exhibited weak antifungal activities against tested fungi. In synergy testing, some double combinations (thyme/cinnamon, thyme/rosemary, cinnamon/rosemary) were found to be synergistic (FICi≤0.5). The triple combination of thyme, cinnamon and rosemary was synergistic for B. cinerea and P. expansum (FICi values of 0.5 and 0.375, respectively); while combination of cinnamon, marjoram and thyme exhibited additive and synergistic effect against P. expansum (FIC=0.625) and B. cinerea (FIC=0.375) respectively. The usage of a mathematical Gompertz model in relation to fungal kinetics, showed that the model could be used to predict growth curves (R 2 =0.993±0.05). For B. cinerea, Gompertz parameters for double and triple combination treatments showed significant increase in lag phase (1.92 and 2.92days, respectively) compared to single treatments. Increase lag time up to 2.82days (P<0.05) also observed in P. expansum treated by triple combination of EOs. Base on the results, the lowest maximum growth rate (0.37mm/day) was observed

  18. Herbicidal Activities of Some Allelochemicals and Their Synergistic Behaviors toward Amaranthus tricolor L.

    Directory of Open Access Journals (Sweden)

    Nawasit Chotsaeng

    2017-10-01

    Full Text Available Seven allelochemicals, namely R-(+-limonene (A, vanillin (B, xanthoxyline (C, vanillic acid (D, linoleic acid (E, methyl linoleate (F, and (±-odorine (G, were investigated for their herbicidal activities on Chinese amaranth (Amaranthus tricolor L.. At 400 μM, xanthoxyline (C showed the greatest inhibitory activity on seed germination and seedling growth of the tested plant. Both vanillic acid (D and (±-odorine (G inhibited shoot growth, however, apart from xanthoxyline (C, only vanillic acid (D could inhibit root growth. Interestingly, R-(+-limonene (A lightly promoted root length. Other substances had no allelopathic effect on seed germination and seedling growth of the tested plant. To better understand and optimize the inhibitory effects of these natural herbicides, 21 samples of binary mixtures of these seven compounds were tested at 400 μM using 0.25% (v/v Tween® 80 as a control treatment. The results showed that binary mixtures of R-(+-limonene:xanthoxyline (A:C, vanillin:xanthoxyline (B:C, and xanthoxyline:linoleic acid (C:E exhibited strong allelopathic activities on germination and seedling growth of the tested plant, and the level of inhibition was close to the effect of xanthoxyline (C at 400 µM and was better than the effect of xanthoxyline (C at 200 µM. The inhibition was hypothesized to be from a synergistic interaction of each pair of alleochemicals. Mole ratios of each pair of allelochemicals ((A:C, (B:C, and (C:E were then evaluated, and the best ratios of the binary mixtures A:C, B:C and C:E were found to be 2:8, 2:8, and 4:6 respectively. These binary mixtures significantly inhibited germination and shoot and root growth of Chinese amaranth at low concentrations. The results reported here highlight a synergistic behavior of some allelochemicals which could be applied in the development of potential herbicides.

  19. Nonlinear Synergistic Emergence and Predictability in Complex Systems: Theory and Hydro-Climatic Applications

    Science.gov (United States)

    Perdigão, Rui A. P.; Hall, Julia; Pires, Carlos A. L.; Blöschl, Günter

    2017-04-01

    Classical and stochastic dynamical system theories assume structural coherence and dynamic recurrence with invariants of motion that are not necessarily so. These are grounded on the unproven assumption of universality in the dynamic laws derived from statistical kinematic evaluation of non-representative empirical records. As a consequence, the associated formulations revolve around a restrictive set of configurations and intermittencies e.g. in an ergodic setting, beyond which any predictability is essentially elusive. Moreover, dynamical systems are fundamentally framed around dynamic codependence among intervening processes, i.e. entail essentially redundant interactions such as couplings and feedbacks. That precludes synergistic cooperation among processes that, whilst independent from each other, jointly produce emerging dynamic behaviour not present in any of the intervening parties. In order to overcome these fundamental limitations, we introduce a broad class of non-recursive dynamical systems that formulate dynamic emergence of unprecedented states in a fundamental synergistic manner, with fundamental principles in mind. The overall theory enables innovations to be predicted from the internal system dynamics before any a priori information is provided about the associated dynamical properties. The theory is then illustrated to anticipate, from non-emergent records, the spatiotemporal emergence of multiscale hyper chaotic regimes, critical transitions and structural coevolutionary changes in synthetic and real-world complex systems. Example applications are provided within the hydro-climatic context, formulating and dynamically forecasting evolving hydro-climatic distributions, including the emergence of extreme precipitation and flooding in a structurally changing hydro-climate system. Validation is then conducted with a posteriori verification of the simulated dynamics against observational records. Agreement between simulations and observations is

  20. Synergistic antibaterial activity of medicinal plants essential oils with biogenic silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Fatemeh Oroojalian

    2017-10-01

    Full Text Available Objective(s: Development of a nanobiosystem by using plant essential oils with green synthesized silver nanoparticles that present synergistic antibacterial activity for overcoming antibiotic resistance in pathogenic bacteria. Material and Methods: Essential oils (EOs of Kelussia odoratissima and Teucrium polium extracted by hydrodistillation were analyzed by gas chromatography-mass spectrometry (GC-MS. Then leaf aqueous extract of K. odoratissima prepared and used for green synthesise of silver nanoparticles (SNPs.  The oils, and the colloidal preparations of silver nanoparticles, were then subjected to microdilution technique using ELISA reader to determine their minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC on Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli O157: H7, Salmonella enterica and Pseudomonas aeruginosa. The type of interaction between EO and SNPs was also determined by calculating the fractional inhibitory concentration index and isibologram type. Results: GC-MS analysis of K. odoratissima EO showed (Z-ligustilide, (Z-3-butylidene-phthalide,  limonene and β-phellandren as main constiuents, while T. polium EO has β-caryophylene, germacrene D, γ-cadinene, (Z-nerolidol, camphor, β-pinene, α- camphene, linalool and α-humulene. T. polium EO has more potent antibacterial property at MIC of 0.16-1.25 mg/ml compared to K. odoratissima (MIC of 0.3-2.5 mg/ml. Silver nanoparticles showed a potent antibacterial property (MIC of 0.006-0.025 mg/ml, and its colloidal suspension with plant EOs revealed a pathogen-dependent synergistic and additive effect based on calculated fractional inhibitory concentration index (FICi.

  1. Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2005-02-01

    Full Text Available Abstract Background Recent studies have shown that gamma interferon (IFN-γ synergizes with the innate IFNs (IFN-α and IFN-β to inhibit herpes simplex virus type 1 (HSV-1 replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV replication. Results We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE genes (IE1 and IE2 revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. Conclusion These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.

  2. Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling.

    Science.gov (United States)

    Pansters, N A; Langen, R C; Wouters, E F; Schols, A M

    2013-05-01

    Muscle wasting is associated with poor prognosis in chronic obstructive pulmonary disease (COPD). Exercise stimulates muscle recovery, but its efficacy is variable, depending on the clinical condition and medical treatment. Systemic glucocorticoids, commonly administered in high doses during acute disease exacerbations or as maintenance treatment in end-stage disease, are known to contribute to muscle wasting. As muscle mass recovery involves insulin-like growth factor (IGF)-I signaling, which can be stimulated by anabolic steroids, the impact of glucocorticoids and the effect of simultaneous IGF-I stimulation by anabolic steroids on muscle recovery and growth were investigated. The effects of, and interactions between, glucocorticoid and IGF-I signaling on skeletal muscle growth were assessed in differentiating C2C12 myocytes. As proof of principle, we performed a post hoc analysis stratifying patients by glucocorticoid use of a clinical trial investigating the efficacy of anabolic steroid supplementation on muscle recovery in muscle-wasted patients with COPD. Glucocorticoids strongly impaired protein synthesis signaling, myotube formation, and muscle-specific protein expression. In contrast, in the presence of glucocorticoids, IGF-I synergistically stimulated myotube fusion and myofibrillar protein expression, which corresponded with restored protein synthesis signaling by IGF-I and increased transcriptional activation of muscle-specific genes by glucocorticoids. In COPD patients on maintenance glucocorticoid treatment, the clinical trial also revealed an enhanced effect of anabolic steroids on muscle mass and respiratory muscle strength. In conclusion, synergistic effects of anabolic steroids and glucocorticoids on muscle recovery may be caused by relief of the glucocorticoid-imposed blockade on protein synthesis signaling, allowing effective translation of glucocorticoid-induced accumulation of muscle-specific gene transcripts.

  3. OSU-2S/sorafenib synergistic antitumor combination against hepatocellular carcinoma: The role of PKCδ/p53

    Directory of Open Access Journals (Sweden)

    Hany A Omar

    2016-11-01

    Full Text Available Background: Sorafenib (Nexavar® is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC. However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices < 1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusions: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity towards both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol.

  4. Hazards and Benefits of Drug Interaction

    Science.gov (United States)

    Labianca, Dominick A.

    1978-01-01

    Most cases of drug toxicity are direct consequences of drug misuse--either intentional or inadvertent. Discusses two types of drug interaction--synergistic and antagonistic. The former produces a combined effect greater than the sum of the effects of the individual drugs concerned; the latter is produced when the desired action of one drug is…

  5. INSECT AND MYCOFLORA INTERACTIONS IN MAIZE FLOUR ...

    African Journals Online (AJOL)

    Ten species isolated from maize flour with T. castaneum were A. pullulans, Auxarthron spp., C. herbarum, Eurotium sp., Phoma glomerata, Neosauorya spp., Scopulariopsis brevicaulis, Rhizopus oryzae, R. stolonifer and Wallemia sebi. These results suggest an association and a synergistic interaction between important ...

  6. Synergistic antioxidant activity of green tea with some herbs

    Directory of Open Access Journals (Sweden)

    Dheeraj P Jain

    2011-01-01

    Full Text Available Cardiovascular diseases, cancer, arthritis, etc. are caused by free radicals that are byproducts of metabolic pathways. Selected plants namely Vitis vinifera, Phyllanthus emblica L., Punica granatum, Cinnamomum cassia, Ginkgo biloba L., and Camellia sinensis Linn. are reported to produce antioxidant property. This study is undertaken to support the hypothesis that formulation of a polyherbal combination of these plants shows a synergistic effect with green tea. The extracts of each drug were characterized by phytochemical studies and tests for phenolics and flavonoids. In vitro antioxidant activity for individual drug and its combination was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH, superoxide, and nitric oxide free radical scavenging methods. Our results suggest that a combination of all these herbs with green tea can synergistically enhance antioxidant activity and thus lower doses of each herb with green tea may be used. Antioxidant potential of polyherbal combination was also comparable to that of standard ascorbic acid. Studies showed that selected individual plants contained abundant quantity of phenolics and flavonoids and their polyherbal combination with green tea was found to produce best antioxidant activity among all individual extracts. This will help in avoiding undesirable side effects due to higher doses of single herb.

  7. Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics.

    Science.gov (United States)

    Li, Hongzhe; Steyger, Peter S

    2009-01-01

    Acoustic exposure to high intensity and/or prolonged noise causes temporary or permanent threshold shifts in auditory perception, reflected by reversible or irreversible damage in the cochlea. Aminoglycoside antibiotics, used for treating or preventing life-threatening bacterial infections, also induce cytotoxicity in the cochlea. Combined noise and aminoglycoside exposure, particularly in neonatal intensive care units, can lead to auditory threshold shifts greater than simple summation of the two insults. The synergistic toxicity of acoustic exposure and aminoglycoside antibiotics is not limited to simultaneous exposures. Prior acoustic insult which does not result in permanent threshold shifts potentiates aminoglycoside ototoxicity. In addition, exposure to subdamaging doses of aminoglycosides aggravates noise-induced cochlear damage. The mechanisms by which aminoglycosides cause auditory dysfunction are still being unraveled, but likely include the following: 1) penetration into the endolymphatic fluid of the scala media, 2) permeation of nonselective cation channels on the apical surface of hair cells, and 3) generation of toxic reactive oxygen species and interference with other cellular pathways. Here we discuss the effect of combined noise and aminoglycoside exposure to identify pivotal synergistic events that can potentiate ototoxicity, in addition to a current understanding of aminoglycoside trafficking within the cochlea. Preventing the ototoxic synergy of noise and aminoglycosides is best achieved by using non-ototoxic bactericidal drugs, and by attenuating perceived noise intensity when life-saving aminoglycoside therapy is required.

  8. Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

  9. 16.1% Efficient Hysteresis-Free Mesostructured Perovskite Solar Cells Based on Synergistically Improved ZnO Nanorod Arrays

    KAUST Repository

    Mahmood, Khalid

    2015-06-01

    Significant efficiency improvements are reported in mesoscopic perovskite solar cells based on the development of a low-temperature solution-processed ZnO nanorod (NR) array exhibiting higher NR aspect ratio, enhanced electron density, and substantially reduced work function than conventional ZnO NRs. These features synergistically result in hysteresis-free, scan-independent, and stabilized devices with an efficiency of 16.1%. Electron-rich, nitrogen-doped ZnO (N:ZnO) NR-based electron transporting materials (ETMs) with enhanced electron mobility produced using ammonium acetate show consistently higher efficiencies by one to three power points than undoped ZnO NRs. Additionally, the preferential electrostatic interaction between the -nonpolar facets of N:ZnO and the conjugated polyelectrolyte polyethylenimine (PEI) has been relied on to promote the hydrothermal growth of high aspect ratio NR arrays and substantially improve the infiltration of the perovskite light absorber into the ETM. Using the same interactions, a conformal PEI coating on the electron-rich high aspect ratio N:ZnO NR arrays is -successfully applied, resulting in a favorable work function shift and altogether leading to the significant boost in efficiency from <10% up to >16%. These results largely surpass the state-of-the-art PCE of ZnO-based perovskite solar cells and highlight the benefits of synergistically combining mesoscale control with doping and surface modification. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

    Science.gov (United States)

    Chen, Di; Li, Patrick Wai-Lun; Goldstein, Benjamin A; Cai, Waijiao; Thomas, Emma Lynn; Chen, Fen; Hubbard, Alan E; Melov, Simon; Kapahi, Pankaj

    2013-12-26

    Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Synergistic antimicrobial activity between pentacyclic triterpenoids and antibiotics against Staphylococcus aureus strains

    Directory of Open Access Journals (Sweden)

    Navaratnam Parasakthi

    2011-06-01

    Full Text Available Abstract Background There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin against reference strains of Staphylococcus aureus. Methods and Results The activity of the standard antibiotics and compounds on reference methicillin-sensitive and resistant strains of S. aureus were determined using the macrodilution broth method. The minimum inhibitory concentration (MIC of the compounds was compared with that of the standard antibiotics. The interaction between any two antimicrobial agents was estimated by calculating the fractional inhibitory concentration (FIC index of the combination. The various combinations of antibiotics and compounds reduced the MIC to a range of 0.05 to 50%. Conclusion Pentacyclic triterpenoids have shown anti-staphylococcal activities and although individually weaker than common antibiotics produced from bacteria and fungi, synergistically these compounds may use different mechanism of action or pathways to exert their antimicrobial effects, as implicated in the lowered MICs. Therefore, the use of current antibiotics could be maintained in their combination with plant-derived antibacterial agents as a therapeutic option in the treatment of S. aureus infections.

  12. Synergistic effects of non-Apis bees and honey bees for pollination services

    Science.gov (United States)

    Brittain, Claire; Williams, Neal; Kremen, Claire; Klein, Alexandra-Maria

    2013-01-01

    In diverse pollinator communities, interspecific interactions may modify the behaviour and increase the pollination effectiveness of individual species. Because agricultural production reliant on pollination is growing, improving pollination effectiveness could increase crop yield without any increase in agricultural intensity or area. In California almond, a crop highly dependent on honey bee pollination, we explored the foraging behaviour and pollination effectiveness of honey bees in orchards with simple (honey bee only) and diverse (non-Apis bees present) bee communities. In orchards with non-Apis bees, the foraging behaviour of honey bees changed and the pollination effectiveness of a single honey bee visit was greater than in orchards where non-Apis bees were absent. This change translated to a greater proportion of fruit set in these orchards. Our field experiments show that increased pollinator diversity can synergistically increase pollination service, through species interactions that alter the behaviour and resulting functional quality of a dominant pollinator species. These results of functional synergy between species were supported by an additional controlled cage experiment with Osmia lignaria and Apis mellifera. Our findings highlight a largely unexplored facilitative component of the benefit of biodiversity to ecosystem services, and represent a way to improve pollinator-dependent crop yields in a sustainable manner. PMID:23303545

  13. Synergistic effects of non-Apis bees and honey bees for pollination services.

    Science.gov (United States)

    Brittain, Claire; Williams, Neal; Kremen, Claire; Klein, Alexandra-Maria

    2013-03-07

    In diverse pollinator communities, interspecific interactions may modify the behaviour and increase the pollination effectiveness of individual species. Because agricultural production reliant on pollination is growing, improving pollination effectiveness could increase crop yield without any increase in agricultural intensity or area. In California almond, a crop highly dependent on honey bee pollination, we explored the foraging behaviour and pollination effectiveness of honey bees in orchards with simple (honey bee only) and diverse (non-Apis bees present) bee communities. In orchards with non-Apis bees, the foraging behaviour of honey bees changed and the pollination effectiveness of a single honey bee visit was greater than in orchards where non-Apis bees were absent. This change translated to a greater proportion of fruit set in these orchards. Our field experiments show that increased pollinator diversity can synergistically increase pollination service, through species interactions that alter the behaviour and resulting functional quality of a dominant pollinator species. These results of functional synergy between species were supported by an additional controlled cage experiment with Osmia lignaria and Apis mellifera. Our findings highlight a largely unexplored facilitative component of the benefit of biodiversity to ecosystem services, and represent a way to improve pollinator-dependent crop yields in a sustainable manner.

  14. Synergistic effects of parental and embryonic exposure to predation risk on prey offspring size at emergence.

    Science.gov (United States)

    Donelan, Sarah C; Trussell, Geoffrey C

    2018-01-01

    Cues signaling predation risk can strongly influence prey phenotypes both within and between generations. Parental and embryonic effects have been shown to operate independently in response to predation risk, but how they interact to shape offspring life history traits remains largely unknown. Here, we conducted experiments to examine the synergistic impacts of parental and embryonic experiences with predation risk on offspring size at emergence in the snail, Nucella lapillus, which is an ecologically important intermediate consumer on rocky intertidal shores. We found that when embryos were exposed to predation risk, the offspring of risk-experienced parents emerged larger than those of parents that had no risk experience. This response was not the result of increased development time, greater resource availability, or fewer emerging offspring, but may have occurred because both parental and embryonic experiences with risk increased growth efficiency, perhaps by reducing embryonic respiration rates under risk. Our results highlight the potential for organisms to be influenced by a complex history of environmental signals with important consequences for individual fitness and predator-prey interactions. © 2017 by the Ecological Society of America.

  15. Synergistic effect of fluoride and laser irradiation for the inhibition of the demineralization of dental enamel

    Science.gov (United States)

    Lee, Raymond; Chan, Kenneth H.; Jew, Jamison; Simon, Jacob C.; Fried, Daniel

    2017-02-01

    Both laser irradiation and fluoride treatment alone are known to provide increased resistance to acid dissolution. CO2 lasers tuned to a wavelength of 9.3 μm can be used to efficiently convert the carbonated hydroxyapatite of enamel to a much more acid resistant purer phase hydroxyapatite (HAP). Further studies have shown that fluoride application to HAP yields fluoroapatite (FAP) which is even more resistant against acid dissolution. Previous studies show that CO2 lasers and fluoride treatments interact synergistically to provide significantly higher protection than either method alone, but the mechanism of interaction has not been elucidated. We recently observed the formation of microcracks or a "crazed" zone in the irradiated region that is resistant to demineralization using high-resolution microscopy. The microcracks are formed due to the slight contraction of enamel due to transformation of carbonated hydroxyapatite to the more acid resistant pure phase hydroxyapatite (HAP) that has a smaller lattice. In this study, we test the hypothesis that these small cracks will provide greater adhesion for topical fluoride for greater protection against acid demineralization.

  16. 75 FR 60321 - Spinosad; Pesticide Tolerances

    Science.gov (United States)

    2010-09-30

    .... Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data..., Brassica leafy vegetables, citrus, fruiting vegetables, herbs, banana, grape, several cereal grains, and... consumption in a particular area, the exposure estimate [[Page 60324

  17. 21 CFR 520.2130 - Spinosad.

    Science.gov (United States)

    2010-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... in § 510.600 of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets once a... felis) on dogs for 1 month. (3) Limitations. Federal law restricts this drug to use by or on the order...

  18. Herd Clustering: A synergistic data clustering approach using collective intelligence

    KAUST Repository

    Wong, Kachun

    2014-10-01

    Traditional data mining methods emphasize on analytical abilities to decipher data, assuming that data are static during a mining process. We challenge this assumption, arguing that we can improve the analysis by vitalizing data. In this paper, this principle is used to develop a new clustering algorithm. Inspired by herd behavior, the clustering method is a synergistic approach using collective intelligence called Herd Clustering (HC). The novel part is laid in its first stage where data instances are represented by moving particles. Particles attract each other locally and form clusters by themselves as shown in the case studies reported. To demonstrate its effectiveness, the performance of HC is compared to other state-of-the art clustering methods on more than thirty datasets using four performance metrics. An application for DNA motif discovery is also conducted. The results support the effectiveness of HC and thus the underlying philosophy. © 2014 Elsevier B.V.

  19. Synergistic extraction behaviour of americium from simulated acidic waste solutions

    International Nuclear Information System (INIS)

    Pathak, P.N.; Veeraraghavan, R.; Mohapatra, P.K.; Manchanda, V.K.

    1998-01-01

    The extraction behaviour of americium has been investigated with mixtures of 3-phenyl-4-benzoyl-5-isoxazolone (PBI) and oxodonors viz. tri-n-butyl phosphate (TBP), tri-n-octyl phosphine oxide (TOPO) and di-n-butyl octanamide (DBOA) using dodecane as the diluent from 1-6 M HNO 3 media. It is observed that D Am remains unaltered with PBI concentration (in the range 0.06-0.1 M) at 1.47 M TBP in the entire range of HNO 3 concentration. PBI and TBP in combination appears more promising compared to other synergistic systems. The possibility of using this mixture for americium removal from high level liquid waste solution has been explored. Extraction studies indicated that prior removal of uranium by 20% TBP in dodecane is helpful in the quantitative recovery of americium in three contacts. Effect of lanthanides on D Am is found to be marginal. (orig.)

  20. Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems.

    Science.gov (United States)

    Rudilla, Héctor; Fusté, Ester; Cajal, Yolanda; Rabanal, Francesc; Vinuesa, Teresa; Viñas, Miguel

    2016-09-12

    The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 μg/mL, whereas the MBEC of each antimicrobial separately was 500 μg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.

  1. Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Jong, Edwin de; Langendijk, Johannes A.; Kampinga, Harm H.; Coppes, Robert P.

    2010-01-01

    Radiation-induced fibrosis is a severe side effect of radiotherapy. TGF-β and radiation synergistically induce expression of the profibrotic PAI-1 gene and this cooperation potentially involves p53. Here, we demonstrate that p53 is both indispensable and sufficient for the radiation effect inducing synergistic activation of PAI-1 by radiation and TGF-β.

  2. Synergistic extraction of actinides : Part I. Hexa-and pentavalent actinides

    International Nuclear Information System (INIS)

    Patil, S.K.; Ramakrishna, V.V.

    1980-01-01

    A detailed discussion on the reported literature on the synergistic extraction of hexa- and pentavalent actinide ions, by different combinations of extractants and from different aqueous media, is presented. Structural aspects of the various complexes involved in synergism also are reviewed. A short account of the applications based on synergistic extraction is also given. (author)

  3. Injectable, NIR/pH-Responsive Nanocomposite Hydrogel as Long-Acting Implant for Chemophotothermal Synergistic Cancer Therapy.

    Science.gov (United States)

    Xu, Xiaoyu; Huang, Ziyuan; Huang, Zeqian; Zhang, Xuefei; He, Siyu; Sun, Xiaoqi; Shen, Yifeng; Yan, Mina; Zhao, Chunshun

    2017-06-21

    In this study, gold nanorods (GNRs) were incorporated into the hydrogel networks formed by the copolymerization of N-isopropylacrylamide (NIPAm) and methacrylated poly-β-cyclodextrin (MPCD)-based macromer to fabricate an injectable and near-infrared (NIR)/pH-responsive poly(NIPAm-co-MPCD)/GNRs nanocomposite hydrogel, which could serve as a long-acting implant for chemophotothermal synergistic cancer therapy. The nanocomposite hydrogel showed superior mechanical and swelling properties, gelation characteristics, and excellent NIR-responsive property. A hydrophobic acid-labile adamantane-modified doxorubicin (AD-DOX) prodrug was loaded into the hydrogel efficiently by host-guest interaction. The nanocomposite hydrogel exhibited a manner of sustained drug release and could sustain the slow and steady release of DOX for more than 1 month. The pH-responsive release of DOX from the nanocomposite hydrogel was observed owing to the cleavage of acid-labile hydrazone bond between DOX and the adamantyl group in acidic environment. NIR irradiation could accelerate the release of DOX from the networks, which was controlled by the collapse of the hydrogel networks induced by photothermal effect of GNRs. The in vitro cytotoxicity test demonstrated the excellent biocompatibility and photothermal effect of the nanocomposite hydrogel. Moreover, the in situ-forming hydrogel showed promising tissue biocompatibility in the mouse model study. The in vivo antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemophotothermal synergistic therapy with reduced adverse effects owing to the prolonged drug retention in the tumor region and efficient photothermal effect. Therefore, this injectable and NIR/pH-responsive nanocomposite hydrogel exhibited great potential as a long term drug delivery platform for chemophotothermal synergistic cancer therapy.

  4. DOCA stimulates salt appetite in Zucker rats: effect of dose, synergistic action with central angiotensin II, and obesity.

    Science.gov (United States)

    Omouessi, S T; Falconetti, C; Fernette, B; Thornton, S N

    2007-09-14

    An enhanced sodium appetite is found in rats by the synergist interaction of peripheral mineralocorticoids, deoxycorticosterone acetate (DOCA), and central angiotensin II (AngII), the synergy theory. We used obese Zucker rats which have a predisposition to develop hypertension under appropriate salt conditions to examine this synergy response between AngII and different low doses of DOCA on 2% NaCl intake. Obese and lean Zucker rats on low sodium food were treated systemically with 0.5, 1 and 2 mg/kg/day of DOCA for 3 days, before receiving i.c.v. AngII (10 pmol) on the fourth day. Food, fluid intakes and urine outputs were measured daily throughout. Plasma aldosterone levels were also analysed. Results showed that AngII alone increased water but not salt intake, whereas all three doses of DOCA by themselves enhanced daily salt intake during the treatment period. The lowest dose of DOCA plus AngII did not stimulate an enhanced sodium consumption. The 1 mg/kg was the threshold dose of DOCA for a synergistic response, and with 2 mg/kg DOCA the obese rats consumed nearly 2-fold more hypertonic NaCl solution than the leans. Moreover, obese baseline plasma levels of aldosterone were more elevated than the lean rats. In conclusion, in adult Zucker rats a threshold level of mineralocorticoid is required for the salt stimulating action of central AngII. In the obese rat the synergistic effect is enhanced with higher doses of mineralocorticoid, suggesting that the plasma level of aldosterone could be a prominent factor, which may predispose the obese to salt-sensitivity and, possibly, subsequently to hypertension under appropriate conditions.

  5. Classification of suppressor additives based on synergistic and antagonistic ensemble effects

    International Nuclear Information System (INIS)

    Broekmann, P.; Fluegel, A.; Emnet, C.; Arnold, M.; Roeger-Goepfert, C.; Wagner, A.; Hai, N.T.M.; Mayer, D.

    2011-01-01

    Highlights: → Three fundamental types of suppressor additives for copper electroplating could be identified by means of potential transient measurements. → These suppressor additives differ in their synergistic and antagonistic interplay with anions that are chemisorbed on the metallic copper surface during electrodeposition. → In addition these suppressor chemistries reveal different barrier properties with respect to cupric ions and plating additives (Cl, SPS). - Abstract: Three fundamental types of suppressor additives for copper electroplating could be identified by means of potential transient measurements. These suppressor additives differ in their synergistic and antagonistic interplay with anions that are chemisorbed on the metallic copper surface during electrodeposition. In addition these suppressor chemistries reveal different barrier properties with respect to cupric ions and plating additives (Cl, SPS). While the type-I suppressor selectively forms efficient barriers for copper inter-diffusion on chloride-terminated electrode surfaces we identified a type-II suppressor that interacts non-selectively with any kind of anions chemisorbed on copper (chloride, sulfate, sulfonate). Type-I suppressors are vital for the superconformal copper growth mode in Damascene processing and show an antagonistic interaction with SPS (Bis-Sodium-Sulfopropyl-Disulfide) which involves the deactivation of this suppressor chemistry. This suppressor deactivation is rationalized in terms of compositional changes in the layer of the chemisorbed anions due to the competition of chloride and MPS (Mercaptopropane Sulfonic Acid) for adsorption sites on the metallic copper surface. MPS is the product of the dissociative SPS adsorption within the preexisting chloride matrix on the copper surface. The non-selectivity in the adsorption behavior of the type-II suppressor is rationalized in terms of anion/cation pairing effects of the poly-cationic suppressor and the anion

  6. Synergistic infection of two viruses MCMV and SCMV increases the accumulations of both MCMV and MCMV-derived siRNAs in maize.

    Science.gov (United States)

    Xia, Zihao; Zhao, Zhenxing; Chen, Ling; Li, Mingjun; Zhou, Tao; Deng, Congliang; Zhou, Qi; Fan, Zaifeng

    2016-02-11

    The co-infection of Maize chlorotic mottle virus (MCMV) and Sugarcane mosaic virus (SCMV) can cause maize lethal necrosis. However, the mechanism underlying the synergistic interaction between these two viruses remains elusive. In this study, we found that the co-infection of MCMV and SCMV increased the accumulation of MCMV. Moreover, the profiles of virus-derived siRNAs (vsiRNAs) from MCMV and SCMV in single- and co-infected maize plants were obtained by high-throughput sequencing. Our data showed that synergistic infection of MCMV and SCMV increased remarkably the accumulation of vsiRNAs from MCMV, which were mainly 22 and 21 nucleotides in length. The single-nucleotide resolution maps of vsiRNAs revealed that vsiRNAs were almost continuously but heterogeneously distributed throughout MCMV and SCMV genomic RNAs, respectively. Moreover, we predicted and annotated dozens of host transcript genes targeted by vsiRNAs. Our results also showed that maize DCLs and several AGOs RNAs were differentially accumulated in maize plants with different treatments (mock, single or double inoculations), which were associated with the accumulation of vsiRNAs. Our findings suggested possible roles of vsiRNAs in the synergistic interaction of MCMV and SCMV in maize plants.

  7. Identifying Natural syNergist from Pongamia pinnata Using High-Speed Counter-Current Chromatography Combined with Isobolographic Analysis

    Directory of Open Access Journals (Sweden)

    Hao Yin

    2017-03-01

    Full Text Available For identifying the synergistic compounds from Pongamia pinnata, an approach based on high-speed counter-current chromatography (HSCCC combined with isobolographic analysis was designed to detect the synergistic effects in the complex mixture [...

  8. Synergistic interaction of ten essential oils against Haemonchus contortus in vitro

    Science.gov (United States)

    Anthelmintic resistance in sheep gastrointestinal nematodes is a worldwide problem. Multi-drug resistant haemonchosis is the most serious impediment for small ruminant systems, and there are no new drug candidates currently under development. Molecules from natural sources have demonstrated anthelmi...

  9. Synergistic interactions between corrosion and wear at titanium-based dental implant connections: A scoping review.

    Science.gov (United States)

    Apaza-Bedoya, K; Tarce, M; Benfatti, C A M; Henriques, B; Mathew, M T; Teughels, W; Souza, J C M

    2017-12-01

    Two-piece implant systems are mainly used in oral implantology involving an osseointegrated implant connected to an abutment, which supports prosthetic structures. It is well documented that the presence of microgaps, biofilms and oral fluids at the implant-abutment connection can cause mechanical and biological complications. The aim of this review paper was to report the degradation at the implant-abutment connection by wear and corrosion processes taking place in the oral cavity. Most of the retrieved studies evaluated the wear and corrosion (tribocorrosion) of titanium-based materials used for implants and abutments in artificial saliva. Electrochemical and wear tests together with microscopic techniques were applied to validate the tribocorrosion behavior of the surfaces. A few studies inspected the wear on the inner surfaces of the implant connection as a result of fatigue or removal of abutments. The studies reported increased microgaps after fatigue tests. In addition, data suggest that micromovements occurring at the contacting surfaces can increase the wear of the inner surfaces of the connection. Biofilms and/or glycoproteins act as lubricants, although they can also amplify the corrosion of the surfaces. Consequently, loosening of the implant-abutment connection can take place during mastication. In addition, wear and corrosion debris such as ions and micro- and nanoparticles released into the surrounding tissues can stimulate peri-implant inflammation that can lead to pathologic bone resorption. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Synergistic interaction of radiation and octylphenol evaluated by tradescantia-micronucleus assay

    Energy Technology Data Exchange (ETDEWEB)

    Shin, H. S.; Lee, J. H. [Chungnam National University, Taejon (Korea, Republic of); Lee, B. H.; Kim, J. K. [KAERI, Taejon (Korea, Republic of)

    2003-07-01

    Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'endocrine disruptors' because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end- point for assessing their effects. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation and bisphenol A. The MCN frequencies in the pollen mother cells treated with octylphenol were 4.20, 7.27, 4.93 MCN/100 tetrads for 1, 5 and 10 {mu}M, respectively. On the other hand, the frequencies were 10.13, 19.27, 24.47 MCN/100 tetrads for the octylphenol treatments (1, 5, and 10 {mu}M) combined with 30 cGy irradiation. The MCN frequency of 30 cGy control was 8.00 MCN/100 tetrads for the octylphenol treatments (1, 5, and 10{mu}M) combined with 30 cGy irradiation. The MCN frequency of 30 cGy control was 8.00 MCN/100 tetrads. It is known from the result that the Trad-MCN assay can be an excellent tool for the detection of biologically harmful effects of environmental toxicants or synthetic chemicals.

  11. Synergistic interactions of dynamic ridesharing and battery electric vehicles land use, transit, and auto pricing policies.

    Science.gov (United States)

    2015-10-01

    It is widely recognized that new vehicle and fuel technology is necessary, but not sufficient, to meet deep greenhouse gas (GHG) : reductions goals for both the U.S. and the state of California. Demand management strategies (such as land use, transit...

  12. Further investigations on the synergistic interaction of hyperthermia with sparsely ionizing radiations

    International Nuclear Information System (INIS)

    Schrader-Reichhardt, U.; Markus, B.

    1978-01-01

    Experiments were performed with tetraploid asynchronous and synchronous Chinese hamster ovary fibroblasts. Irradiations were done with 15 MeV electrons at two different irradiation depths and with X-rays of 200 and 29 kV. For several diploid Chinese hamster cell lines it has been shown in literature that S-cells are much more sensitive to combined treatment of hyperthermia and radiation than G1-cells. With our tetraploid CHO fibroblasts we could find no additional enhancement of S-phase killing, converting radioresistant S-cells to the most radiation sensitive phase. (orig./AJ) [de

  13. Synergistic Interactions with PI3K Inhibition that Induce Apoptosis. | Office of Cancer Genomics

    Science.gov (United States)

    Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition.

  14. Synergistic interaction in simultaneous exposure to Streptomyces californicus and Stachybotrys chartarum

    DEFF Research Database (Denmark)

    Huttunen, K.; Pelkonen, J.; Nielsen, Kristian Fog

    2004-01-01

    and their metabolites, although the cytotoxicity and inflammatory potential of certain individual microbes have been reported. In this study, we investigated the inflammatory responses of mouse RAW264.7 macrophages after exposure to six indoor air microbes (Aspergillus versicolor, Penicillium spinulosum, Stachybotrys...

  15. Synergistic effects of seasonal rainfall, parasites and demography on fluctuations in springbok body condition

    Science.gov (United States)

    Turner, Wendy C.; Versfeld, Wilferd D.; Kilian, J. Werner; Getz, Wayne M.

    2011-01-01

    Summary 1. Seasonality of rainfall can exert a strong influence on animal condition and on host-parasite interactions. The body condition of ruminants fluctuates seasonally in response to changes in energy requirements, foraging patterns and resource availability, and seasonal variation in parasite infections may further alter ruminant body condition. 2. This study disentangles effects of rainfall and gastrointestinal parasite infections on springbok (Antidorcas marsupialis) body condition and determines how these factors vary among demographic groups. 3. Using data from four years and three study areas, we investigated i) the influence of rainfall variation, demographic factors and parasite interactions on parasite prevalence or infection intensity, ii) whether parasitism or rainfall is a more important predictor of springbok body condition and iii) how parasitism and condition vary among study areas along a rainfall gradient. 4. We found that increased parasite intensity is associated with reduced body condition only for adult females. For all other demographic groups, body condition was significantly related to prior rainfall and not to parasitism. Rainfall lagged by two months had a positive effect on body condition. 5. Adult females showed evidence of a “periparturient rise” in parasite intensity, and had higher parasite intensity and lower body condition than adult males after parturition and during early lactation. After juveniles were weaned, adult females had lower parasite intensity than adult males. Sex differences in parasitism and condition may be due to differences between adult females and males in the seasonal timing of reproductive effort and its effects on host immunity, as well as documented sex differences in vulnerability to predation. 6. Our results highlight that parasites and the environment can synergistically affect host populations, but that these interactions might be masked by their interwoven relationships, their differential

  16. Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

    Science.gov (United States)

    Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

    2016-01-01

    Antibacterial resistance has dramatically increased and resulted in serious health problems worldwide. One appealing strategy to overcome this resistance problem is the use of combinations of antibacterial compounds to increase their potency. The objective of this study is to determine the synergistic effects of artocarpin for ampicillin, norfloxacin, and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA) as well as the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli. A broth microdilution method (1.95-250 µg/mL) was used to determine the minimum inhibitory concentration (MIC) of artocarpin and the antibiotics. Any synergistic effects were evaluated at their own MIC using the checkerboard method and a time-kill assay at 37 °C for 24 h. Artocarpin showed antibacterial activity against MRSA and E. coli with an MIC value of 62.5 µg/mL, and against P. aeruginosa with an MIC value of 250 µg/mL. The interaction of artocarpin with all tested antibiotics produced synergistic effects against MRSA with a fractional inhibitory concentration index (FICI) of 0.15-0.37. In addition, a combination of artocarpin and norfloxacin showed a synergistic effect against E. coli with an FICI value of 0.37, while the combinations of artocarpin and tetracycline as well as artocarpin and norfloxacin exhibited synergy interactions against P. aeruginosa with FICI values of 0.24 and 0.37, respectively. Time-kill assays indicated that artocarpin enhanced the antimicrobial activities of tetracycline, ampicillin, and norfloxacin against MRSA as well as Gram-negative bacteria.

  17. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Saleha B Vuyyuri

    Full Text Available Ascorbic acid (AA exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3-PO on the viability of three non-small cell lung cancer (NSCLC cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with

  18. Beneficial synergistic effect on bio-oil production from co-liquefaction of sewage sludge and lignocellulosic biomass.

    Science.gov (United States)

    Leng, Lijian; Li, Jun; Yuan, Xingzhong; Li, Jingjing; Han, Pei; Hong, Yuchun; Wei, Feng; Zhou, Wenguang

    2018-03-01

    Co-liquefaction of municipal sewage sludge (MSS) and lignocellulosic biomass such as rice straw or wood sawdust at different mixing ratios and the characterization of the obtained bio-oil and bio-char were investigated. Synergistic effects were found during co-processing of MSS with biomass for production of bio-oil with higher yield and better fuel properties than those from individual feedstock. The co-liquefaction of MSS/rice straw (4/4, wt) increased the bio-oil yield from 22.74% (bio-oil yield from liquefaction of MSS individually) or 23.67% (rice straw) to 32.45%. Comparable increase on bio-oil yield was also observed for MSS/wood sawdust mixtures (2/6, wt). The bio-oils produced from MSS/biomass mixtures were mainly composed of esters and phenols with lower boiling points (degradation temperatures) than those from individual feedstock (identified with higher heavy bio-oil fractions). These synergistic effects were probably resulted from the interactions between the intermittent products of MSS and those of biomass during processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Is There a Positive Synergistic Effect of Biochar and Compost Soil Amendments on Plant Growth and Physiological Performance?

    Directory of Open Access Journals (Sweden)

    M. Lukas Seehausen

    2017-02-01

    Full Text Available The combination of biochar (BC with compost has been suggested to be a promising strategy to promote plant growth and performance, but although “synergistic” effects have been stated to occur, full-factorial experiments are few, and explicit tests for synergism are lacking. We tested the hypothesis that a combination of BC and spent mushroom substrate (SMS has a positive synergistic effect on plant growth and physiological performance in a nutrient-limited growing media. A greenhouse experiment with a full factorial design was conducted using mixed-wood BC (3.0 kg·m−2 and SMS (1.5 kg·m−2 (the combination was not co-composted as organic soil amendments for the annual Abutilon theophrasti and the perennial Salix purpurea. Several measurements related to plant growth and physiological performance were taken throughout the experiment. Contrary to the hypothesis, we found that the combination of BC + SMS had neutral or antagonistic interactive effects on many plant growth traits. Antagonistic effects were found on maximum leaf area, above- and belowground biomass, reproductive allocation, maximum plant height, chlorophyll fluorescence, and stomatal conductance of A. theophrasti. The effect on S. purpurea was mostly neutral. We conclude that the generalization that BC and compost have synergistic effects on plant performance is not supported.

  20. Synergistic Effects of Expectancy and Value on Homework Engagement: The Case for a Within-Person Perspective.

    Science.gov (United States)

    Nagengast, Benjamin; Trautwein, Ulrich; Kelava, Augustin; Lüdtke, Oliver

    2013-05-01

    Historically, expectancy-value models of motivation assumed a synergistic relation between expectancy and value: motivation is high only when both expectancy and value are high. Motivational processes were studied from a within-person perspective, with expectancies and values being assessed or experimentally manipulated across multiple domains and the focus being placed on intraindividual differences. In contrast, contemporary expectancy-value models in educational psychology concentrate almost exclusively on linear effects of expectancy and value on motivational outcomes, with a focus on between-person differences. Recent advances in latent variable methodology allow both issues to be addressed in observational studies. Using the expectancy-value model of homework motivation as a theoretical framework, this study estimated multilevel structural equation models with latent interactions in a sample of 511 secondary school students and found synergistic effects between domain-specific homework expectancy and homework value in predicting homework engagement in 6 subjects. This approach not only brings the "×" back into expectancy-value theory but also reestablishes the within-person perspective as the appropriate level of analysis for latent expectancy-value models.

  1. Highly transparent and rollable PVA-co-PE nanofibers synergistically reinforced with epoxy film for flexible electronic devices.

    Science.gov (United States)

    Xiong, Bing; Zhong, Weibing; Zhu, Qing; Liu, Ke; Li, Mufang; Sun, Gang; Wang, Dong

    2017-12-14

    The development of electronics towards a more functions-integrated, flexible and stretchable direction requires mechanically flexible substrates with high thermal and dimensional stability and optical transparency. Herein, rolls of an optically transparent PVA-co-PE nanofibrous membrane/epoxy composite with synergistically enhanced thermal stability, very low CTE, and outstanding mechanical properties are reported. The nanoscale size, the unique inter-stack structure, and the strong interfacial interactions between the PVA-co-PE nanofibers and the epoxy contribute to the synergistic effects. Because of the match between the refractive index (RI) of the PVA-co-PE nanofibers and the epoxy matrix, the visible light transmittance of nanocomposite film could be as high as 85% and the composite film was still optically transparent with a nanofiber loading content of up to 61.7 wt%. The break strength and compliance matrix of the composite film with a high fiber loading of 61.7 wt% increased by 2.3 times of that of the neat epoxy film and exceeded 3000 m 2 N -1 , respectively. PVA-co-PE nanofibers have a very low CTE value (3.634 × 10 -6 K -1 ) and could be applicable as a reinforcement to reduce the thermal expansion of epoxy. Furthermore, we developed a flexible alternating current electroluminescent (ACEL) device based on the transparent composite film and the experimental results showed that the transparent composite film could serve as substrate for flexible electronic devices. In addition, their electrical and optical properties were evaluated.

  2. Systematic chemical analysis approach reveals superior antioxidant capacity via the synergistic effect of flavonoid compounds in red vegetative tissues

    Science.gov (United States)

    Qin, Xiaoxiao; Lu, Yanfen; Peng, Zhen; Fan, Shuangxi; Yao, Yuncong

    2018-02-01

    The flavonoid system comprises an abundance of compounds with multiple functions; however, their potential synergism in antioxidant function remains unclear. We established an approach using ever-red (RL) and ever-green leaves (GL) of crabapple cultivars during their development to determine interrelationships among flavonoid compounds. RL scored significantly better than GL in terms of the type, composition, and diversity of flavonoids than GL. Principal component analysis predicted flavonoids in RL to have positive interaction effects, and the total antioxidant capacity was significantly higher than the sum of antioxidant capacities of the individual compounds. This synergy was verified by the high antioxidant capacity in rat serum after feeding on red leaves. Our findings suggest that the synergistic effect is a result of the high transcription levels regulated by McMYBs in RL. In summary, individual flavonoids cooperate in a flavonoid system, thus producing a synergistic antioxidant effect, and the approach used herein can provide insights into the roles of flavonoids and other compounds in future studies.

  3. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  4. Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval)).

    Science.gov (United States)

    Wu, Lipeng; Huo, Xin; Zhou, Xiaolong; Zhao, Duoyong; He, Weizhong; Liu, Shenghong; Liu, Hejiang; Feng, Ting; Wang, Cheng

    2017-11-01

    Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites ( Tetranychus cinnabarinus (Boisduval) ) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p -cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides.

  5. Synergistic action of radiation and chemical carcinogen in induction of leukemia in mice, 3

    International Nuclear Information System (INIS)

    Kajitani, Takashi

    1982-01-01

    1. There was no synergistic interaction of radiation and N-nitrosoethylurea (NEU) in induction of leukemia if irradiation was confined to the thymic region. 2. Cell kinetics in the thymus and bone marrow of young-adult mice were studied following whole-body X-irradiation or local X-irradiation over the thymus. It was found that whole-body X-irradiation caused drastic injuries, followed by a vigorous regeneration in both thymus and bone marrow, whereas local X-irradiation caused much milder changes in the thymus than whole-body X-irradiation, and caused no apparent changes in the bone marrow. 3. A single dose of 5 mg of NEU force administered by gastric intubation was found to be moderately leukemogenic, inducing thymic lymphomas in 37% of young adult female C57BL/6N mice. 4. Whole-body X-irradiation with 400R enhanced the incidence of thymic lymphoma when mice were irradiated 5 days prior to a single dose of NEU force administered by gastric intubation. In contrast, no enhancing effect was observed when the mice were irradiated 30 days prior to a single dose of NEU. 5. The results indicate that whole-body X-irradiation right before NEU administration plays a role in providing a cell population either in the thymus or bone marrow susceptible to NEU during postirradiation repair-period. (author)

  6. Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity

    Science.gov (United States)

    Ford, Rebecca J.; Fullerton, Morgan D.; Pinkosky, Stephen L.; Day, Emily A.; Scott, John W.; Oakhill, Jonathan S.; Bujak, Adam L.; Smith, Brennan K.; Crane, Justin D.; Blumer, Regje M.; Marcinko, Katarina; Kemp, Bruce E.; Gerstein, Hertzel C.; Steinberg, Gregory R.

    2017-01-01

    Metformin is the mainstay therapy for type 2 diabetes (T2D) and many patients also take salicylate-based drugs [i.e., aspirin (ASA)] for cardioprotection. Metformin and salicylate both increase AMP-activated protein kinase (AMPK) activity but by distinct mechanisms, with metformin altering cellular adenylate charge (increasing AMP) and salicylate interacting directly at the AMPK β1 drug-binding site. AMPK activation by both drugs results in phosphorylation of ACC (acetyl-CoA carboxylase; P-ACC) and inhibition of acetyl-CoA carboxylase (ACC), the rate limiting enzyme controlling fatty acid synthesis (lipogenesis). We find doses of metformin and salicylate used clinically synergistically activate AMPK in vitro and in vivo, resulting in reduced liver lipogenesis, lower liver lipid levels and improved insulin sensitivity in mice. Synergism occurs in cell-free assays and is specific for the AMPK β1 subunit. These effects are also observed in primary human hepatocytes and patients with dysglycaemia exhibit additional improvements in a marker of insulin resistance (proinsulin) when treated with ASA and metformin compared with either drug alone. These data indicate that metformin–salicylate combination therapy may be efficacious for the treatment of non-alcoholic fatty liver disease (NAFLD) and T2D. PMID:25742316

  7. Vibrio cholerae use pili and flagella synergistically to effect motility switching and conditional surface attachment

    Science.gov (United States)

    Utada, Andrew S.; Bennett, Rachel R.; Fong, Jiunn C. N.; Gibiansky, Maxsim L.; Yildiz, Fitnat H.; Golestanian, Ramin; Wong, Gerard C. L.

    2014-09-01

    We show that Vibrio cholerae, the causative agent of cholera, use their flagella and mannose-sensitive hemagglutinin (MSHA) type IV pili synergistically to switch between two complementary motility states that together facilitate surface selection and attachment. Flagellar rotation counter-rotates the cell body, causing MSHA pili to have periodic mechanical contact with the surface for surface-skimming cells. Using tracking algorithms at 5 ms resolution we observe two motility behaviours: ‘roaming', characterized by meandering trajectories, and ‘orbiting’, characterized by repetitive high-curvature orbits. We develop a hydrodynamic model showing that these phenotypes result from a nonlinear relationship between trajectory shape and frictional forces between pili and the surface: strong pili-surface interactions generate orbiting motion, increasing the local bacterial loiter time. Time-lapse imaging reveals how only orbiting mode cells can attach irreversibly and form microcolonies. These observations suggest that MSHA pili are crucial for surface selection, irreversible attachment, and ultimately microcolony formation.

  8. Synergistic effect of carbon nanotube and clay for improving the flame retardancy of ABS resin

    Energy Technology Data Exchange (ETDEWEB)

    Ma Haiyun [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Tong Lifang [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Xu Zhongbin [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Fang Zhengping [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China)

    2007-09-19

    Synergistic effect between multi-walled carbon nanotubes (MWNTs) and clay on improving the flame retardancy of acrylonitrile-butadiene-styrene (ABS) resin was studied. Flammability properties measured by a cone calorimeter revealed that incorporation of clay and MWNTs into ABS resin significantly reduced the peak heat release rate (PHRR) and slowed down the whole combustion process compared to the individually filled system based on clay or MWNTs. The flame retardancy of the ABS/clay/MWNTs nanocomposites was strongly affected by the formation of a network structure. Linear viscoelastic properties of the ABS nanocomposites showed that the coexistence of clay and MWNTs can enhance the network structure which can hinder the movement of polymer chains and improve flame retardancy. From transmission electron microscope analysis, MWNTs were shortened after combustion and there was no significant change in their diameters. For chars of ABS/clay/MWNTs nanocomposites, some MWNTs ran across between clay layers, indicating a strong interaction existed between clay and MWNTs. The existence of clay enhanced the graphitization degree of MWNTs during combustion. Clay can assist the elimination of dislocations and defects and the rearrangement of crystallites. Al{sub 2}O{sub 3}, one of the components of clay, acts as the catalyst of graphitization.

  9. Acid-base synergistic flame retardant wood pulp paper with high thermal stability.

    Science.gov (United States)

    Wang, Ning; Liu, Yuansen; Xu, Changan; Liu, Yuan; Wang, Qi

    2017-12-15

    Acid-catalytic degradation caused by acid source flame retardants is the main reason for a decline in thermal stability of flame-retarded lignocellulosic materials. In the present research, a guanidine phosphate (GP)/borax (BX) flame retardant system based on acid-base synergistic interaction was designed and used in wood pulp paper (WPP) to solve this problem. Results showed that the treated WPP obtained good flame retardancy with a limiting oxygen index (LOI) value of 35.7%. As a basic flame retardant, borax could chemically combine with the acids released by guanidine phosphate, thus decreasing the acidity of the system in the initial heating stage. In this way, acid-catalytic degradation is greatly retarded on the lignocelluloses to improve thermal stability (the temperature of maximum degradation peak from 286°C to 314°C). Meanwhile, borax was also advantageous to form a denser and firmer condensed phase through reinforcement of the acid-base reaction product, borophosphates, allowing it to provide a protective barrier with higher quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Protein-mediated efficient synergistic "antenna effect" in a ternary system in D₂O medium.

    Science.gov (United States)

    Ghorai, Shyamal Kr; Samanta, Swarna Kamal; Mukherjee, Manini; Ghosh, Sanjib

    2012-08-16

    A ternary system consisting of a protein, catechin (either + or - epimer), and Tb(III) in suitable aqueous buffer medium at physiological pH (= 6.8) has been shown to exhibit highly efficient "antenna effect". Steady state and time-resolved emission studies of each component in the binary complexes (protein with Tb(III) and (+)- or (-)-catechin with Tb(III)) and the ternary systems along with the molecular docking studies reveal that the efficient sensitization could be ascribed to the effective shielding of microenvironment of Tb(III) from O-H oscillator and increased Tb-C (+/-) interaction in the ternary systems in aqueous medium. The ternary system exhibits protein-mediated efficient antenna effect in D(2)O medium due to synergistic ET from both the lowest ππ* triplet state of Trp residue in protein and that of catechin apart from protection of the Tb(III) environment from matrix vibration. The simple system consisting of (+)- or (-)-catechin and Tb(III) in D(2)O buffer at pH 6.8 has been prescribed to be a useful biosensor.

  11. Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles.

    Science.gov (United States)

    Kim, Myung Goo; Jo, Sung Duk; Yhee, Ji Young; Lee, Beom Suk; Lee, So Jin; Park, Sung Gurl; Kang, Sun-Woong; Kim, Sun Hwa; Jeong, Ji Hoon

    2017-07-15

    A variety of VEGF inhibitors have been reported to treat cancers by suppressing tumor angiogenesis. Bevacizumab, a monoclonal VEGF antibody, was the first FDA approved anti-angiogenic agent for cancer treatments. However, bevacizumab shows modest therapeutic efficiency and often cause resistant problem in significant populations of cancer patients. To solve these problem, we investigated the therapeutic efficacy of siRNA drugs targeting VEGF and combination of the RNAi drug with bevacizumab for cancer treatments. For efficient VEGF siRNA delivery, chemically polymerized siRNAs were complexed with thiolated-glycol chitosan (psi(VEGF)/tGC). The poly-VEGF siRNA and thiolated-glycol chitosan formed stable nanoparticles via electrostatic interaction and chemical crosslinking, and showed high accumulation in tumor tissues resulting in efficient gene silencing. Both VEGF siRNA nanoparticles and bevacizumab had efficient therapeutic effects in tumor xenograft mouse models. Interestingly, most pronounced therapeutic efficacy was observed when the two distinct VEGF inhibitors were treated in combination revealing synergistic effects. The results showed that the psi(VEGF)/tGC nanoparticle mediated knockdown of VEGF exerts anti-tumor effects and the combination treatments with bevacizumab can extend the treatments options to conventional bevacizumab treatments for cancer therapy. Copyright © 2017. Published by Elsevier Inc.

  12. Origin of synergistic effect over Ni-based bimetallic surfaces: A density functional theory study

    Science.gov (United States)

    Fan, Chen; Zhu, Yi-An; Xu, Yue; Zhou, Yan; Zhou, Xing-Gui; Chen, De

    2012-07-01

    Density functional theory calculations have been conducted to explore the physical origin of the synergistic effect over Ni-based surface alloys using methane dissociation as a probe reaction. Some late transition metal atoms (M = Cu, Ru, Rh, Pd, Ag, Pt, and Au) are substituted for surface Ni atoms to examine the variation in electronic structure and adsorption property of Ni(111). Two types of threefold hollow sites, namely, the Ni2M and Ni3 sites, are taken into account. The calculated results indicate that the variation in the CHx adsorption energy at the Ni2M and Ni3 sites is dominated by the ensemble and ligand effect, respectively, and the other factors such as surface and adsorbate distortion and electrostatic interaction affect the catalytic properties of the bimetallic surfaces to a smaller extent. Both the Brønsted-Evans-Polanyi relationship and the scaling correlation hold true on the Ni-based bimetallic surfaces. With the combination of these two linear energy relations, the corrected binding energy of atomic C is found to be a good descriptor for representing the catalytic activity of the alloyed surfaces. Considering the compromise between the catalytic activity and catalyst stability, we suggest that the Rh/Ni catalyst is a good candidate for methane dissociation.

  13. Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis.

    Directory of Open Access Journals (Sweden)

    Jon F Wilkins

    2016-04-01

    Full Text Available A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.e. unfit phenotypes with frequencies on the order of 1% can, under the right circumstances, be expected to be driven primarily by synergistic epistatic interactions. Conditions that are necessary, collectively, for this outcome include a strongly non-linear phenotypic landscape, strong (but not too strong selection against the disease phenotype, and "noise" in the genotype-phenotype map that is both environmental (extrinsic, time-correlated and developmental (intrinsic, uncorrelated and, in both cases, neither too little nor too great. These results suggest ways in which geneticists might identify, a priori, those disease traits for which an "epistatic explanation" should be sought, and in the process better focus ongoing searches for risk alleles.

  14. Synergistic effect of divalent cations in improving technological properties of cross-linked alginate beads.

    Science.gov (United States)

    Cerciello, Andrea; Del Gaudio, Pasquale; Granata, Veronica; Sala, Marina; Aquino, Rita P; Russo, Paola

    2017-08-01

    Gelling solution parameters are some of the most important variables in ionotropic gelation and consequently influence the technological characteristics of the product. To date, only a few studies have focused on the simultaneous use of multiple cations as gelling agents. With the aim to deeply explore this possibility, in this research we investigated the effect of two divalent cations (Ca 2+ and Zn 2+ ) on alginate beads formation and properties. Alginate beads containing prednisolone (P) as model drug were prepared by prilling technique. The main critical variables of the ionotropic gelation process i.e. composition of the aqueous feed solutions (sodium alginate and prednisolone concentration) and cross-linking conditions (Ca 2+ , Zn 2+ or Ca 2+ +Zn 2+ ), were studied. The obtained beads were characterized and their in vitro release performances were assessed in conditions simulating the gastrointestinal environment. Results evidenced a synergistic effect of the two cations, affecting positively both the encapsulation efficiency and the ability of the alginate polymeric matrix to control the drug release. A Ca 2+ /Zn 2+ ratio of 4:1, in fact, exploited the Ca 2+ ability of establish quicker electrostatic interactions with guluronic groups of alginate and the Zn 2+ ability to establish covalent-like bonds with carboxylate groups of both guluronic and mannuronic moieties of alginate. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Aluminium tolerance in rice is antagonistic with nitrate preference and synergistic with ammonium preference.

    Science.gov (United States)

    Zhao, Xue Qiang; Guo, Shi Wei; Shinmachi, Fumie; Sunairi, Michio; Noguchi, Akira; Hasegawa, Isao; Shen, Ren Fang

    2013-01-01

    Acidic soils are dominated chemically by more ammonium and more available, so more potentially toxic, aluminium compared with neutral to calcareous soils, which are characterized by more nitrate and less available, so less toxic, aluminium. However, it is not known whether aluminium tolerance and nitrogen source preference are linked in plants. This question was investigated by comparing the responses of 30 rice (Oryza sativa) varieties (15 subsp. japonica cultivars and 15 subsp. indica cultivars) to aluminium, various ammonium/nitrate ratios and their combinations under acidic solution conditions. indica rice plants were generally found to be aluminium-sensitive and nitrate-preferring, while japonica cultivars were aluminium-tolerant and relatively ammonium-preferring. Aluminium tolerance of different rice varieties was significantly negatively correlated with their nitrate preference. Furthermore, aluminium enhanced ammonium-fed rice growth but inhibited nitrate-fed rice growth. The results suggest that aluminium tolerance in rice is antagonistic with nitrate preference and synergistic with ammonium preference under acidic solution conditions. A schematic diagram summarizing the interactions of aluminium and nitrogen in soil-plant ecosystems is presented and provides a new basis for the integrated management of acidic soils.

  16. Aqueous solutions of didecyldimethylammonium chloride and octaethylene glycol monododecyl ether: Toward synergistic formulations against enveloped viruses.

    Science.gov (United States)

    Nardello-Rataj, Véronique; Leclercq, Loïc

    2016-09-10

    Micellization of di-n-decyldimethylammonium chloride, [DiC10][Cl], and octaethylene glycol monododecyl ether, C12E8, mixtures have been investigated by surface tension and conductivity measurements. From these results, various physicochemical and thermodynamic key parameters (e.g. micellar mole fraction of [DiC10][Cl], interaction parameter, free energy of micellization, etc.) have been evaluated and discussed in detail. The results prove high synergistic effect between the two surfactants. Based on these results, the virucidal activity of an equimolar mixture of [DiC10][Cl] and C12E8 has been investigated. A marked synergism was observed on lipid-containing deoxyribonucleic and ribonucleic acid viruses, such as herpes virus, respiratory syncytial virus, and vaccinia viruses. In contrast, Coxsackievirus (non-enveloped virus) was not inactivated. These results support that the mechanism is based on the extraction of lipids and/or proteins from the envelope inside the mixed micelles. This extraction creates "holes" the size of which increases with concentration up to a specific value which triggers the virus inactivation. Such a mixture could be used to extend the spectrum of virucidal activity of the amphiphiles virucides commonly employed in numerous disinfectant solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval

    Directory of Open Access Journals (Sweden)

    Lipeng Wu

    2017-11-01

    Full Text Available Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%, and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides.

  18. Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Guan Wang

    Full Text Available High-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate of less than 40%. Therefore, new agents are urgently needed to overcome chemotherapy resistance so as to improve the treatment outcome of this deadly disease. Histone deacetylase (HDAC inhibitors (HDACIs represent a novel class of anticancer drugs. Recent studies demonstrated that HDACIs can down-regulate the CHK1 pathway by which cancer cells can develop resistance to conventional chemotherapy drugs. This prompted our hypothesis that combining HDACIs with DNA damaging chemotherapeutic drugs for treating neuroblastoma would result in enhanced anti-tumor activities of these drugs. Treatment of high-risk neuroblastoma cell lines with a novel pan-HDACI, panobinostat (LBH589, resulted in dose-dependent growth arrest and apoptosis in 4 high-risk neuroblastoma cell lines. Further, the combination of panobinostat with cisplatin, doxorubicin, or etoposide resulted in highly synergistic antitumor interactions in the high-risk neuroblastoma cell lines, independent of the sequence of drug administration. This was accompanied by cooperative induction of apoptosis. Furthermore, panobinostat treatment resulted in substantial down-regulation of CHK1 and its downstream pathway and abrogation of the G2 cell cycle checkpoint. Synergistic antitumor interactions were also observed when the DNA damaging agents were combined with a CHK1-specific inhibitor, LY2603618. Contrary to panobinostat treatment, LY2603618 treatments neither resulted in abrogation of the G2 cell cycle checkpoint nor enhanced cisplatin, doxorubicin, or etoposide-induced apoptosis in the high-risk neuroblastoma cells. Surprisingly, LY2603618 treatments caused substantial down-regulation of total CDK1. Despite this discrepancy between panobinostat and LY2603618, our results indicate that suppression of the CHK1 pathway by panobinostat is at least partially responsible for the synergistic antitumor interactions

  19. Nonlinear optical enhancement induced by synergistic effect of graphene nanosheets and CdS nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Baohua, E-mail: bhzhu@henu.edu.cn, E-mail: yzgu@henu.edu.cn; Cao, Yawan; Wang, Chong; Wang, Ji; Gu, Yuzong, E-mail: bhzhu@henu.edu.cn, E-mail: yzgu@henu.edu.cn [Institute of Microsystem, School of Physics and Electronics, Henan University, Kaifeng 475004 (China); Wang, Fangfang [Key Laboratory of Infrared Imaging Materials and Detectors, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083 (China)

    2016-06-20

    CdS nanocrystals are attached on graphene nanosheets and their nonlinear optical properties are investigated by picosecond Z-scan technique at 532 nm. We found that synergistic effect between the graphene and CdS makes a major enhancement on the nonlinear optical absorption of graphene/CdS nanohybrid in comparison with cooperative effect, and the synergistic improvement is restricted by nonradiative defects in hybrid. The synergistic mechanism involving the local field theory and charge transfer evolution is proposed.

  20. A multi-functional nanoplatform for tumor synergistic phototherapy

    Science.gov (United States)

    Zhang, Huijuan; Jiao, Xiaojing; Chen, Qianqian; Ji, Yandan; Zhang, Xiaoge; Zhu, Xing; Zhang, Zhenzhong

    2016-02-01

    Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform.

  1. A multi-functional nanoplatform for tumor synergistic phototherapy

    International Nuclear Information System (INIS)

    Zhang, Huijuan; Jiao, Xiaojing; Chen, Qianqian; Ji, Yandan; Zhang, Xiaoge; Zhu, Xing; Zhang, Zhenzhong

    2016-01-01

    Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO 2 @MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO 2 @MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO 2 @MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform. (paper)

  2. Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation.

    Science.gov (United States)

    Stehling, Michael K; Guenther, Enric; Mikus, Paul; Klein, Nina; Rubinsky, Liel; Rubinsky, Boris

    2016-01-01

    Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation.

  3. Synergistic effect of fragrant herbs in Japanese scent sachets.

    Science.gov (United States)

    Fujiwara, Yumi; Ito, Michiho

    2015-02-01

    The sedative activity of eight aromatic natural medicines that are traditionally used in Japanese scent sachets was examined using an open field test with mice. Galangal (Kaempferia galanga), patchouli (Pogostemon cablin), sandalwood (Santalum album), spikenard (Nardostachys chinensis), cinnamon (Cinnamomum cassia), clove (Syzygium aromaticum), star anise (Illicium verum), and borneol (Dryobalanops aromatica) distilled oils were used. These natural medicines have various pharmacological effects. For example, galangal has insecticidal activity and clove extracts possess strong total antioxidant activity. Aromatherapy, a well-known complementary medicine system that uses inhalation, has recently attracted much attention. The sedative activity of inhaled aromatic compounds or essential oils has been examined by measuring the spontaneous motor activity of mice in an open field test. The galangal, patchouli, sandalwood, spikenard, and borneol oils showed significant sedative effects. The effect was stronger for a mixture of the five oils than for any of the single oils. This suggests that the oil mixture may have synergistic activity. Sedative activity was not observed when inactive oils (cinnamon, clove, and star anise) were added to the mixture of the five active oils. Georg Thieme Verlag KG Stuttgart · New York.

  4. MODELLING SYNERGISTIC EYE MOVEMENTS IN THE VISUAL FIELD

    Directory of Open Access Journals (Sweden)

    BARITZ Mihaela

    2015-06-01

    Full Text Available Some theoretical and practical considerations about eye movements in visual field are presented in the first part of this paper. These movements are developed into human body to be synergistic and are allowed to obtain the visual perception in 3D space. The theoretical background of the eye movements’ analysis is founded on the establishment of movement equations of the eyeball, as they consider it a solid body with a fixed point. The exterior actions, the order and execution of the movements are ensured by the neural and muscular external system and thus the position, stability and movements of the eye can be quantified through the method of reverse kinematic. The purpose of these researches is the development of a simulation model of human binocular visual system, an acquisition methodology and an experimental setup for data processing and recording regarding the eye movements, presented in the second part of the paper. The modeling system of ocular movements aims to establish the binocular synergy and limits of visual field changes in condition of ocular motor dysfunctions. By biomechanical movements of eyeball is established a modeling strategy for different sort of processes parameters like convergence, fixation and eye lens accommodation to obtain responses from binocular balance. The results of modelling processes and the positions of eye ball and axis in visual field are presented in the final part of the paper.

  5. Synergistic effects of resistance training and protein intake: practical aspects.

    Science.gov (United States)

    Guimarães-Ferreira, Lucas; Cholewa, Jason Michael; Naimo, Marshall Alan; Zhi, X I A; Magagnin, Daiane; de Sá, Rafaele Bis Dal Ponte; Streck, Emilio Luiz; Teixeira, Tamiris da Silva; Zanchi, Nelo Eidy

    2014-10-01

    Resistance training is a potent stimulus to increase skeletal muscle mass. The muscle protein accretion process depends on a robust synergistic action between protein intake and overload. The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy. Although both essential and non-essential amino acids are necessary for hypertrophy, the intake of free L-leucine or high-leucine whole proteins has been specifically shown to increase the initiation of translation that is essential for elevated MPS. The literature supports the use of protein intake following resistance-training sessions to enhance MPS; however, less understood are the effects of different protein sources and timing protocols on MPS. The sum of the adaptions from each individual training session is essential to muscle hypertrophy, and thus highlights the importance of an optimal supplementation protocol. The aim of this review is to present recent findings reported in the literature and to discuss the practical application of these results. In that light, new speculations and questions will arise that may direct future investigations. The information and recommendations generated in this review should be of benefit to clinical dietitians as well as those engaged in sports. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Synergistic degradation of konjac glucomannan by alkaline and thermal method.

    Science.gov (United States)

    Jin, Weiping; Mei, Ting; Wang, Yuntao; Xu, Wei; Li, Jing; Zhou, Bin; Li, Bin

    2014-01-01

    The application of konjac glucomannan (KGM) in the food industry is always limited by its high viscosity. Hereby, low-viscosity KGM was prepared by alkaline-thermal degradation method. This process was demonstrated by the changes of average molecular weight and a kinetic model was developed. The results revealed that high alkalinity and high temperature had a synergetic effect on degradation. The structure of hydrolysates was evaluated by periodate oxidation and their fluidly properties were researched by rheology measurements. The degradation was divided into two regimes. The rate of the first regime (within 1h) is higher than that of the second one (last 1h). It is found that alkaline hydrolysis and deacetylation have a synergistic effect on the degradation under high alkalinity (pH 9.2) and low temperature condition (25 °C). Finally, rheology parameters showed alkaline-thermal degradation is a promising way that can be applied in practice to degrade KGM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Synergistic Smart Fuel For In-pile Nuclear Reactor Measurements

    Energy Technology Data Exchange (ETDEWEB)

    James A. Smith; Dale K. Kotter; Randall A. Ali; Steven L . Garrett

    2013-10-01

    In March 2011, an earthquake of magnitude 9.0 on the Richter scale struck Japan with its epicenter on the northeast coast, near the Tohoku region. In addition to the immense physical destruction and casualties across the country, several nuclear power plants (NPP) were affected. It was the Fukushima Daiichi NPP that experienced the most severe and irreversible damage. The earthquake brought the reactors at Fukushima to an automatic shutdown and because the power transmission lines were damaged, emergency diesel generators (EDGs) were activated to ensure that there was continued cooling of the reactors and spent fuel pools. The situation was being successfully managed until the tsunami hit about forty-five minutes later with a maximum wave height of approximately 15 m. The influx of water submerged the EDGs, the electrical switchgear, and dc batteries, resulting in the total loss of power to the reactors.2 At this point, the situation became critical. There was a loss of the sensors and instrumentation within the reactor that could have provided valuable information to guide the operators to make informed decisions and avoid the unfortunate events that followed. In the light of these events, we have developed and tested a potential self-powered thermoacoustic system, which will have the ability to serve as a temperature sensor and can transmit data independently of electronic networks. Such a device is synergistic with the harsh environment of the nuclear reactor as it utilizes the heat from the nuclear fuel to provide the input power.

  8. Synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses.

    Science.gov (United States)

    Kang, Hyunju; Kim, Chonsaeng; Kim, Dong-eun; Song, Jae-Hyoung; Choi, Miri; Choi, Kwangman; Kang, Mingu; Lee, Kyungjin; Kim, Hae Soo; Shin, Jin Soo; Kim, Janghwan; Han, Sang-Bae; Lee, Mi-Young; Lee, Su Ui; Lee, Chong-Kyo; Kim, Meehyein; Ko, Hyun-Jeong; van Kuppeveld, Frank J M; Cho, Sungchan

    2015-12-01

    Enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. However, no effective therapy is currently available for the treatment of these infections. We identified gemcitabine, a nucleoside-analog drug used for cancer treatment, from a screen of bioactive chemicals as a novel inhibitor of coxsackievirus B3 (CVB3) and enterovirus 71 (EV71). Gemcitabine potently inhibited the proliferation of CVB3 and EV71, as well as the replication of CVB3 and EV71 replicons, in cells with a low micromolar IC50 (1-5 μM). Its strong inhibitory effect was also observed in cells infected with human rhinoviruses, demonstrating broad-spectrum antiviral effects on enteroviruses. Mechanistically, an extensive analysis excluded the involvement of 2C, 3A, IRES-dependent translation, and also that of polyprotein processing in the antiviral effects of gemcitabine. Importantly, gemcitabine in combination with ribavirin, an antiviral drug currently being used against a few RNA viruses, exhibited a synergistic antiviral effect on the replication of CVB3 and EV71 replicons. Consequently, our results clearly demonstrate a new indication for gemcitabine as an effective broad-spectrum inhibitor of enteroviruses and strongly suggest a new therapeutic strategy using gemcitabine alone or in combination with ribavirin for the treatment of various diseases associated with enterovirus infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Enhanced Antimicrobial Activity Based on a Synergistic Combination of Sublethal Levels of Stresses Induced by UV-A Light and Organic Acids.

    Science.gov (United States)

    de Oliveira, Erick F; Cossu, Andrea; Tikekar, Rohan V; Nitin, Nitin

    2017-06-01

    used for inactivating microbes in food products, but these processes often significantly reduce the sensory and nutritional properties of food and are highly energy intensive. This study demonstrates that the combination of two natural food-grade antimicrobial agents with a sublethal level of physical stress in the form of UV-A light can greatly increase microbial load inactivation. In addition, this report elucidates the potential mechanisms for this synergistic interaction among physical and chemical stresses. Overall, these results provide a novel approach to develop antimicrobial solutions for food and water systems. Copyright © 2017 American Society for Microbiology.

  10. A Synergistic effect of artocarpanone from Artocarpus heterophyllus Lam. (Moraceae on the antibacterial activity of some antibiotics and their effect on membrane permeability

    Directory of Open Access Journals (Sweden)

    Abdi Wira Septama

    2017-06-01

    Full Text Available Aim/backgrounds: Artocarpanone isolated from Artocarpus heterophyllus Lam. (Moraceae possesses antibacterial activity. The present study investigated any interaction between artocarpanone and some antibiotics including tetracycline, ampicillin and norfloxacin against Methicillin-resistant Staphylococcus aureus (MRSA, Pseudomonas aeruginosa and Escherichia coli, as well as determining any disruptive effect on bacterial membranes. Materials and methods: A broth microdilution method was used for the susceptibility assay. Any synergistic effect was determined using a checerboard method, and any membrane disruption effect was investigated using a bacteriolysis assay and a measurement of the released 260 nm absorbing materials. Results and discussion: Artocarpanone exhibited weak antibacterial activities against MRSA and P. aeruginosa with MIC values of 125 and 500 µg/mL, respectively. However, it showed the strong antibacterial activity against E. coli (7.8 µg/mL. The interaction between artcarpanone with all tested antibiotics against P. aeruginosa and E. coli only revealed indifference and additive effects (FICI values of 0.75-1.25. The interaction between artocarpanone (31.2 µg/mL and norfloxacin (3.9 µg/mL exhibited a synergistic antibacterial activity against MRSA, with a fractional inhibitory concentration index (FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, a combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. Conclusion: These findings suggested that artocarpanone may be considered as an adjuvant to enhance the antibacterial activity of norfloxacin against MRSA. [J Complement Med Res 2017; 6(2.000: 186-191

  11. Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines.

    Science.gov (United States)

    Cekay, Michael John; Roesler, Stefanie; Frank, Tanja; Knuth, Anne-Kathrin; Eckhardt, Ines; Fulda, Simone

    2017-12-01

    Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. This synergism is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i.e. BV6, Birinapant), pointing to a broader relevance. Importantly, individual genetic knockdown of key components of necroptosis signaling, i.e. receptor-interacting protein (RIP) 1, RIP3 or mixed lineage kinase domain-like pseudokinase (MLKL), significantly protects from BV6/IFNγ-induced cell death. Similarly, pharmacological inhibitors of RIP1 (necrostatin-1(Nec-1)), RIP3 (GSK'872) or MLKL (necrosulfonamide (NSA)) significantly reduce BV6/IFNγ-stimulated cell death. Of note, IFN-regulatory factor (IRF)1 is required for BV6/IFNγ-mediated necroptosis, as IRF1 silencing provides protection from cell death. By comparison, antibodies blocking tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand (TRAIL) or CD95 ligand fail to inhibit BV6/IFNγ-induced cell death, pointing to a mechanism independently of death receptor ligands. This is the first report showing that Smac mimetics synergize with IFNγ to trigger necroptosis in apoptosis-resistant cancer cells with important implications for Smac mimetic-based strategies for the treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Theoretical studies on the synergistic extraction of Am3+and Eu3+with CMPO-HDEHP and CMPO-HEH[EHP] systems.

    Science.gov (United States)

    Huang, Pin-Wen; Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Song, Gang; Chai, Zhi-Fang; Shi, Wei-Qun

    2018-04-03

    In recent years, there has been a trend to use synergistic systems of neutral and acidic extractants into a single-solvent formulation to achieve Ln3+/An3+ extraction and separation via simplified processing schemes. In this study, geometrical structures, bonding nature, and thermodynamic stabilities of a series of possible extraction complexes of Am3+ and Eu3+ with two neutral-acid synergistic systems (CMPO-HDEHP and CMPO-HEH[EHP]) were theoretically studied using scalar-relativistic density functional theory (DFT). It is found that hydrogen bonds between neutral and acid ligands may greatly influence the Eu3+/Am3+ extraction and separation performance of the two synergistic systems. According to natural bond orbital (NBO) and energy decomposition analyses (EDA), the phosphoryl oxygen atoms of HDEHP or HEH[EHP] have higher affinity for Eu3+ and Am3+ than those of the CMPO ligand. Since weak but different extents of covalency exist in Eu- and Am-complexes, Eu3+/Am3+ separation via these two systems may be attributed to the different compositions of interactions between the metal ions and ligands. Thermodynamic analysis shows that the neutral complexes ML(NO3)2 (M = Eu and Am; L = [CMPO-DEHP]- and [CMPO-EH[EHP

  13. Synergistic activity and mode of action of flavonoids isolated from smaller galangal and amoxicillin combinations against amoxicillin-resistant Escherichia coli.

    Science.gov (United States)

    Eumkeb, G; Siriwong, S; Phitaktim, S; Rojtinnakorn, N; Sakdarat, S

    2012-01-01

    The smaller galangal is extracted, purified and identified the bioactive compounds. The purpose of this research was to investigate whether these isolated compounds have antibacterial and synergistic activity against amoxicillin-resistant Escherichia coli (AREC) when used singly and in combination with amoxicillin. The primarily mode of action is also studied. The galangin, kaempferide and kaempferide-3-O-β-d-glucoside were isolated. The minimum inhibitory concentrations(MIC) of amoxicillin and these flavonoids against AREC were between 500 and >1000 μg ml(-1). Synergistic activity was observed on combining amoxicillin with these flavonoids. The combinations of amoxicillin and these flavonoids exhibited a synergistic effect, reducing AREC cell numbers. Electron microscopy showed that these combinations damaged the ultrastructure of AREC cells. The results indicated that these combinations altered outer membrane permeability but not affecting cytoplasmic membrane. Enzyme assays showed that these flavonoids had an inhibitory activity against penicillinase. These results indicated that these flavonoids have the potential to reverse bacterial resistance to amoxicillin in AREC and may operate via three mechanisms: inhibition of peptidoglycan and ribosome synthesis, alteration of outer membrane permeability, and interaction with β-lactamases. These findings offer the potential to develop a new generation of phytopharmaceuticals to treat AREC. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  14. USING A DOE AND EIS TO EVALUATE THE SYNERGISTIC EFFECTS OF LOW TOXICITY INHIBITORS FOR MILD STEEL

    Directory of Open Access Journals (Sweden)

    G. V. Bueno

    2015-03-01

    Full Text Available Abstract Inhibitors are widely used to prevent corrosion in cooling-water systems, and their protective performance can be enhanced by combination. The aim of this paper is to identify possible synergistic effects between four low toxicity substances used as corrosion inhibitors for mild steel in industrial cooling-water systems. Electrochemical measurements were obtained following a design of experiments (DOE where the independent variables were the inhibitors concentrations and the response variable the charge transfer resistance estimated from impedance diagrams. Potentiodynamic polarization curves show that all of them act as anodic corrosion inhibitors. Among the tested formulations, only the interaction between sodium molybdate and sodium tungstate showed statistically significant effects, indicating that they can perform better when used together. The results of this work show the importance of using a statistical tool when designing inhibitor mixtures.

  15. Synergistic toxicity and physiological impact of imidacloprid alone and binary mixtures with seven representative pesticides on honey bee (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Yu Cheng Zhu

    Full Text Available Imidacloprid is the most widely used insecticide in the world. In this study, we used spraying methods to simulate field exposures of bees to formulated imidacloprid (Advise® 2FL alone and binary mixtures with seven pesticides from different classes. Synergistic toxicity was detected from mixtures of Advise (58.6 mg a.i./L imidacloprid+Domark (512.5 mg a.i. /L tetraconazole, Advise+Transform (58.5 mg a.i./L sulfoxaflor, and Advise+Vydate (68 mg a.i./L oxamyl, and mortality was significantly increased by 20%, 15%, and 26% respectively. The mixtures of Advise+Bracket (88.3 mg a.i./L acephate and Advise+Karate (62.2 mg a.i./L L-cyhalothrin showed additive interaction, while Advise+Belay (9.4 mg a.i./L clothianidin and Advise+Roundup (1217.5 mg a.i./L glyphosate had no additive/synergistic interaction. Spraying bees with the mixture of all eight pesticides increased mortality to 100%, significantly higher than all other treatments. Except Bracket which significantly suppressed esterase and acetylcholinesterase (AChE activities, other treatments of Advise-only and mixtures with other pesticides did not suppress enzyme activities significantly, including invertase, glutathione S-transferase (GST, and esterase and AChE. Immunity-related phenoloxidase (PO activities in survivors tended to be more variable among treatments, but mostly still statistically similar to the control. By using specific enzyme inhibitors, we demonstrated that honey bees mainly rely on cytochrome P450 monooxygenases (P450s for detoxifying Advise, while esterases and GSTs play substantially less roles in the detoxification. This study provided valuable information for guiding pesticide selection in premixing and tank mixing in order to alleviate toxicity risk to honey bees. Our findings indicated mixtures of Advise with detoxification-enzyme-inducing pesticides may help bees to detoxify Advise, while toxicity synergists may pose further risk to bees, such as the Bracket which not

  16. Synergistic toxicity and physiological impact of imidacloprid alone and binary mixtures with seven representative pesticides on honey bee (Apis mellifera).

    Science.gov (United States)

    Zhu, Yu Cheng; Yao, Jianxiu; Adamczyk, John; Luttrell, Randall

    2017-01-01

    Imidacloprid is the most widely used insecticide in the world. In this study, we used spraying methods to simulate field exposures of bees to formulated imidacloprid (Advise® 2FL) alone and binary mixtures with seven pesticides from different classes. Synergistic toxicity was detected from mixtures of Advise (58.6 mg a.i./L imidacloprid)+Domark (512.5 mg a.i. /L tetraconazole), Advise+Transform (58.5 mg a.i./L sulfoxaflor), and Advise+Vydate (68 mg a.i./L oxamyl), and mortality was significantly increased by 20%, 15%, and 26% respectively. The mixtures of Advise+Bracket (88.3 mg a.i./L acephate) and Advise+Karate (62.2 mg a.i./L L-cyhalothrin) showed additive interaction, while Advise+Belay (9.4 mg a.i./L clothianidin) and Advise+Roundup (1217.5 mg a.i./L glyphosate) had no additive/synergistic interaction. Spraying bees with the mixture of all eight pesticides increased mortality to 100%, significantly higher than all other treatments. Except Bracket which significantly suppressed esterase and acetylcholinesterase (AChE) activities, other treatments of Advise-only and mixtures with other pesticides did not suppress enzyme activities significantly, including invertase, glutathione S-transferase (GST), and esterase and AChE. Immunity-related phenoloxidase (PO) activities in survivors tended to be more variable among treatments, but mostly still statistically similar to the control. By using specific enzyme inhibitors, we demonstrated that honey bees mainly rely on cytochrome P450 monooxygenases (P450s) for detoxifying Advise, while esterases and GSTs play substantially less roles in the detoxification. This study provided valuable information for guiding pesticide selection in premixing and tank mixing in order to alleviate toxicity risk to honey bees. Our findings indicated mixtures of Advise with detoxification-enzyme-inducing pesticides may help bees to detoxify Advise, while toxicity synergists may pose further risk to bees, such as the Bracket which not only

  17. Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes.

    Science.gov (United States)

    Sun, Shutao; Mao, Ying; Lou, Hongxiang; Liu, Lei

    2015-07-07

    The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals.

  18. Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria.

    Science.gov (United States)

    Wu, Xiaozhe; Li, Zhan; Li, Xiaolu; Tian, Yaomei; Fan, Yingzi; Yu, Chaoheng; Zhou, Bailing; Liu, Yi; Xiang, Rong; Yang, Li

    2017-01-01

    Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs) and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT)-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001) and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin) on clinical bacterial strains ( Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii , and Escherichia coli ). The AZT-resistance genes ( ermA, ermB, ermC, mefA , and msrA ) were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L). When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7-AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus strain synergistically affected by DP7-AZT showed no noteworthy morphological changes, suggesting that a molecular-level mechanism plays an important role in the synergistic action of DP7-AZT. AMP DP7 plus the antibiotic AZT or VAN is more effective, especially against highly antibiotic-resistant strains.

  19. Synergistic Effects of Cellulosomal Xylanase and Cellulases from Clostridium cellulovorans on Plant Cell Wall Degradation

    OpenAIRE

    Murashima, Koichiro; Kosugi, Akihiko; Doi, Roy H.

    2003-01-01

    Plant cell walls are comprised of cellulose and hemicellulose and other polymers that are intertwined, and this complex structure presents a barrier to degradation by pure cellulases or hemicellulases. In this study, we determined the synergistic effects on corn cell wall degradation by the action of cellulosomal xylanase XynA and cellulosomal cellulases from Clostridium cellulovorans. XynA minicellulosomes and cellulase minicellulosomes were found to degrade corn cell walls synergistically b...

  20. Synergistic combinations of antifungals and antivirulence agents to fight against Candida albicans

    DEFF Research Database (Denmark)

    Cui, Jinhui; Ren, Biao; Tong, Yaojun

    2015-01-01

    -drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time......-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections....

  1. Development of a Synergistic Case-Based Micro anatomy Curriculum

    Science.gov (United States)

    McBride, Jennifer M.; Prayson, Richard A.

    2008-01-01

    This paper discusses the development of an interactive approach to teaching and assessing a micro anatomy curriculum in an innovative medical school program. As an alternative to lectures and labs, students are engaged in interactive seminars focused on discussion of clinical and research-based cases matched with normal histology and pathology…

  2. New insights into mycotoxin mixtures: The toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic

    Energy Technology Data Exchange (ETDEWEB)

    Alassane-Kpembi, Imourana [INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse (France); Université de Toulouse, ENVT, INP, UMR 1331 Toxalim, F-31076 Toulouse (France); Institut des Sciences Biomédicales Appliquées, Cotonou, Bénin (Benin); Kolf-Clauw, Martine; Gauthier, Thierry; Abrami, Roberta [INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse (France); Université de Toulouse, ENVT, INP, UMR 1331 Toxalim, F-31076 Toulouse (France); Abiola, François A. [Institut des Sciences Biomédicales Appliquées, Cotonou, Bénin (Benin); Oswald, Isabelle P., E-mail: Isabelle.Oswald@toulouse.inra.fr [INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse (France); Université de Toulouse, ENVT, INP, UMR 1331 Toxalim, F-31076 Toulouse (France); Puel, Olivier [INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse (France); Université de Toulouse, ENVT, INP, UMR 1331 Toxalim, F-31076 Toulouse (France)

    2013-10-01

    Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON < 15-ADON ≈ DON < NIV ≪ FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30–40%), mycotoxin combinations were synergistic; however DON–NIV–FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account. - Highlights: • We assessed the individual and combined cytotoxicity of five trichothecenes. • The tested concentrations correspond to the French consumer exposure levels. • The type of interaction in combined cytotoxicity varied with the effect level. • Low doses of Type B trichothecenes induced synergistic

  3. Interactions between urban heat islands and heat waves

    Science.gov (United States)

    Zhao, Lei; Oppenheimer, Michael; Zhu, Qing; Baldwin, Jane W.; Ebi, Kristie L.; Bou-Zeid, Elie; Guan, Kaiyu; Liu, Xu

    2018-03-01

    Heat waves (HWs) are among the most damaging climate extremes to human society. Climate models consistently project that HW frequency, severity, and duration will increase markedly over this century. For urban residents, the urban heat island (UHI) effect further exacerbates the heat stress resulting from HWs. Here we use a climate model to investigate the interactions between the UHI and HWs in 50 cities in the United States under current climate and future warming scenarios. We examine UHI2m (defined as urban-rural difference in 2m-height air temperature) and UHIs (defined as urban-rural difference in radiative surface temperature). Our results show significant sensitivity of the interaction between UHI and HWs to local background climate and warming scenarios. Sensitivity also differs between daytime and nighttime. During daytime, cities in the temperate climate region show significant synergistic effects between UHI and HWs in current climate, with an average of 0.4 K higher UHI2m or 2.8 K higher UHIs during HWs than during normal days. These synergistic effects, however, diminish in future warmer climates. In contrast, the daytime synergistic effects for cities in dry regions are insignificant in the current climate, but emerge in future climates. At night, the synergistic effects are similar across climate regions in the current climate, and are stronger in future climate scenarios. We use a biophysical factorization method to disentangle the mechanisms behind the interactions between UHI and HWs that explain the spatial-temporal patterns of the interactions. Results show that the difference in the increase of urban versus rural evaporation and enhanced anthropogenic heat emissions (air conditioning energy use) during HWs are key contributors to the synergistic effects during daytime. The contrast in water availability between urban and rural land plays an important role in determining the contribution of evaporation. At night, the enhanced release of stored

  4. Synergistic activity of letrozole and sorafenib on breast cancer cells.

    Science.gov (United States)

    Bonelli, Mara A; Fumarola, Claudia; Alfieri, Roberta R; La Monica, Silvia; Cavazzoni, Andrea; Galetti, Maricla; Gatti, Rita; Belletti, Silvana; Harris, Adrian L; Fox, Stephen B; Evans, Dean B; Dowsett, Mitch; Martin, Lesley-Ann; Bottini, Alberto; Generali, Daniele; Petronini, Pier Giorgio

    2010-11-01

    Estrogens induce breast tumor cell proliferation by directly regulating gene expression via the estrogen receptor (ER) transcriptional activity and by affecting growth factor signaling pathways such as mitogen-activated protein kinase (MAPK) and AKT/mammalian target of rapamycin Complex1 (mTORC1) cascades. In this study we demonstrated the preclinical therapeutic efficacy of combining the aromatase inhibitor letrozole with the multi-kinase inhibitor sorafenib in aromatase-expressing breast cancer cell lines. Treatment with letrozole reduced testosterone-driven cell proliferation, by inhibiting the synthesis of estrogens. Sorafenib inhibited cell proliferation in a concentration-dependent manner; this effect was not dependent on sorafenib-mediated inhibition of Raf1, but involved the down-regulation of mTORC1 and its targets p70S6K and 4E-binding protein 1 (4E-BP1). At concentrations of 5-10 μM the growth-inhibitory effect of sorafenib was associated with the induction of apoptosis, as indicated by release of cytochrome c and Apoptosis-Inducing Factor into the cytosol, activation of caspase-9 and caspase-7, and PARP-1 cleavage. Combination of letrozole and sorafenib produced a synergistic inhibition of cell proliferation associated with an enhanced accumulation of cells in the G(0)/G(1) phase of the cell cycle and with a down-regulation of the cell cycle regulatory proteins c-myc, cyclin D1, and phospho-Rb. In addition, longer experiments (12 weeks) demonstrated that sorafenib may be effective in preventing the acquisition of resistance towards letrozole. Together, these results indicate that combination of letrozole and sorafenib might constitute a promising approach to the treatment of hormone-dependent breast cancer.

  5. Synergistic Antimycobacterial Actions of Knowltonia vesicatoria (L.f Sims

    Directory of Open Access Journals (Sweden)

    Antoinette Labuschagné

    2012-01-01

    Full Text Available Euclea natalensis A.DC., Knowltonia vesicatoria (L.f Sims, and Pelargonium sidoides DC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract of K. vesicatoria was subjected to fractionation to identify the active compounds. The activity of the Knowltonia extract remained superior to the fractions with a minimum inhibitory concentration (MIC of 625.0 μg/mL against Mycobacterium smegmatis and an MIC of 50.00 μg/mL against M. tuberculosis. The K. vesicatoria extract was tested against two different drug-resistant strains of M. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination of K. vesicatoria with INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL. A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1 and 5-(hydroxymethylfuran-2(5H-one (2, were isolated from K. vesicatoria as the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1 was active against drug-sensitive M. tuberculosis with an MIC of 50.00 μg/mL.

  6. Microbial Reverse Electrodialysis Cells for Synergistically Enhanced Power Production

    KAUST Repository

    Kim, Younggy

    2011-07-01

    A new type of bioelectrochemical system for producing electrical power, called a microbial reverse-electrodialysis cell (MRC), was developed to increase voltages and power densities compared to those generated individually by microbial fuel cells (MFCs) or reverse electrodialysis (RED) systems. In RED systems, electrode overpotentials create significant energy losses due to thermodynamically unfavorable electrode reactions, and therefore a large number of stacked cells must be used to have significant energy recovery. This results in high capital costs for the large number of membranes, and increases energy losses from pumping water through a large number of cells. In an MRC, high overpotentials are avoided through oxidation of organic matter by exoelectrogenic bacteria on the anode and oxygen reduction on the cathode. An MRC containing only five pairs of RED cells, fed solutions typical of seawater (600 mM NaCl) and river water (12 mM NaCl) at 0.85 mL/min, produced up to 3.6 W/m2 (cathode surface area) and 1.2-1.3 V with acetate as a substrate. Pumping accounted for <2% of the produced power. A higher flow rate (1.55 mL/min) increased power densities up to 4.3 W/m2. COD removal was 98% with a Coulombic efficiency of 64%. Power production by the individual components was substantially lower with 0.7 W/m2 without salinity driven energy, and <0.015 W/m2 with reduced exoelectrogenic activity due to substrate depletion. These results show that the combination of an MFC and a RED stack synergistically increases performance relative to the individual systems, producing a new type of system that can be used to more efficiently capture salinity driven energy from seawater and river water. © 2011 American Chemical Society.

  7. The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides.

    Science.gov (United States)

    Pasay, Cielo; Arlian, Larry; Morgan, Marjorie; Gunning, Robin; Rossiter, Louise; Holt, Deborah; Walton, Shelley; Beckham, Simone; McCarthy, James

    2009-01-01

    Permethrin is the active component of topical creams widely used to treat human scabies. Recent evidence has demonstrated that scabies mites are becoming increasingly tolerant to topical permethrin and oral ivermectin. An effective approach to manage pesticide resistance is the addition of synergists to counteract metabolic resistance. Synergists are also useful for laboratory investigation of resistance mechanisms through their ability to inhibit specific metabolic pathways. To determine the role of metabolic degradation as a mechanism for acaricide resistance in scabies mites, PBO (piperonyl butoxide), DEF (S,S,S-tributyl phosphorotrithioate) and DEM (diethyl maleate) were first tested for synergistic activity with permethrin in a bioassay of mite killing. Then, to investigate the relative role of specific metabolic pathways inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST) and cytochrome P450 monooxygenase (cytochrome P450) activity in mite extracts. A statistically significant difference in median survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to median survival time of mites exposed to permethrin alone (presistant mites compared to sensitive mites. These findings indicate the potential utility of synergists in reversing resistance to pyrethroid-based acaricides and suggest a significant role of metabolic mechanisms in mediating pyrethroid resistance in scabies mites.

  8. In vitro evaluation of the interactions between acetone extracts of ...

    African Journals Online (AJOL)

    The effect of combinations of the acetone extract of Garcinia kola seeds and six first-line antibiotics was investigated by means of fractional inhibitory concentration (FIC) indices as well as by the use of time kill assays. Using the FIC indices, synergistic interactions were observed largely against gram positive organisms (FIC ...

  9. Drug interaction studies of Ximenia americana and Pavetta ...

    African Journals Online (AJOL)

    The therapeutic efficacy of single or multicomponent herbs is thought to reside in synergistic interactions between the bioactive constituents. The methanol extracts of X. americana and P. crassipes were initially screened against Gram positive and negative organisms as well as against Mycobacterium tuberculosis H37Rv ...

  10. Synergistic effect of gefitinib and rofecoxib in mesothelioma cells

    Directory of Open Access Journals (Sweden)

    Sacchi Ada

    2010-02-01

    Full Text Available Abstract Background Malignant mesothelioma (MM is an aggressive tumor that is resistant to conventional modes of treatment with chemotherapy, surgery or radiation. Research into the molecular pathways involved in the development of MM should yield information that will guide therapeutic decisions. Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2 are involved in the carcinogenesis of MM. Combination of COX-2 and EGFR inhibitors, therefore, could be an effective strategy for reducing cell growth in those lines expressing the two molecular markers. Results In order to verify the effect of COX-2 and EGFR inhibitors, five MM cell lines NCI-2452, MPP89, Ist-Mes-1, Ist-Mes-2 and MSTO-211 were characterized for COX-2 and EGFR and then treated with respective inhibitors (rofecoxib and gefitinib alone and in combination. Only MPP89, Ist-Mes-1 and Ist-Mes-2 were sensitive to rofecoxib and showed growth-inhibition upon gefitinib treatment. The combination of two drugs demonstrated synergistic effects on cell killing only in Ist-Mes-2, the cell line that was more sensitive to gefitinib and rofecoxib alone. Down-regulation of COX-2, EGFR, p-EGFR and up-regulation of p21 and p27 were found in Ist-Mes-2, after treatment with single agents and in combination. In contrast, association of two drugs resulted in antagonistic effect in Ist-Mes-1 and MPP89. In these cell lines after rofecoxib exposition, only an evident reduction of p-AKT was observed. No change in p-AKT in Ist-Mes-1 and MPP89 was observed after treatment with gefitinib alone and in combination with rofecoxib. Conclusions Gefitinib and rofecoxib exert cell type-specific effects that vary between different MM cells. Total EGFR expression and downstream signalling does not correlate with gefitinib sensitivity. These data suggest that the effect of gefitinib can be potentiated by rofecoxib in MM cell lines where AKT is not activated.

  11. Evaluation of the synergistic effects of milk proteins in a rapid viscosity analyzer.

    Science.gov (United States)

    Stephani, Rodrigo; Borges de Souza, Alisson; Leal de Oliveira, Marcone Augusto; Perrone, Ítalo Tuler; Fernandes de Carvalho, Antônio; Cappa de Oliveira, Luiz Fernando

    2015-12-01

    Protein systems (PS) are routinely used by companies from Brazil and around the globe to improve the texture, yield, and palatability of processed foods. Understanding the synergistic behavior among the different protein structures of these systems during thermal treatment under the influence of pH can help to better define optimum conditions for products and processes. The interpretation of the reactions and interactions that occur simultaneously among the protein constituents of these systems as dispersions during thermal processing is still a major challenge. Here, using a rapid viscosity analyzer, we observed the rheological changes in the startup viscosities of 5 PS obtained by combining varying proportions of milk protein concentrate and whey protein concentrate under different conditions of pH (5.0, 6.5, and 7.0) and heat processing (85°C/15min and 95°C/5min). The solutions were standardized to 25% of total solids and 17% of protein. Ten analytical parameters were used to characterize each of the startup-viscosity ramps for 35 experiments conducted in a 2×3 × 5 mixed planning matrix, using principal component analysis to interpret behavioral similarities. The study showed the clear influence of pH 5.5 in the elevation of the initial temperature of the PS startup viscosity by at least 5°C, as well as the effect of different milk protein concentrate:whey protein concentrate ratios above 15:85 at pH 7.0 on the viscographic profile curves. These results suggested that the primary agent driving the changes was the synergism among the reactions and interactions of casein with whey proteins during processing. This study reinforces the importance of the rapid viscosity analyzer as an analytical tool for the simulation of industrial processes involving PS, and the use of the startup viscosity ramp as a means of interpreting the interactions of system components with respect to changes related to the treatment temperature. Copyright © 2015 American Dairy Science

  12. A combination of trastuzumab and BAG-1 inhibition synergistically targets HER2 positive breast cancer cells.

    Science.gov (United States)

    Papadakis, Emmanouil; Robson, Natalia; Yeomans, Alison; Bailey, Sarah; Laversin, Stephanie; Beers, Stephen; Sayan, A Emre; Ashton-Key, Margaret; Schwaiger, Stefan; Stuppner, Hermann; Troppmair, Jakob; Packham, Graham; Cutress, Ramsey

    2016-04-05

    Treatment of HER2+ breast cancer with trastuzumab is effective and combination anti-HER2 therapies have demonstrated benefit over monotherapy in the neoadjuvant and metastatic settings. This study investigated the therapeutic potential of targeting the BAG-1 protein co-chaperone in trastuzumab-responsive or -resistant cells. In the METABRIC dataset, BAG-1 mRNA was significantly elevated in HER2+ breast tumors and predicted overall survival in a multivariate analysis (HR = 0.81; p = 0.022). In a breast cell line panel, BAG-1 protein was increased in HER2+ cells and was required for optimal growth as shown by siRNA knockdown. Overexpression of BAG-1S in HER2+ SKBR3 cells blocked growth inhibition by trastuzumab, whereas overexpression of a mutant BAG-1S protein (BAG-1S H3AB), defective in binding HSC70, potentiated the effect of trastuzumab. Injection of a Tet-On SKBR3 clone, induced to overexpress myc-BAG-1S into the mammary fat pads of immunocompromised mice, resulted in 2-fold larger tumors compared to uninduced controls. Induction of myc-BAG-1S expression in two Tet-On SKBR3 clones attenuated growth inhibition by trastuzumab in vitro. Targeting endogenous BAG-1 by siRNA enhanced growth inhibition of SKBR3 and BT474 cells by trastuzumab, while BAG-1 protein-protein interaction inhibitor (Thio-S or Thio-2) plus trastuzumab combination treatment synergistically attenuated growth. In BT474 cells this reduced protein synthesis, caused G1/S cell cycle arrest and targeted the ERK and AKT signaling pathways. In a SKBR3 subpopulation with acquired resistance to trastuzumab BAG-1 targeting remained effective and either Thio-2 or BAG-1 siRNA reduced growth more compared to trastuzumab-responsive parental cells. In summary, targeting BAG-1 function in combination with anti-HER2 therapy might prove beneficial.

  13. Synergistic cytotoxicity and mechanism of caffeine and lysozyme on hepatoma cell line HepG2

    Science.gov (United States)

    Yang, Hongchao; Li, Jingjuan; Cui, Lin; Ren, Yanqing; Niu, Liying; Wang, Xinguo; Huang, Yun; Cui, Lijian

    2018-03-01

    The influences of caffeine, lysozyme and the joint application of them on the hepatoma cell line HepG2 proliferation inhibition and cell apoptosis were observed by 3-(4, 5-dimethyl-2-thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and Hoechst 33342, which showed the proliferation inhibition rate of the joint application on HepG2 cells was 47.21%, significantly higher than caffeine or lysozyme, and the joint application promoted the apoptosis of HepG2 cells obviously. Van't Hoff classical thermodynamics formula, the Föster theory of non-radiation energy transfer and fluorescence phase diagram were used to manifest that the process of lysozyme binding to caffeine followed a two-state model, which was spontaneous at low temperature driven by enthalpy change, and the predominant intermolecular force was hydrogen bonding or Van der Waals force to stabilize caffeine-lysozyme complex with the distance 5.86 nm. The attenuated total reflection-Fourier transform infrared spectra indicated that caffeine decreased the relative contents of α-helix and β-turn, which inferred the structure of lysozyme tended to be "loose". Synchronous fluorescence spectra and ultraviolet spectra supported the above conclusion. The amino acid residues in the cleft of lysozyme were exposed and electropositivity was increased attributing to the loose structure, which were conducive to increasing caffeine concentration on the HepG2 cell surface by electrostatic interaction to show synergistic effect. The great quantities of microvilli on the liver cancer cell membrane surface, is beneficial for the lysozyme-caffeine compound to aggregate on cell surface to increase the concentration of caffeine to play stronger physiological role by electrostatic effect.

  14. New evaluation method of material degradation considering synergistic effects of radiation damage

    International Nuclear Information System (INIS)

    Miwa, Yukio; Kaji, Yoshiyuki; Okubo, Nariaki; Kondo, Keietsu; Tsukada, Takashi

    2008-01-01

    In core structural materials of next generation reactors such as a liquid-metal cooled fast breeding reactor and a supercritical-water cooled thermal or first reactor, materials' degradation behavior by neutron irradiation damage and thermal (cyclic) stress should be considered with fair accuracy in design process (including maintenance and repair plans), because the materials are used under higher temperature gradients and higher neutron flux fields than those in the present light water reactors. In the current experimental design rules, service lives of core structural components were determined by the materials degradation such as the increase of ductile-to-brittle transition temperature after post irradiation examination data. However, other materials degradations such as irradiation-assisted stress corrosion cracking (IASCC), which occurs by the degradation synergistically interacting with radiation hardening, local chemical composition change, swelling and radiation creep, should be considered reasonably in the design process of the next generation reactors, because of the anticipation of the beneficial effects by synergy of radiation damage. The radiation hardening and local chemical composition change at grain boundaries due to radiation-induced segregation increased with increasing dose. Above some threshold dose, swelling increased rapidly with increasing dose. Residual stress due to thermal stress and welding procedure decreased with increasing dose. To predict material failure by IASCC with reasonable accuracy, in this study, each material degradation phenomenon with different dose dependence was modeled with consideration of radiation induced stress relaxation. And then the models were integrated to simulate the failure behavior for the duration of reactor operation period. In this paper, the models obtained by ion-irradiation experiments and compared by data from neutron irradiation experiments were presented, and the concept of our new evaluation

  15. A coarse-grained model for synergistic action of multiple enzymes on cellulose

    Directory of Open Access Journals (Sweden)

    Asztalos Andrea

    2012-08-01

    Full Text Available Abstract Background Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates. Results We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose. Conclusions Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures

  16. Synergistic effects of coralyne and paclitaxel on cell migration and proliferation of breast cancer cells lines.

    Science.gov (United States)

    Kumari, Seema; Badana, Anil Kumar; Mohan, G Murali; Shailender Naik, G; Malla, RamaRao

    2017-07-01

    Breast cancer is one of the most frequently diagnosed cancer in woman. Triple-negative breast cancer (TNBC) is most aggressive form of breast cancer. There is a growing interest in the use of natural products in combinational chemotherapy to improve the effectiveness in combating proliferation of cancer cells. Here, we hypothesized that coralyne in combination with paclitaxel may exhibit synergistic effect on inhibition of proliferation, migration and induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines. MTT and BrdU incorporation assays were performed to study the effect of drugs alone and in combination on cell cytotoxicity and proliferation of the breast cancer cell lines, respectively. Adhesion and wound healing assays were performed to study the cell and extracellular matrix interactions. In addition, expression of proliferation marker ki-67 and apoptotic markers Bax and Bcl-2 was determined to study the effect of coralyne in combination with paclitaxel by reverse transcriptase PCR and confirmed by Western blot. The results indicated the synergism between coralyne and paclitaxel on proliferation and migration of breast cancer cell lines. This study also showed that combinational drug treatment decreased the expression of ki-67 and there was an increase in pro apoptotic factor Bax with decreased in expression of anti-apoptotic factor Bcl-2 in breast cancer cell lines with negligible effect on normal breast cell line. Overall, our data described the promising therapeutic potential of coralyne in combination with paclitaxel in treating breast cancer at lower effective dose. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Synergistic action of Galleria mellonella apolipophorin III and lysozyme against Gram-negative bacteria.

    Science.gov (United States)

    Zdybicka-Barabas, Agnieszka; Stączek, Sylwia; Mak, Paweł; Skrzypiec, Krzysztof; Mendyk, Ewaryst; Cytryńska, Małgorzata

    2013-06-01

    Insect immune response relies on the humoral and cellular mechanisms of innate immunity. The key factors are the antimicrobial polypeptides that act in concert against invading pathogens. Several such components, e.g. apolipophorin III (apoLp-III), lysozyme, and anionic peptide 2, are present constitutively in the hemolymph of non-challenged Galleria mellonella larvae. In the present study, we demonstrate an evidence for a synergistic action of G. mellonella lysozyme and apoLp-III against Gram-negative bacteria, providing novel insights into the mode of action of these proteins in insect antimicrobial defense. It was found that the muramidase activity of G. mellonella lysozyme considerably increased in the presence of apoLp-III. Moreover, apoLp-III enhanced the permeabilizing activity of lysozyme toward Escherichia coli cells. As shown using non-denaturing PAGE, the proteins did not form intermolecular complexes in vivo and in vitro, indicating that the effect observed was not connected with the intermolecular interactions between the proteins. Analysis of AFM images of E. coli cells exposed to G. mellonella lysozyme and/or apoLp-III revealed evident alterations in the bacterial surface structure accompanied by the changes in their biophysical properties. The bacterial cells demonstrated significant differences in elasticity, reflected by Young's modulus, as well as in adhesive forces and roughness values in comparison to the control ones. The constitutive presence of these two defense molecules in G. mellonella hemolymph and the fact that apoLp-III enhances lysozyme muramidase and perforating activities indicate that they can be regarded as important antibacterial factors acting at the early stage of infection against Gram-negative as well as Gram-positive bacteria. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Pathogenic mechanism in lung fibrosis. [Synergistic effects of BHT, O/sub 2/, and x rays in mice

    Energy Technology Data Exchange (ETDEWEB)

    Witschi, H.; Haschek, W. M.; Meyer, K. R.; Ullrich, R. L.; Dalbey, W. E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O/sub 2/ or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O/sub 2/ or x rays was synergistic. If exposure to O/sub 2/ or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed.

  19. Interactions of smoking with rs833061 polymorphism on the risk of non-alcoholic fat liver disease in Hubei Han population: a preliminary case–control study

    Directory of Open Access Journals (Sweden)

    Pengbo Wu

    2015-11-01

    Conclusion: The results indicated that both rs833061 and rs3025039 are associated with NAFLD risk. Furthermore, rs833061 is likely to have an interaction with smoking, and they have synergistic effects on risk of NAFLD in Hubei Han population.

  20. A synergistic effect of albumin and H₂O₂ accelerates corrosion of Ti6Al4V.

    Science.gov (United States)

    Yu, Fei; Addison, Owen; Davenport, Alison J

    2015-10-01

    The synergistic effect of albumin and H2O2 on corrosion of titanium alloy Ti6Al4V in physiological saline was investigated with long-term immersion tests and electrochemical methods. It was found that in the presence of both albumin and H2O2, the rate of metal release in immersion tests was far higher than in the presence of either species alone. Electrochemical polarisation curves and potentiostatic tests showed that H2O2 increased both the rates of the anodic and cathodic reactions, whilst albumin significantly decreased the rate of the cathodic reaction and slightly decreased the rate of the anodic reaction. The synergistic effect of albumin and H2O2 during immersion tests was attributed to the effect of adsorption of albumin in lowering the rate of the cathodic reaction and thus lowering the open circuit potential into the active region of titanium where complexation by H2O2 increased the corrosion rate. The corrosion attack was found to be greater in the β-phase of the alloy. The findings suggest that current standard tests in physiological or phosphate-buffered saline may underestimate the rate of corrosion in the peri-implant environment, in which albumin is the predominant protein, and reactive oxygen species such as H2O2 can occur as a result of inflammatory reactions in response to surgery, infection, or implant corrosion products. Corrosion of many biomedical implant materials occurs in the body leading to adverse biological responses. Several components of the environment into which a metal implant is placed including proteins and products of cellular physiology, been shown to modify corrosion resistance. Previously all studies on such components including the common protein albumin and the inflammatory product H2O2 have considered the effects of these species in isolation. For the first time we report a synergistic interaction between albumin and H2O2 significantly accelerating corrosion of Ti6Al4V at physiological pH and temperature. This is

  1. The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Jiang

    Full Text Available Renal dopamine D1-like receptors (D1R and D5R and the gastrin receptor (CCKBR are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake.

  2. Synergistic Success: The Power of Mentorship and Reaching the Senior Levels of the U.S. Army

    Science.gov (United States)

    2017-06-09

    SYNERGISTIC SUCCESS: THE POWER OF MENTORSHIP AND REACHING THE SENIOR LEVELS OF THE U.S. ARMY A thesis presented to the Faculty of...To) AUG 2016 – JUNE 2017 4. TITLE AND SUBTITLE Synergistic Success: The Power of Mentorship and Reaching the Senior Levels of the U.S. Army 5a...Synergistic Success: The Power of Mentorship and Reaching the Senior Levels of the U.S. Army Approved by: , Thesis Committee Chair Jack D

  3. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

    Directory of Open Access Journals (Sweden)

    Li-Xia Feng

    2014-03-01

    Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

  4. Synergistic antimicrobial activity of Camellia sinensis and Juglans regia against multidrug-resistant bacteria.

    Directory of Open Access Journals (Sweden)

    Amber Farooqui

    Full Text Available Synergistic combinations of antimicrobial agents with different mechanisms of action have been introduced as more successful strategies to combat infections involving multidrug resistant (MDR bacteria. In this study, we investigated synergistic antimicrobial activity of Camellia sinensis and Juglans regia which are commonly used plants with different antimicrobial agents. Antimicrobial susceptibility of 350 Gram-positive and Gram-negative strains belonging to 10 different bacterial species, was tested against Camellia sinensis and Juglans regia extracts. Minimum inhibitory concentrations (MICs were determined by agar dilution and microbroth dilution assays. Plant extracts were tested for synergistic antimicrobial activity with different antimicrobial agents by checkerboard titration, Etest/agar incorporation assays, and time kill kinetics. Extract treated and untreated bacteria were subjected to transmission electron microscopy to see the effect on bacterial cell morphology. Camellia sinensis extract showed higher antibacterial activity against MDR S. Typhi, alone and in combination with nalidixic acid, than to susceptible isolates." We further explore anti-staphylococcal activity of Juglans regia that lead to the changes in bacterial cell morphology indicating the cell wall of Gram-positive bacteria as possible target of action. The synergistic combination of Juglans regia and oxacillin reverted oxacillin resistance of methicillin resistant Staphylococcus aureus (MRSA strains in vitro. This study provides novel information about antimicrobial and synergistic activity of Camellia sinensis and Juglans regia against MDR pathogens.

  5. Synergistic effects of ethnomedicinal plants of Apocynaceae family and antibiotics against clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Chusri, Sasitorn; Siriyong, Thanyaluck; Na-Phatthalung, Pinanong; Voravuthikunchai, Supayang Piyawan

    2014-06-01

    To investigate the efficacy of 17 ethnomedicinal plants belonging to Apocynaceae family used in combination with 16 conventional antibiotics against non-multidrug resistant-, multidrug resistant (MDR)-, and extensive drug resistant (XDR) Acinetobacter baumannii (A. baumannii). Antibacterial activity and resistance modifying ability of 272 combinations were determined by growth inhibition assays and further confirmed by time-kill assay. Among the combinations of the antibiotics with Apocynaceae ethanol extracts on this pathogen, 15 (5%) had synergistic effects, 23 (8%) had partial synergistic effects and 234 (86%) had no effects. Synergistic activity was observed mostly when the Apocynaceae extracts were combined with rifampicin or cefazolin. Interestingly, 10 out of 17 combinations between the extracts and rifampicin displayed synergistic or partial synergistic behaviors. Holarrhena antidysenterica extract was additionally tested to restore rifampicin activity against clinical isolates of MDR and XDR A. baumannii. With respect to total or partial synergy, 70% was XDR A. baumannii isolates and 66% was MDR A. baumannii isolates. Holarrhena antidysenterica extract clearly demonstrated the ability to restore rifampicin activity against both A. baumannii ATCC19606 and clinically isolated A. baumannii. Additional studies examining its active principles as well as mechanisms of actions such as the effects on efflux pumps and outer membrane permeability alterations are recommended. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  6. Ellagitannins as synergists of ACV on the replication of ACV-resistant strains of HSV 1 and 2.

    Science.gov (United States)

    Vilhelmova-Ilieva, N; Jacquet, R; Quideau, S; Galabov, A S

    2014-10-01

    The plant-derived polyphenolic compounds castalagin, vescalagin and grandinin (C-glucosidic ellagitannins containing nonahydroxyterphenoyl) manifested a strong inhibitory effect on the replication of acyclovir-resistant strains of herpes simplex viruses (HSV) type 1 and 2 in MDBK cells in focus forming units (i.e., microscopically registered microplaques) reduction assay and in two variants of cytopathic effect inhibition test. The effect on the acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) strain was markedly higher compared to that on the ACV-resistant herpes simplex virus type 2 (HSV-2). The three compounds showed comparable levels of antiviral activity against ACV-resistant HSV strains, in contrast with previous results where castalagin exerted the highest degree of activity against wild type HSV strains (Vilhelmova et al., 2011). Combinations of ellagitannins and ACV were tested on the ACV-resistant strains of both HSV-1 and 2 and produced synergistic effects that were revealed by applying the three-dimensional approach of Prichard and Shipman (1990). The ellagitannin(s)-ACV combination applied against ACV-resistant HSV-1 produced a much stronger synergistic effect compared to the effect observed against ACV-resistant HSV-2. The study of the effects of the combination ellagitannin(s)-ACF on intact cell monolayers did not show any toxicity resulting from interaction between the two substances. Altogether, the results obtained in this study demonstrate the highly promising potential of these plant polyphenols as antiherpetic agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Synergistic effects of dietary nano selenium and vitamin C on growth, feeding, and physiological parameters of mahseer fish (Tor putitora

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Khan

    2017-02-01

    Full Text Available The current study was conducted to determine the synergistic effects of dietary nano selenium (Nano Se and vitamin C on growth, feeding, and physiological parameters of juvenile mahseer, Tor putitora. L-ascorbyl-2-polyphosphate (APP was used as a source of vitamin C. Four semi-purified experimental diets were prepared. A basal diet kept without the supplementation of any micronutrient and the other three diets were formulated such that three different levels of APP (100, 200, and 300 mg kg−1 were used in combination with a pre-determined dose of Nano Se (0.68 mg kg−1. The results showed that both the micronutrients positively synergized the effects of each other. APP at the rate of 300 mg kg−1 showed strong interaction with Nano Se. The APP300 + Nano Se0.68 mg kg−1 diet supplemented diet significantly decreased (P< 0.05 the feed conversion ratio (FCR while significantly increased (P< 0.05 the weight gain percentage (WG%, feed conversion efficiency (FCE%, specific growth rate (SGR, and serum growth hormone (GH concentration. Similarly, the physiological parameters such as red blood cells count (RBCs, hemoglobin level (Hb, hematocrit value (Hct, and serum lysozyme activity were also significantly increased in group of fish fed diet supplemented with APP100 mg kg−1 in combination with Nano Se0.68 mg kg−1 as compared to the control group. The present results clearly indicated the beneficent synergistic effects of Nano Se and APP in mahseer fish. Moreover, the current finding also supported our hypothesis that Nano Se and APP potentiate positively the effect of each other when both the micronutrients are supplemented together in the same fish feed.

  8. A study of the in vitro interaction of cotrimoxazole and ampicillin ...

    African Journals Online (AJOL)

    Synergistic interactions were recorded by the antibiotics against Staph. aureus and S. typhi while indifferent interaction occurred with P. aeruginosa. P. aeruginosa however, showed resistance to the two antibiotics when they were used alone. The implication is that cotrimoxazole and ampicillin can be used in combination ...

  9. Drug-Drug and Herb-Drug Interaction-A Comment | Esimone ...

    African Journals Online (AJOL)

    Clinically relevant drug-drug interactions may be pharmacodynamic or pharmacokinetic. And herbal medicinal products are becoming increasingly popular. Drug interactions can be in vivo or in vitro. Pharmacodynamic outcomes take such forms as Additive, Synergistic, Antagonistic or Indifferent. The paper reviews and ...

  10. Antileishmanial activity of semisynthetic lupane triterpenoids betulin and betulinic acid derivatives: synergistic effects with miltefosine.

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    Maria C Sousa

    Full Text Available Leishmaniasis is a neglected tropical disease (NTDs, endemic in 88 countries, affecting more than 12 million people. The treatment consists in pentavalent antimony compounds, amphotericin B, pentamidine and miltefosine, among others. However, these current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, it is important to continue the search for new effective and less toxic treatments. The anti-Leishmania activity of sixteen semisynthetic lupane triterpenoids derivatives of betulin (BT01 to BT09 and betulinic acid (AB10 to AB16 were evaluated. Drug interactions between the active compounds and one current antileishmanial drug, miltefosine, were assessed using the fixed ratio isobologram method. In addition, effects on the cell cycle, apoptosis/necrosis events, morphology and DNA integrity were studied. The derivatives BT06 (3β-Hydroxy-(20R-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate and AB13 (28-(1H-imidazole-1-yl-3,28-dioxo-lup-1,20(29-dien-2-yl-1H-imidazole-1-carboxylate were found to be the most active, with IC50 values of 50.8 µM and 25.8 µM, respectively. Interactions between these two compounds and miltefosine were classified as synergistic, with the most effective association being between AB13 and miltefosine, where decreases of IC50 values to 6 µM were observed, similar to the miltefosine activity alone. AB13 induced significant morphological changes, while both derivatives produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis/necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. In addition, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study has identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising

  11. Differential and Synergistic Functionality of Acylsugars in Suppressing Oviposition by Insect Herbivores.

    Directory of Open Access Journals (Sweden)

    Brian M Leckie

    original exudate. When these two fractions were recombined, the effect on both whiteflies and thrips exceeded the sum of the two fractions' effects, and was similar to that of the original exudate. These results suggest that increasing diversity of components within a mixture may increase suppression through synergistic interactions. This study demonstrates the potential for composition-specific deployment of acylsugars for herbivore oviposition suppression, either through in planta production by tomato lines, or as biocides applied by a foliar spray.

  12. Additive and Synergistic Impacts of Fishing and Warming on the Growth of a Temperate Marine Fish

    Science.gov (United States)

    Morrongiello, J.

    2016-02-01

    Fishing and climate change are having profound impacts on the trajectory and variability of marine populations. However, despite the wealth of work undertaken in marine environments on the causes of longer-term biological change, the effects of these two drivers have traditionally been considered in isolation or just additively. Such an approach obviously overlooks the potential for significant synergistic or antagonistic interactions between fishing and climate to occur. Indeed, it is increasingly becoming acknowledged that the direction and magnitude of biological responses to natural environmental variation and climate change can be mediated by other anthropogenic disturbances such as fishing, and vice versa. Somatic growth is an ideal candidate with which to explore the impacts of fishing and environmental variability due to its strong biological relevance and its heightened sensitivity to natural and anthropogenic drivers. I developed 19-year growth biochronologies (1980-1999) for three south-east Australian populations of a site-attached temperate reef fish, purple wrasse (Notolabrus fucicola) using individual-based growth information naturally archived in otoliths. A commercial wrasse fishery began in the early 1990s; before this there was negligible recreational or commercial fishing. The growth of older fish was proportionally higher and that of the youngest fish proportionally lower after the onset of commercial fishing; 2-year olds grew 7.4% slower, but 5-year-olds grew 10.3% and 10-year-olds 26% faster in the latter period. These results are consistent with a density dependent response to harvesting. Average growth rates across all ages increased by 6.6%.oC-1, reflecting either a direct or indirect temperature effect in this global marine 'hotspot'. Finally, the distribution of individual thermal reaction norms significantly changed post fishing, showing that fishing and temperature can have a synergetic impact on marine populations via within

  13. Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles.

    Science.gov (United States)

    Lu, Meng-Meng; Wang, Qiu-Jing; Chang, Zhi-Min; Wang, Zheng; Zheng, Xiao; Shao, Dan; Dong, Wen-Fei; Zhou, Yan-Min

    2017-01-01

    Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli . Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.

  14. TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation.

    Science.gov (United States)

    Zha, Li; He, Li; Liang, Yijian; Qin, Hui; Yu, Bin; Chang, Linli; Xue, Li

    2018-03-20

    Previous studies showed that inflammatory cytokines promote osteoclast formation, characterized by the function of bone resorption. However, it remains unclear whether inflammatory factors contribute to osteoporosis syndrome in postmenopausal women. Here, we found that postmenopausal women with osteoporosis (PO) had increased levels of TNF-α, compared with those without osteoporosis. TNF-α is highly correlated with the RANK and estrogen levels in PO patients. in vitro, TNF-α synergistically promotes RANKL-induced osteoclast formation by activation of NF-κB and PI3K/Akt signaling. Moreover, inhibition of PI3K/Akt totally blocked the synergistic effects of TNF-α on NF-κB activation as well as osteoclast formation. Together, these results demonstrate that TNF-α synergistically promotes RANKL-induced osteoclasts formation through activation of PI3K/Akt signaling, which ultimately contributes to osteoporosis syndrome in postmenopausal women. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. Synergistic effects of iron powder on intumescent flame retardant polypropylene system

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The effects of iron powder as a synergistic agent on the flame retardancy of intumescent flame retardant polypropylene composites (IFR-PP were studied. The thermogravimetric analysis (TGA and cone calorimeter (CONE were used to evaluate the synergistic effects of iron powder (Fe. The TGA data showed that Fe could enhance the thermal stability of the IFR-PP systems at high temperature and effectively increase the char residue formation. The CONE results revealed that Fe and IFR could clearly change the decomposition behavior of PP and form a char layer on the surface of the composites, consequently resulting in efficient reduction of the flammability parameters, such as heat release rate (HRR, mass loss (ML, Mass loss rate (MLR, total heat release (THR, carbon monoxide and so on. Thus, a suitable amount of Fe plays a synergistic effect in the flame retardancy of IFR composites.

  16. Antibacterial synergistic effect of chlorhexidine and hydrogen peroxide against Streptococcus sobrinus, Streptococcus faecalis and Staphylococcus aureus.

    Science.gov (United States)

    Steinberg, D; Heling, I; Daniel, I; Ginsburg, I

    1999-02-01

    Chlorhexidine (CHX) and Hydrogen peroxide (HP) are potent antibacterial agents that are used in controlling dental plaque. However, both agents bear undesired side-effects. We have tested the hypothesis that an antibacterial synergistic effect can occur between the two agents against Streptococcus sobrinus, Streptococcus faecalis and Staphylococcus aureus. We have found that at several combinations of HP and CHX an antibacterial synergistic effect does occur, while at other combinations a on-significant synergism was noticed. No antagonism between the two agents was found in our experimental system. It can be postulated that the mechanism of this synergistic effect is via alteration of the bacterial cell-surface by CHX thereby allowing for an increased amount of HP to penetrate and to react with the intercellular organelles of the bacteria. These results suggest that CHX and HP can be of use in controlling the dental plaque in the oral cavity.

  17. Synergistic impacts of deforestation, climate change and fire on the future biomes distribution in Amazonia

    Science.gov (United States)

    Sampaio, G.; Cardoso, M. F.; Nobre, C. A.; Salazar, L. F.

    2013-05-01

    Several studies indicate future increase of environmental risks for the ecosystems in the Amazon region as a result of climate and land-use change, and their synergistic interactions. Modeling studies (e.g. Oyama and Nobre 2004, Salazar et al. 2007, Malhi et al. 2008) project rapid and irreversible replacement of forests by savannas with large-scale losses of biodiversity and livelihoods for people in the region. This process is referred to as the Amazon Dieback, where accelerated plant mortality due to environmental changes lead to forest collapse and savannas expansion after "tipping points" in climate and land surface changes are achieved. In this study we performed new analyses to quantify how deforestation, climate change and fire may combine to affect the distribution of major biomes in Amazonia. Changes in land use consider deforestation scenarios of 0%, 20%, 40%, and 50% (Sampaio et al., 2007), with and without fires (Cardoso et al., 2008), under the two greenhouse gases scenarios B1 and A2 and three "representative concentration pathways" (RCPs): 2.6, 4.5 and 8.5, for years 2015-2034 and 2040-2059 ("2025" and "2050" time-slices), from IPCC AR4 and CMIP5. The results show that the area affected in scenarios A2 and RCP 8.5 is larger than in the climate scenario B1 and RCP 2.6, and in both cases the effect is progressively higher in time. Most important changes occur in the East and South of the Amazon, with replacement of tropical forest by seasonal forest and savanna. The effect of fire in this region is important in all scenarios. The Northwest Amazon presents the smallest changes in the area of tropical forest, indicating that even for substantial land-use modifications and global climate change, the resulting atmospheric conditions would still support tropical forest in the region. In summary, we conclude that the synergistic combination of deforestation, climate change resulting from global warming, and the potential for higher fire occurrence may lead

  18. Store-Operated Calcium Entry in Müller Glia Is Controlled by Synergistic Activation of TRPC and Orai Channels

    Science.gov (United States)

    Molnár, Tünde; Yarishkin, Oleg; Iuso, Anthony; Barabas, Peter; Jones, Bryan; Marc, Robert E.; Phuong, Tam T.T.

    2016-01-01

    The endoplasmic reticulum (ER) is at the epicenter of astrocyte Ca2+ signaling. We sought to identify the molecular mechanism underlying store-operated calcium entry that replenishes ER stores in mouse Müller cells. Store depletion, induced through blockade of sequestration transporters in Ca2+-free saline, induced synergistic activation of canonical transient receptor potential 1 (TRPC1) and Orai channels. Store-operated TRPC1 channels were identified by their electrophysiological properties, pharmacological blockers, and ablation of the Trpc1 gene. Ca2+ release-activated currents (ICRAC) were identified by ion permeability, voltage dependence, and sensitivity to selective Orai antagonists Synta66 and GSK7975A. Depletion-evoked calcium influx was initiated at the Müller end-foot and apical process, triggering centrifugal propagation of Ca2+ waves into the cell body. EM analysis of the end-foot compartment showed high-density ER cisternae that shadow retinal ganglion cell (RGC) somata and axons, protoplasmic astrocytes, vascular endothelial cells, and ER–mitochondrial contacts at the vitreal surface of the end-foot. The mouse retina expresses transcripts encoding both Stim and all known Orai genes; Müller glia predominantly express stromal interacting molecule 1 (STIM1), whereas STIM2 is mainly confined to the outer plexiform and RGC layers. Elimination of TRPC1 facilitated Müller gliosis induced by the elevation of intraocular pressure, suggesting that TRPC channels might play a neuroprotective role during mechanical stress. By characterizing the properties of store-operated signaling pathways in Müller cells, these studies expand the current knowledge about the functional roles these cells play in retinal physiology and pathology while also providing further evidence for the complexity of calcium signaling mechanisms in CNS astroglia. SIGNIFICANCE STATEMENT Store-operated Ca2+ signaling represents a major signaling pathway and source of cytosolic Ca2+ in

  19. Co-pyrolysis of waste newspaper with high-density polyethylene: Synergistic effect and oil characterization

    International Nuclear Information System (INIS)

    Chen, Weimin; Shi, Shukai; Zhang, Jun; Chen, Minzhi; Zhou, Xiaoyan

    2016-01-01

    Highlights: • Synergistic effect during co-pyrolysis occurred at 400–500 °C. • Oil yield from co-pyrolysis was increased by 31.59% compared to theoretical data. • Viscosity and T.A.N. of co-pyrolysis oil were decreased by 75.96% and 216.04%. • Synergistic effect was determined by altering the compounds content in derived oil. - Abstract: Biomass from waste newspaper (WP) was first co-pyrolyzed with high-density polyethylene (HDPE) in order to enhance the oil yield and its fuel properties. The synergistic effects during co-pyrolysis were investigated in terms of entire pyrolysis process, products yield and properties of liquid products (aqueous phase and oil phase) using thermogravimetric analysis coupled with infrared spectroscopy (TG-FTIR), physical properties analysis, elemental analysis, Fourier transform infrared spectroscopy (FT-IR), and gas chromatography/mass spectrometry (GC/MS). The results showed that synergistic effect occurred at 400–500 °C resulting in an obviously increase in oil phase by 31.59% as compared to theoretical data. Positive synergistic effects on fuel properties of co-pyrolysis oil were observed, especially demonstrating dramatically decrease in viscosity and total acid number by 75.96% and 216.04% in comparison to theoretical data. WP pyrolyzed alone gives mainly oxygenated compounds in its derived oil, while HDPE give hydrocarbons. No cross reaction products appeared in co-pyrolysis oil, implying that the synergistic effects were determined by altering its compounds content rather than generating cross reaction products. Unfortunately, aqueous phase and oil phase exhibit similar composition.

  20. The effect of insecticide synergists on the response of scabies mites to pyrethroid acaricides.

    Directory of Open Access Journals (Sweden)

    Cielo Pasay

    Full Text Available Permethrin is the active component of topical creams widely used to treat human scabies. Recent evidence has demonstrated that scabies mites are becoming increasingly tolerant to topical permethrin and oral ivermectin. An effective approach to manage pesticide resistance is the addition of synergists to counteract metabolic resistance. Synergists are also useful for laboratory investigation of resistance mechanisms through their ability to inhibit specific metabolic pathways.To determine the role of metabolic degradation as a mechanism for acaricide resistance in scabies mites, PBO (piperonyl butoxide, DEF (S,S,S-tributyl phosphorotrithioate and DEM (diethyl maleate were first tested for synergistic activity with permethrin in a bioassay of mite killing. Then, to investigate the relative role of specific metabolic pathways inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST and cytochrome P450 monooxygenase (cytochrome P450 activity in mite extracts. A statistically significant difference in median survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to median survival time of mites exposed to permethrin alone (p<0.0001. Incubation of mite homogenates with DEF showed inhibition of esterase activity (37%; inhibition of GST activity (73% with DEM and inhibition of cytochrome P450 monooxygenase activity (81% with PBO. A 7-fold increase in esterase activity, a 4-fold increase in GST activity and a 2-fold increase in cytochrome P450 monooxygenase activity were observed in resistant mites compared to sensitive mites.These findings indicate the potential utility of synergists in reversing resistance to pyrethroid-based acaricides and suggest a significant role of metabolic mechanisms in mediating pyrethroid resistance in scabies mites.

  1. In Situ Synthesis of Monomer Casting Nylon-6/Graphene-Polysiloxane Nanocomposites: Intercalation Structure, Synergistic Reinforcing, and Friction-Reducing Effect.

    Science.gov (United States)

    Li, Chengjie; Xiang, Meng; Zhao, Xiaowen; Ye, Lin

    2017-09-27

    On the basis of the industrialized graphene nanosheets (GNs) product, we synthesized monomer casting nylon-6 (MC PA6)/GN-3-aminopropyl-terminated poly(dimethylsiloxane) (APDMS) nanocomposite in situ through the anchoring effect of APDMS onto the GN surface. APDMS/PA6 molecules were confirmed to intercalate into the GN layers by the formation of strong interfacial interactions. The intercalation ratio and the average layer thickness of the grafted GN sample decreased in the presence of APDMS. Moreover, for MC PA6/GN-APDMS nanocomposite, GN-APDMS was uniformly distributed in the matrix and no phase separation was observed. The size of spherical APDMS particles was obviously reduced compared with that of MC PA6/APDMS composite, revealing a strong interaction between APDMS and GN and the enhancement of compatibility in the composite system. Compared with neat MC PA6, the addition of GN-APDMS resulted in 12% increase in the tensile strength and 37% increase in the impact strength; meanwhile, increase in both the storage modulus (E') and the glass transition temperature (T g ) indicated synergistic reinforcing and toughening effect of GN-APDMS on MC PA6. Furthermore, over 81 and 48% reduction in the friction coefficient and the specific wear rate, respectively, was achieved for the nanocomposite, and the worn surface displayed flat and smooth features with a uniform depth distribution, a low annealing effect, and a reduced friction heat, further confirming the synergistic friction-reducing effect of GN-APDMS on MC PA6.

  2. Germline Signaling Mediates the Synergistically Prolonged Longevity Produced by Double Mutations in daf-2 and rsks-1 in C. elegans

    Directory of Open Access Journals (Sweden)

    Di Chen

    2013-12-01

    Full Text Available Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor or RSKS-1 (S6K, key molecules in the insulin/IGF-1 signaling (IIS and target of rapamycin (TOR pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO via the AMP-activated protein kinase (AMPK complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms.

  3. In vitro synergistic antibacterial activity of Salvia officinalis L. and some preservatives

    Directory of Open Access Journals (Sweden)

    Stanojević Dragana

    2010-01-01

    Full Text Available The aim of this work was to investigate the antibacterial activity of aqueous extracts of the species Salvia officinalis L. and its synergistic action with the preservatives sodium nitrite, sodium benzoate and potassium sorbate in vitro against selected food spoiling bacteria. Synergism was assessed by the checkerboard assay method and quantitatively represented by the FIC index. Synergistic action was established for aqueous extract/sodium benzoate, aqueous extract/potassium sorbate, aqueous extract/sodium nitrite combinations. Synergism was detected in relation to: Agrobacterium tumefaciens, Bacillus subtilis and Proteus sp. Synergism was established at plant extract and preservative concentrations corresponding up to 1/8 MIC values.

  4. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells

    DEFF Research Database (Denmark)

    Byskov, A G; Fenger, M; Westergaard, L

    1993-01-01

    We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture...... in male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media...

  5. Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

    Directory of Open Access Journals (Sweden)

    Wu X

    2017-03-01

    Full Text Available Xiaozhe Wu,1 Zhan Li,1 Xiaolu Li,2,3 Yaomei Tian,1 Yingzi Fan,1 Chaoheng Yu,1 Bailing Zhou,1 Yi Liu,4 Rong Xiang,5 Li Yang1 1State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, 2International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 3Department of Plastic and Burn Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 4Department of Microbial Examination, Sichuan Center for Disease Control and Prevention, Chengdu, 5Nankai University School of Medicine, Tianjin, People’s Republic of China Abstract: Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001 and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin on clinical bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. The AZT-resistance genes (ermA, ermB, ermC, mefA, and msrA were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L. When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7–AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus

  6. Synergistic Processing of Biphenyl and Benzoate: Carbon Flow Through the Bacterial Community in Polychlorinated-Biphenyl-Contaminated Soil.

    Science.gov (United States)

    Leewis, Mary-Cathrine; Uhlik, Ondrej; Leigh, Mary Beth

    2016-02-26

    Aerobic mineralization of PCBs, which are toxic and persistent organic pollutants, involves the upper (biphenyl, BP) and lower (benzoate, BZ) degradation pathways. The activity of different members of the soil microbial community in performing one or both pathways, and their synergistic interactions during PCB biodegradation, are not well understood. This study investigates BP and BZ biodegradation and subsequent carbon flow through the microbial community in PCB-contaminated soil. DNA stable isotope probing (SIP) was used to identify the bacterial guilds involved in utilizing (13)C-biphenyl (unchlorinated analogue of PCBs) and/or (13)C-benzoate (product/intermediate of BP degradation and analogue of chlorobenzoates). By performing SIP with two substrates in parallel, we reveal microbes performing the upper (BP) and/or lower (BZ) degradation pathways, and heterotrophic bacteria involved indirectly in processing carbon derived from these substrates (i.e. through crossfeeding). Substrate mineralization rates and shifts in relative abundance of labeled taxa suggest that BP and BZ biotransformations were performed by microorganisms with different growth strategies: BZ-associated bacteria were fast growing, potentially copiotrophic organisms, while microbes that transform BP were oligotrophic, slower growing, organisms. Our findings provide novel insight into the functional interactions of soil bacteria active in processing biphenyl and related aromatic compounds in soil, revealing how carbon flows through a bacterial community.

  7. Dental biofilm: ecological interactions in health and disease.

    Science.gov (United States)

    Marsh, P D; Zaura, Egija

    2017-03-01

    The oral microbiome is diverse and exists as multispecies microbial communities on oral surfaces in structurally and functionally organized biofilms. To describe the network of microbial interactions (both synergistic and antagonistic) occurring within these biofilms and assess their role in oral health and dental disease. PubMed database was searched for studies on microbial ecological interactions in dental biofilms. The search results did not lend themselves to systematic review and have been summarized in a narrative review instead. Five hundred and forty-seven original research articles and 212 reviews were identified. The majority (86%) of research articles addressed bacterial-bacterial interactions, while inter-kingdom microbial interactions were the least studied. The interactions included physical and nutritional synergistic associations, antagonism, cell-to-cell communication and gene transfer. Oral microbial communities display emergent properties that cannot be inferred from studies of single species. Individual organisms grow in environments they would not tolerate in pure culture. The networks of multiple synergistic and antagonistic interactions generate microbial inter-dependencies and give biofilms a resilience to minor environmental perturbations, and this contributes to oral health. If key environmental pressures exceed thresholds associated with health, then the competitiveness among oral microorganisms is altered and dysbiosis can occur, increasing the risk of dental disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Modes of interactions between environmental drivers and marine biota

    Directory of Open Access Journals (Sweden)

    Philip eBoyd

    2015-02-01

    Full Text Available The responses of marine biota to global ocean change is characterised by multiple environmental drivers that interact to cause non-linear changes in organismal performance. Characterising interactions is critical for us to predict whether multiple drivers will accelerate or mitigate future biological responses. There is now a large body of evidence that drivers do not act independently, a common null model, but rather have synergistic or antagonistic effects on organisms. We review the literature on interactions among environmental drivers such as ocean acidification and warming, and identify three common modes of interaction: physicochemical interactions in the seawater media outside organisms, interactions that operate on organisms directly, for example by altering physiological rates; and interactions that occur through changes in ecosystems, like predation. Interactions can also occur across these levels increasing the number of permutations for interaction, and point to a diverse range of modes of interplay. Identifying the appropriate mode will help generalise interaction types to unstudied contexts.

  9. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid

    DEFF Research Database (Denmark)

    Meyer, Anne Merete Boye; Jacobsen, Charlotte Munch

    1996-01-01

    Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147.......Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147....

  10. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation

    DEFF Research Database (Denmark)

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PA beta N) was paired with iron chelators 2,2'-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically...

  11. A mechanistic study explaining the synergistic viscosity increase obtained from polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) in shotcrete

    Energy Technology Data Exchange (ETDEWEB)

    Pickelmann, J.; Plank, J., E-mail: sekretariat@bauchemie.ch.tum.de

    2012-11-15

    In shotcrete, a combination of polyethylene oxide (PEO) and {beta}-naphthalene sulfonate (BNS) is commonly applied to reduce rebound. Here, the mechanism for the synergistic viscosity increase resulting from this admixture combination was investigated via x-ray diffraction (XRD), infrared and nuclear magnetic resonance (NMR) spectroscopy. It was found that the electron-rich aromatic rings present in BNS donate electrons to the alkyl protons of PEO and thus increase the electron density there. This rare interaction is known as CH-{pi} interaction and leads to the formation of a supramolecular structure whereby PEO chains bind weakly to BNS molecules. Through this mechanism a polymer network exhibiting exceptionally high molecular weight and thus viscosity is formed. Among polycondensates, sulfanilic acid-phenol-formaldehyde (SPF) provides even higher synergy with PEO than BNS while melamine (PMS), acetone (AFS) or polycarboxylate (PCE) based superplasticizers do not work at all. Effectiveness of lignosulfonates is dependent on their degree of sulfonation.

  12. Study of the synergistic effects of salinity, pH, and temperature on the surface-active properties of biosurfactants produced by Lactobacillus pentosus.

    Science.gov (United States)

    Bello, Xanel Vecino; Devesa-Rey, Rosa; Cruz, José Manuel; Moldes, Ana Belén

    2012-02-08

    Many studies have investigated the effects of pH, temperature, and salinity on the surface-active properties of various surfactants, although in most cases the variables have been studied separately, without considering the effects of any interactions between them. In the present study, a Box-Behnken factorial design was applied to study the effects of pH, temperature, and salinity on the surface-active properties of a biosurfactant produced by Lactobacillus pentosus. The data obtained enabled development of a second-order model describing the interrelationships between operational and experimental variables, by equations including linear, interaction, and quadratic terms. The variable that had the greatest effect on the surface-active properties of the biosurfactant was pH. Moreover, at pH 3-5.5, decreases in salinity and temperature acted synergistically, reducing the surface tension of the biosurfactant; at pH 8, the same effect was observed with increasing salinity and temperature.

  13. Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing.

    Science.gov (United States)

    Ding, Jie; Kwan, Peter; Ma, Zengshuan; Iwashina, Takashi; Wang, Jianfei; Shankowsky, Heather A; Tredget, Edward E

    2016-09-01

    Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  14. Combinations of β-Lactam or Aminoglycoside Antibiotics with Plectasin Are Synergistic against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Hu, Yanmin; Liu, Alexander; Vaudrey, James; Vaiciunaite, Brigita; Moigboi, Christiana; McTavish, Sharla M.; Kearns, Angela; Coates, Anthony

    2015-01-01

    Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87–89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We

  15. Poly(I:C)-Encapsulating Nanoparticles Enhance Innate Immune Responses to the Tuberculosis Vaccine Bacille Calmette-Guérin (BCG) via Synergistic Activation of Innate Immune Receptors.

    Science.gov (United States)

    Speth, Martin T; Repnik, Urska; Müller, Elisabeth; Spanier, Julia; Kalinke, Ulrich; Corthay, Alexandre; Griffiths, Gareth

    2017-11-06

    The attenuated live vaccine strain bacille Calmette-Guérin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG's ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3), to enhance the immunogenicity of BCG in mouse bone marrow derived macrophages (BMDM) in vitro. Incorporation of poly(I:C) into NPs protected it against degradation by ribonucleases and increased its uptake by mouse BMDM. Whereas soluble poly(I:C) was ineffective, pIC-NPs strongly enhanced the proinflammatory immune response of BCG-infected macrophages in a synergistic fashion, as evident by increased production of cytokines and induction of nitric oxide synthesis. Using macrophages from mice deficient in key signaling molecules involved in the pathogen recognition response, we identified combined activation of MyD88- and TRIF-dependent TLR signaling pathways to be essential for the synergistic effect between BCG and NP. Moreover, synergy was strongly dependent on the order of the two stimuli, with TLR activation by BCG functioning as the priming event for the subsequent pIC-NP stimulus, which acted through an auto-/paracrine type I interferon (IFN) feedback loop. Our results provide a foundation for a promising new approach to enhance BCG-vaccine immunogenicity by costimulation with NPs. They also contribute to a molecular understanding of the observed synergistic interaction between the pIC-NPs and BCG vaccine.

  16. THE SYNERGISTIC SYLLABUS FOR TEACHING READING IN 32 TOURISM VOCATIONAL HIGH SCHOOL

    Directory of Open Access Journals (Sweden)

    Ahlis Qoidah Noor

    2017-12-01

    Full Text Available The new Syllabus at 2013 Curriculum for vocational high school created many problems to apply in the class. Based on the Need Analysis, the writer develops a Synergistic Syllabus for teaching Reading in vocational high school. It contains the syllabus combined from Task- Based Learning, Situational Syllabus, Program of International Student Assessment ( PISA item test and Character Building. It is a R and D research uses three phases of Observation, Developing and Try Out. It is in a True Experimental Research. The main findings are Reading Skill cannot be taught effectively for some reasons. There is no appropriate syllabus for teaching Reading; most teachers need some models in a syllabus. The results are the Synergistic Syllabus for teaching Reading, a set of Reading Material for Teaching Reading and a set of the lesson plan for one semester at Grade X of Tourism VHS. It is measured through mean, median and t- Test. To Sum up Synergistic Syllabus can develop many aspects, the systematic and meaningful activities in the class, motivation and good attitude. The standardized item of assignment, and a sense of competition in Reading activities and the Synergistic Syllabus assist teachers in teaching Reading using 2013 curriculum in the class effectively.

  17. Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

    International Nuclear Information System (INIS)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

    1983-01-01

    Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

  18. Writing throughout the Biochemistry Curriculum: Synergistic Inquiry-Based Writing Projects for Biochemistry Students

    Science.gov (United States)

    Mertz, Pamela; Streu, Craig

    2015-01-01

    This article describes a synergistic two-semester writing sequence for biochemistry courses. In the first semester, students select a putative protein and are tasked with researching their protein largely through bioinformatics resources. In the second semester, students develop original ideas and present them in the form of a research grant…

  19. Degradation by synergistic effect in synthetic insulators; Degradacion por efecto sinergico en aisladores sinteticos

    Energy Technology Data Exchange (ETDEWEB)

    Garza M, Anibal; Montesinos S, Jose I. [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1991-12-31

    A study is presented of the main degradation phenomena experimented by synthetic insulators and the simultaneous participation of such phenomena to propitiate a synergistic effect. [Espanol] Se presenta un estudio de los principales fenomenos de degradacion que sufren los aisladores sinteticos y la participacion simultanea de dichos fenomenos para propiciar un efecto sinergico.

  20. Synergistic effect of mixed neutron and gamma irradiation in bipolar operational amplifier OP07

    International Nuclear Information System (INIS)

    Yan, Liu; Wei, Chen; Shanchao, Yang; Xiaoming, Jin; Chaohui, He

    2016-01-01

    This paper presents the synergistic effects in bipolar operational amplifier OP07. The radiation effects are studied by neutron beam, gamma ray, and mixed neutron/gamma ray environments. The characterateristics of the synergistic effects are studied through comparison of different experiment results. The results show that the bipolar operational amplifier OP07 exhibited significant synergistic effects in the mixed neutron and gamma irradiation. The bipolar transistor is identified as the most radiation sensitive unit of the operational amplifier. In this paper, a series of simulations are performed on bipolar transistors in different radiation environments. In the theoretical simulation, the geometric model and calculations based on the Medici toolkit are built to study the radiation effects in bipolar components. The effect of mixed neutron and gamma irradiation is simulated based on the understanding of the underlying mechanisms of radiation effects in bipolar transistors. The simulated results agree well with the experimental data. The results of the experiments and simulation indicate that the radiation effects in the bipolar devices subjected to mixed neutron and gamma environments is not a simple combination of total ionizing dose (TID) effects and displacement damage. The data suggests that the TID effect could enhance the displacement damage. The synergistic effect should not be neglected in complex radiation environments.

  1. Synergistic effect of mixed neutron and gamma irradiation in bipolar operational amplifier OP07

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Liu, E-mail: liuyan@nint.ac.cn [State Key Laboratory of Intense Pulsed Irradiation Simulation and Effect, Northwest Institute of Nuclear Technology, P.O.Box 69-10, Xi’an 710024 (China); School of Nuclear Science and Technology, Xi’an Jiaotong University, Xi’an 710049 (China); Wei, Chen; Shanchao, Yang; Xiaoming, Jin [State Key Laboratory of Intense Pulsed Irradiation Simulation and Effect, Northwest Institute of Nuclear Technology, P.O.Box 69-10, Xi’an 710024 (China); Chaohui, He [School of Nuclear Science and Technology, Xi’an Jiaotong University, Xi’an 710049 (China)

    2016-09-21

    This paper presents the synergistic effects in bipolar operational amplifier OP07. The radiation effects are studied by neutron beam, gamma ray, and mixed neutron/gamma ray environments. The characterateristics of the synergistic effects are studied through comparison of different experiment results. The results show that the bipolar operational amplifier OP07 exhibited significant synergistic effects in the mixed neutron and gamma irradiation. The bipolar transistor is identified as the most radiation sensitive unit of the operational amplifier. In this paper, a series of simulations are performed on bipolar transistors in different radiation environments. In the theoretical simulation, the geometric model and calculations based on the Medici toolkit are built to study the radiation effects in bipolar components. The effect of mixed neutron and gamma irradiation is simulated based on the understanding of the underlying mechanisms of radiation effects in bipolar transistors. The simulated results agree well with the experimental data. The results of the experiments and simulation indicate that the radiation effects in the bipolar devices subjected to mixed neutron and gamma environments is not a simple combination of total ionizing dose (TID) effects and displacement damage. The data suggests that the TID effect could enhance the displacement damage. The synergistic effect should not be neglected in complex radiation environments.

  2. Synergistic Effect of Molybdate and Monoethanolamine on Corrosion Inhibition of Ductile Cast Iron in Tap Water

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. T.; Kim, Y. S. [Andong National University, Andong (Korea, Republic of); Chang, H. Y.; Lim, B. T.; Park, H. B. [KEPCO Engineering and Construction Company, Gimcheon (Korea, Republic of)

    2017-02-15

    A synergistic effect was observed in the combination of nitrite and ethanolamines. Ethanolamine is one of the representative organic corrosion inhibitors and can be categorized as adsorption type. However, nitrosamines can form when amines mix with sodium nitrite. Since nitrosamine is a carcinogen, the co-addition of nitrite and ethanolamine will be not practical, and thus, a non-toxic combination of inhibitors shall be needed. In order to maximize the effect of monoethanolamine, we focused on the addition of molybdate. Molybdate has been used to alternate the addition of chromate, but it showed insufficient oxidizing power relative to corrosion inhibitors. This work evaluated the synergistic effect of the co-addition of molybdate and monoethanolamine, and its corrosion mechanism was elucidated. A high concentration of molybdate or monoethanolamine was needed to inhibit the corrosion of ductile cast iron in tap water, but in the case of the co-addition of molybdate and monoethanolamine, a synergistic effect was observed. This synergistic effect could be attributed to the molybdate that partly oxidizes the metallic surface and the monoethanolamine that is simultaneously adsorbed on the graphite surface. This adsorbed layer then acts as the barrier layer that mitigates galvanic corrosion between the graphite and the matrix.

  3. Synergistic growth inhibition of cancer cells harboring the RET/PTC1 ...

    Indian Academy of Sciences (India)

    Synergistic growth inhibition of cancer cells harboring the RET/PTC1 oncogene by staurosporine and rotenone involves enhanced cell death. ANTÓNIO PEDRO GONÇALVES, ARNALDO VIDEIRA, VALDEMAR MÁXIMO and PAULA SOARES. J. Biosci. 36(4), September 2011, 639-648, © Indian Academy of Sciences.

  4. Revisiting the functional anatomy of the palmaris longus as a thenar synergist.

    Science.gov (United States)

    Moore, Colin W; Fanous, Jacob; Rice, Charles L

    2017-11-27

    Surgical studies describe the palmaris longus (PL) as a synergist in thumb abduction, which may facilitate its use in restoring thumb function using opponensplasty. However, beyond morphological descriptions and isometric thenar abduction strength measures, the evidence supporting the PL as a thenar synergist in-vivo is limited. The purpose here was to determine whether the PL provides synergistic contributions to thenar musculature by: (1) recording PL muscle activity using indwelling electromyography (EMG) during thumb movements; and (2) quantifying changes in PL muscle architecture using ultrasonography. In 10 healthy males, PL muscle activity was recorded during maximal thenar muscle contractions (abduction, flexion, opposition, adduction, and extension) with the wrist secured in a neutral position. The PL EMG was normalized to its maximal EMG recorded during isometric wrist flexion. Dynamic changes in PL muscle thickness (M T ) were determined during abduction and adduction using ultrasound imaging. The results indicate that the PL is activated during thenar movements with greatest relative PL EMG recorded during thenar abduction (46%), flexion (35%) and opposition (37%). Compared to rest, PL M T significantly increased (21%) during maximal thenar abduction. With direct measures in vivo, this study supports morphological and surgical observations indicating the PL acts as an extrinsic hand muscle in enhancing thenar muscle actions. Knowledge of the synergistic relationship between the PL and thenar musculature may allow for further development of surgical opponensplasty approaches using the abductor pollicis brevis and PL as a functional digastric unit. Clin. Anat, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    Directory of Open Access Journals (Sweden)

    Euna eOh

    2015-10-01

    Full Text Available The increasing resistance of Campylobacter to clinically-important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN. Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  6. SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

    DEFF Research Database (Denmark)

    Silva, Sonia; Altmannova, Veronika; Eckert-Boulet, Nadine

    2016-01-01

    for survival after genotoxic stress, it affects the outcome of recombination to promote conservative DNA repair. In some genetic assays, Rad52 and Rad59 SUMOylation act synergistically. Collectively, our data indicate that the described SUMO modifications affect the balance between conservative and non...

  7. Super absorbent conjugated microporous polymers: a synergistic structural effect on the exceptional uptake of amines.

    Science.gov (United States)

    Liu, Xiaoming; Xu, Yanhong; Guo, Zhaoqi; Nagai, Atsushi; Jiang, Donglin

    2013-04-21

    Conjugated microporous polymers exhibit a synergistic structural effect on the exceptional uptake of amines, whereas the dense porphyrin units facilitate uptake, the high porosity offers a large interface and the swellability boosts capacity. They are efficient in the uptake of both vapor and liquid amines, are applicable to various types of amines, and are excellent for cycle use.

  8. Synergistic extraction of thorium by β-hydroxy naphthaldoxime in presence of neutral donors

    International Nuclear Information System (INIS)

    Banerjee, S.; Biswas, S.; Basu, S.

    2001-01-01

    The effects of neutral organophosphorous compounds on the extraction of thorium by β-hydroxy naphthaldoxime in xylene are reported. Enhancement of the extraction is explained by a complex adduct formation in the organic phase. Synergistic coefficients and apparent formation constant of complex adducts are calculated. (author)

  9. Synergistic effects in mechanical properties of PLA/PCL blends with optimized composition, processing, and morphology

    Czech Academy of Sciences Publication Activity Database

    Ostafinska, Aleksandra; Fortelný, Ivan; Nevoralová, Martina; Hodan, Jiří; Kredatusová, Jana; Šlouf, Miroslav

    2015-01-01

    Roč. 5, č. 120 (2015), s. 98971-98982 ISSN 2046-2069 R&D Projects: GA ČR(CZ) GA14-17921S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : biodegradable poly mer blends * synergistic effects * impact strength Subject RIV: JJ - Other Materials Impact factor: 3.289, year: 2015

  10. Synergistic growth inhibition of cancer cells harboring the RET/PTC1 ...

    Indian Academy of Sciences (India)

    TPC-1 is a highly proliferative thyroid papillary carcinoma-derived cell line. These cells express the RET/PTC1 fusion protein, whose isoforms are characterized in this work. The bacterial alkaloid staurosporine and the plant extract rotenone are death-inducing drugs that have an inhibitory synergistic effect on the growth of ...

  11. Towards enhancing photocatalytic hydrogen generation: Which is more important, alloy synergistic effect or plasmonic effect?

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhenhe; Kibria, Md Golam; AlOtaibi, Bandar; Duchesne, Paul N.; Besteiro, Lucas V.; Gao, Yu; Zhang, Qingzhe; Mi, Zetian; Zhang, Peng; Govorov, Alexander O.; Mai, Liqiang; Chaker, Mohamed; Ma, Dongling

    2018-02-01

    Synergistic effect in alloys and plasmonic effect have both been explored for increasing the efficiency of water splitting. In depth understanding and comparison of their respective contributions in certain promising systems is highly desired for catalyst development, yet rarely investigated so far. We report herein our thorough investigations on a series of highly interesting nanocomposites composed of Pt, Au and C3N4 nanocomponents, which are designed to benefit from both synergistic and plasmonic effects. Detailed analyses led to an important conclusion that the contribution from the synergistic effect was at least 3.5 times that from the plasmonic effect in the best performing sample, Pt50Au50 alloy decorated C3N4. It showed remarkable turnover frequency of >1.6 mmol h-1 g-1 at room temperature. Our work provides physical insights for catalyst development by rationally designing samples to compare long-known synergistic effect with recently emerging, attractive plasmonic effect and represents the first case study in the field.

  12. Synergistic effects of some plant growth regulators on in vitro shoot ...

    African Journals Online (AJOL)

    The synergistic effects of some plant growth regulators was investigated upon shoot proliferation and growth of korarima (Aframomum corrorima (Braun) Jansen), an important culinary and medicinal plant species native to Ethiopia. Cultures were initiated from axillary bud explants of rhizome using Murashige and Skoog ...

  13. Esterase inhibition by synergists in the western flower thrips Frankliniella occidentalis.

    Science.gov (United States)

    López-Soler, Neus; Cervera, Amelia; Quinto, Vicente; Abellán, Jaime; Bielza, Pablo; Martínez-Pardo, Rafael; Garcerá, Maria Dolores

    2011-12-01

    Western flower thrips (WFT), Frankliniella occidentalis (Pergande), is among the most important crop pests in the south-eastern region of Spain. Its increasing resistance to insecticides constitutes a serious problem, and understanding the mechanisms involved is therefore of great interest. Use of synergists to inhibit the enzymes involved in insecticide detoxification is widely used to determine their responsibility for insecticide resistance. However, they do not always act as intended or expected, and caution must be exercised when interpreting synergist results. Laboratory-selected strains of WFT were used to analyse the effects of the synergists piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and methiocarb on total esterase activity. Significant differences were found, indicating esterase activity inhibition by DEF, a lower effect for methiocarb and a small inhibition of the activity by PBO. Esterase isoenzyme inhibition by these compounds showed a similar result; this assay revealed an extreme sensitivity of Triplet A (resistance-associated esterases) to DEF. In an in vivo assay carried out with these compounds at different incubation times, only DEF caused posterior in vitro esterase activity inhibition, with a maximum effect 1 h after treatment. In this work, only DEF shows true synergistic inhibition of WFT esterases. Copyright © 2011 Society of Chemical Industry.

  14. Evaluation of Antimycobacterial and Synergistic Activity of Plants Selected Based on Cheminformatic Parameters

    Science.gov (United States)

    Rahgozar, Nafise; Bakhshi Khaniki, Gholamreza; Sardari, Soroush

    2018-03-07

    Drug resistance is a major public health problem and a threat to progress made in bovine tuberculosis care and control worldwide. This study aimed at evaluating anti-mycobacterial and synergistic activity of some medicinal plants that were selected by cheminformatics studies against Mycobacterium bovis. Considering the strong synergistic antimycobacterial action of oleanolic acid in combination with tuberculosis drugs, NCBI database was explored to find the compounds with over 80% similarity to oleanolic acid, called S1. Plants containing S1-type compounds were traced to and resulted in five plants, including Datura stramonium, Boswellia serrata Lavandula stoechas, Rosmarinus officinalis, and Thymus vulgaris, as experimental samples. Crude extracts were prepared by percolation using 80% ethanol or as the product of a pharmaceutical company. The extracts were screened against Mycobacterium bovis using broth microdilution method and Alamar Blue Assay. Extracts from these plants were used in combination with isoniazid and ethambutol to investigate the possibility of synergy with respect to antimycobacterial activity. The extracts from D. stramonium, B. serrata a, L. stoechas, R. officinalis, and T. Thymus vulgaris showed antimycobacterial activity of 375, 125, 250, 187.5, 500 µg/ml, respectively. The best synergistic results were for L. stoechas and D. stramonium in combination with ethambutol, the fractional inhibitory concentration index was 0.125 µg/ml for both. The observed antimycobacterial and synergistic activities are completely novel and obtained from targeted screening designed according to cheminformatics strategy. As for the synergistic action of the extracts, they can be used as a supplement in bTB treatment.

  15. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    Science.gov (United States)

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  16. Synergistic approach for treatment of chicken coccidiosis using berberine--A plant natural product.

    Science.gov (United States)

    Malik, Tauseef Ahmad; Kamili, Azra N; Chishti, M Z; Tanveer, Syed; Ahad, Shazia; Johri, R K

    2016-04-01

    Despite the advent of anticoccidial drugs and vaccines, coccidiosis continues to result in substantial economic losses to the poultry industry. Berberine, a natural alkaloid is well known in studies involving synergistic approaches, thereby reducing the dosage of principal drugs. Therefore, a study was designed to see whether a synergistic anticoccidial effect could be obtained between amprolium and berberine, in vivo using broiler chicken. Anticoccidial activity was measured in comparison to the reference drug amprolium on the basis of oocyst output reduction, mean weight gain and feed conversion ratio. Oocyst output was measured using Mc-Masters counting technique. Different combinations of berberine and amprolium were tested and out of which 1:1 ratio was the most effective for controlling these parasites. Oral gavaging of 100(50 + 50) mg/kg body weight of 1:1 ratio of amprolium and berberine caused the equivalent reduction in number of oocysts (38.85 ± 9.61) one day prior to that of standard drug amprolium (49.95 ± 16.65) as well as pure berberine (44.4 ± 9.61) used in the study. Weight gain of birds was also highest in the