WorldWideScience

Sample records for cross-disciplinary mode-of-action based

  1. Curriculum Development for Technology-Based Entrepreneurship Education: A Cross-Disciplinary and Cross-Cultural Approach

    Science.gov (United States)

    Kazakeviciute, Agne; Urbone, Renata; Petraite, Monika

    2016-01-01

    University-based entrepreneurship education is facing a paradigm shift between the classical "business school" and the contemporary cross-disciplinary "technology venturing" approach, mainly advocated by engineering schools and other communities outside business schools. The conflict is between structured "business…

  2. Goal-Based Domain Modeling as a Basis for Cross-Disciplinary Systems Engineering

    Science.gov (United States)

    Jarke, Matthias; Nissen, Hans W.; Rose, Thomas; Schmitz, Dominik

    Small and medium-sized enterprises (SMEs) are important drivers for innovation. In particular, project-driven SMEs that closely cooperate with their customers have specific needs in regard to information engineering of their development process. They need a fast requirements capture since this is most often included in the (unpaid) offer development phase. At the same time, they need to maintain and reuse the knowledge and experiences they have gathered in previous projects extensively as it is their core asset. The situation is complicated further if the application field crosses disciplinary boundaries. To bridge the gaps and perspectives, we focus on shared goals and dependencies captured in models at a conceptual level. Such a model-based approach also offers a smarter connection to subsequent development stages, including a high share of automated code generation. In the approach presented here, the agent- and goal-oriented formalism i * is therefore extended by domain models to facilitate information organization. This extension permits a domain model-based similarity search, and a model-based transformation towards subsequent development stages. Our approach also addresses the evolution of domain models reflecting the experiences from completed projects. The approach is illustrated with a case study on software-intensive control systems in an SME of the automotive domain.

  3. Exploring the Modes of Action of Phosphorus-Based Flame Retardants in Polymeric Systems

    Directory of Open Access Journals (Sweden)

    Sebastian Rabe

    2017-04-01

    Full Text Available Phosphorus-based flame retardants were incorporated into different, easily preparable matrices, such as polymeric thermoset resins and paraffin as a proposed model for polyolefins and investigated for their flame retardancy performance. The favored mode of action of each flame retardant was identified in each respective system and at each respective concentration. Thermogravimetric analysis was used in combination with infrared spectroscopy of the evolved gas to determine the pyrolysis behavior, residue formation and the release of phosphorus species. Forced flaming tests in the cone calorimeter provided insight into burning behavior and macroscopic residue effects. The results were put into relation to the phosphorus content to reveal correlations between phosphorus concentration in the gas phase and flame inhibition performance, as well as phosphorus concentration in the residue and condensed phase activity. Total heat evolved (fire load and peak heat release rate were calculated based on changes in the effective heat of combustion and residue, and then compared with the measured values to address the modes of action of the flame retardants quantitatively. The quantification of flame inhibition, charring, and the protective layer effect measure the non-linear flame retardancy effects as functions of the phosphorus concentration. Overall, this screening approach using easily preparable polymer systems provides great insight into the effect of phosphorus in different flame retarded polymers, with regard to polymer structure, phosphorus concentration, and phosphorus species.

  4. Designing a CTSA-Based Social Network Intervention to Foster Cross-Disciplinary Team Science.

    Science.gov (United States)

    Vacca, Raffaele; McCarty, Christopher; Conlon, Michael; Nelson, David R

    2015-08-01

    This paper explores the application of network intervention strategies to the problem of assembling cross-disciplinary scientific teams in academic institutions. In a project supported by the University of Florida (UF) Clinical and Translational Science Institute, we used VIVO, a semantic-web research networking system, to extract the social network of scientific collaborations on publications and awarded grants across all UF colleges and departments. Drawing on the notion of network interventions, we designed an alteration program to add specific edges to the collaboration network, that is, to create specific collaborations between previously unconnected investigators. The missing collaborative links were identified by a number of network criteria to enhance desirable structural properties of individual positions or the network as a whole. We subsequently implemented an online survey (N = 103) that introduced the potential collaborators to each other through their VIVO profiles, and investigated their attitudes toward starting a project together. We discuss the design of the intervention program, the network criteria adopted, and preliminary survey results. The results provide insight into the feasibility of intervention programs on scientific collaboration networks, as well as suggestions on the implementation of such programs to assemble cross-disciplinary scientific teams in CTSA institutions. © 2015 Wiley Periodicals, Inc.

  5. [Construction and mode of action of a suction apparatus based on the vacuum cleaner principle].

    Science.gov (United States)

    Ehmer, D

    1975-03-01

    Design and mode of action of a suction apparatus worked on the vacuum cleaner principle. A suction apparatus worked on the vacuum cleaner principle is presented as a part of a modern work-place conception.

  6. Biological mode of action of a nitrophenolates-based biostimulant: case study.

    Science.gov (United States)

    Przybysz, Arkadiusz; Gawrońska, Helena; Gajc-Wolska, Janina

    2014-01-01

    The challenges facing modern plant production involve (i) responding to the demand for food and resources of plant origin from the world's rapidly growing population, (ii) coping with the negative impact of stressful conditions mainly due to anthropopressure, and (iii) meeting consumers' new requirements and preferences for food that is high in nutritive value, natural, and free from harmful chemical additives. Despite employing the most modern plant cultivation technologies and the progress that has been made in breeding programs, the genetically-determined crop potential is still far from being fully exploited. Consequently yield and quality are often reduced, making production less, both profitable and attractive. There is an increasing desire to reduce the chemical input in agriculture and there has been a change toward integrated plant management and sustainable, environmentally-friendly systems. Biostimulants are a category of relatively new products of diverse formulations that positively affect a plant's vital processes and whose impact is usually more evident under stressful conditions. In this paper, information is provided on the mode of action of a nitrophenolates-based biostimulant, Atonik, in model species and economically important crops grown under both field and controlled conditions in a growth chamber. The effects of Atonik on plant morphology, physiology, biochemistry (crops and model plant) and yield and yield parameters (crops) is demonstrated. Effects of other biostimulants on studied in this work processes/parameters are also presented in discussion.

  7. Biological mode of action of a nitrophenolates-based biostimulant: Case study

    Directory of Open Access Journals (Sweden)

    Arkadiusz ePrzybysz

    2014-12-01

    Full Text Available The challenges facing modern plant production involve (i responding to the demand for food and resources of plant origin from the world’s rapidly growing population, (ii coping with the negative impact of stressful conditions mainly due to anthropopressure, and (iii meeting consumers’ new requirements and preferences for food that is high in nutritive value, natural, and free from harmful chemical additives.Despite employing the most modern plant cultivation technologies and the progress that has been made in breeding programs, the genetically-determined crop potential is still far from being fully exploited. Consequently yield and quality are often reduced, making production less, both profitable and attractive. There is an increasing desire to reduce the chemical input in agriculture and there has been a change towards integrated plant management and sustainable, environmentally-friendly systems. Biostimulants are a category of relatively new products of diverse formulations that positively affect a plant’s vital processes and whose impact is usually more evident under stressful conditions. In this paper, information is provided on the mode of action of a nitrophenolates-based biostimulant, Atonik, in model species and economically important crops grown under both field and controlled conditions in a growth chamber. The effects of Atonik on plant morphology, physiology, biochemistry (crops and model plant and yield and yield parameters (crops is demonstrated. Effects of other biostimulants on studied in this work processes/parameters are also presented in discussion.

  8. Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping.

    Science.gov (United States)

    De Abrew, K Nadira; Kainkaryam, Raghunandan M; Shan, Yuqing K; Overmann, Gary J; Settivari, Raja S; Wang, Xiaohong; Xu, Jun; Adams, Rachel L; Tiesman, Jay P; Carney, Edward W; Naciff, Jorge M; Daston, George P

    2016-06-01

    Connectivity mapping is a method used in the pharmaceutical industry to find connections between small molecules, disease states, and genes. The concept can be applied to a predictive toxicology paradigm to find connections between chemicals, adverse events, and genes. In order to assess the applicability of the technique for predictive toxicology purposes, we performed gene array experiments on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen, clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate, flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1α,25-dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic acid, progesterone, RU486, ketoconazole, valproic acid, desferrioxamine, amoxicillin, 6-aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1-naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at the 6-, 24-, and 48-hour time points for 3 different concentrations in the 4 cell lines: MCF7, Ishikawa, HepaRG, and HepG2 GEO (super series accession no.: GSE69851). The 34 chemicals were grouped in to predefined mode of action (MOA)-based chemical classes based on current literature. Connectivity mapping was used to find linkages between each chemical and between chemical classes. Cell line-specific linkages were compared with each other and to test whether the method was platform and user independent, a similar analysis was performed against publicly available data. The study showed that the method can group chemicals based on MOAs and the inter-chemical class comparison alluded to connections between MOAs that were not predefined. Comparison to the publicly available data showed that the method is user and platform independent. The results provide an example of an alternate data analysis process for high-content data, beneficial for predictive toxicology, especially when grouping chemicals for read across

  9. Cross Disciplinary Biometric Systems

    CERN Document Server

    Liu, Chengjun

    2012-01-01

    Cross disciplinary biometric systems help boost the performance of the conventional systems. Not only is the recognition accuracy significantly improved, but also the robustness of the systems is greatly enhanced in the challenging environments, such as varying illumination conditions. By leveraging the cross disciplinary technologies, face recognition systems, fingerprint recognition systems, iris recognition systems, as well as image search systems all benefit in terms of recognition performance.  Take face recognition for an example, which is not only the most natural way human beings recognize the identity of each other, but also the least privacy-intrusive means because people show their face publicly every day. Face recognition systems display superb performance when they capitalize on the innovative ideas across color science, mathematics, and computer science (e.g., pattern recognition, machine learning, and image processing). The novel ideas lead to the development of new color models and effective ...

  10. Implications of dibenzyl trisulphide for disease treatment based on its mode of action.

    Science.gov (United States)

    Williams, L A D; Barton, E N; Kraus, W; Rösner, H

    2009-11-01

    Studies conducted on the secondary metabolite (natural product), dibenzyl trisulphide (DTS), which was isolated from the sub-tropical shrub Petiveria alliacea (guinea hen weed, anamu) [Phytolaccaceae] have shown tremendous pharmaceutical promise as a drug prototype. This is now reflected in the development of the broad spectrum anti-cancer molecule, fluorapacin (bis(4-fluorobenzyl) trisulphide) which has an excellent safety profile. The mode of action elucidated for DTS is the mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases ERK 1 and ERK 2). The MAPKinase signal transduction biochemical pathways are important in the regulation of a wide range of cellular processes which are important in disease establishment. These processes include: cancer cell proliferation, nerve repair, memory enhancement, autoimmune diseases, which are linked to thymic cell involution and bone marrow functions, cerebrovascular and cardiovascular diseases. In addition to the MAPkinase signal transduction mode of action, DTS also prevents the denaturation of serum albumin which is a feature of nonsteroidal anti-inflammatory drugs, thus supporting the molecule's possible role in the treatment of inflammatory ageing diseases.

  11. Evidence-based modeling of mode-of-action for functional ingredients influencing Alzheimer’s disease through neurotrophin pathway

    Directory of Open Access Journals (Sweden)

    Erfan Younesi

    2014-08-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF is the most widely expressed member of the neurotrophin family in the human brain and is crucially involved in the development of neural circuits, modulation of synaptic plasticity, and regulation of cognitive functions, including learning and memory. Many studies have shown the association of altered BDNF levels with neurodegenerative and neuropsychiatric disorders. However, BDNF is not able to cross the blood-brain barrier and, thus, its delivery to the nervous system is a challenge. Therefore, functional diets with the ability to induce production of BDNF in the brain may offer an alternative route. The objective of this study was three-fold: first, to find out diets that are causally linked to the agonistic activity of BDNF in the neurotrophin signaling pathway; second and mainly, to investigate mode-of-action of these functional diets through systems-based mechanistic modeling in the context of Alzheimer’s disease; and third, to demonstrate the proof-of-concept application of systems biology methods, that are well established in the pharmaceutical sector, to the emerging field of functional food. Methods: In the first step, two cause-and-effect models of BDNF signaling in two states, i.e. normal state and Alzheimer’s disease state, were constructed using published knowledge in scientific literature and pathway databases. A “differential model analysis” between the two states was performed by which mechanistic mode-of-action of BDNF in neurotrophin signaling pathway could be explained with a high molecular resolution in both normal and disease states. The BDNF mode-of-action model was further validated using the “biomarkerguided validation” approach. In the second step, scientific evidence on the effect of various functional diets on BDNF levels and BDNF-related biological processes or outcomes was harvested from biomedical literature using a disease-specific semantic search

  12. Achieving generic competences through a cross-disciplinary research based course in Arctic Technology

    DEFF Research Database (Denmark)

    Kirkelund, Gunvor Marie; Hansen, Claus Thorp; Jensen, Pernille Erland

    2014-01-01

    successful in achieving both the scientific and generic competences than the students who did not. The students evaluate the course as being highly motivating for further learning and they get confident by successfully having executed a research based project in a new context. The project and field work...... engineering competences, so they are more aware of this, instead of just focussing on improving their scientific competences.......In a research based course in Arctic Technology, different teaching activities were used to support learning of both technical and generic competences. The active learning was based around a 3-weeks field work period in Greenland in combination with lectures, assignments, project and peer group...

  13. Interprofessional Clinical Ethics Education: The Promise of Cross-Disciplinary Problem-Based Learning.

    Science.gov (United States)

    Kurtz, Melissa J; Starbird, Laura E

    2016-09-01

    A review of Lin et al.'s pilot study exploring the effects of an interprofessional, problem-based learning clinical ethics curriculum on Taiwanese medical and nursing students' attitudes towards interprofessional collaboration highlights the benefits of interprofessional collaboration and offers insight into how problem-based learning might be universally applied in ethics education. Interprofessional collaboration is an ideal approach for exploring ethical dilemmas because it involves all relevant professionals in discussions about ethical values that arise in patient care. Interprofessional ethics collaboration is challenging to implement, however, given time constraints and organizational and practice demands. Nevertheless, we suggest that when professionals collaborate, they can collectively express greater commitment to the patient. We also suggest future research avenues that can explore additional benefits of interprofessional collaboration in clinical ethics. © 2016 American Medical Association. All Rights Reserved.

  14. Marine neurotoxins: state of the art, bottlenecks, and perspectives for mode of action based methods of detection in seafood.

    Science.gov (United States)

    Nicolas, Jonathan; Hendriksen, Peter J M; Gerssen, Arjen; Bovee, Toine F H; Rietjens, Ivonne M C M

    2014-01-01

    Marine biotoxins can accumulate in fish and shellfish, representing a possible threat for consumers. Many marine biotoxins affect neuronal function essentially through their interaction with ion channels or receptors, leading to different symptoms including paralysis and even death. The detection of marine biotoxins in seafood products is therefore a priority. Official methods for control are often still using in vivo assays, such as the mouse bioassay. This test is considered unethical and the development of alternative assays is urgently required. Chemical analyses as well as in vitro assays have been developed to detect marine biotoxins in seafood. However, most of the current in vitro alternatives to animal testing present disadvantages: low throughput and lack of sensitivity resulting in a high number of false-negative results. Thus, there is an urgent need for the development of new in vitro tests that would allow the detection of marine biotoxins in seafood products at a low cost, with high throughput combined with high sensitivity, reproducibility, and predictivity. Mode of action based in vitro bioassays may provide tools that fulfil these requirements. This review covers the current state of the art of such mode of action based alternative assays to detect neurotoxic marine biotoxins in seafood. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Comparing the mode of action of intraocular lutein-based dyes with synthetic dyes.

    Science.gov (United States)

    Sousa-Martins, Diogo; Caseli, Luciano; Figueiredo, Mafalda C; Sa E Cunha, Claudia; Mota-Filipe, Helder; Souza-Lima, Acácio; Belfort, Rubens; Rodrigues, Eduardo; Maia, Mauricio

    2015-02-19

    To investigate and compare the mechanism by which lutein-based and synthetic intraocular dyes interact with their target membranes during ophthalmic surgeries. Surrogate membrane models were used in order to simulate the different intraocular membranes: internal limiting membrane (ILM), vitreous, anterior capsule (AC), and epiretinal membrane (ERM). Different lutein-based dyes, such as Phacodyne, Retidyne, Retidyne Plus, and Vitreodyne were tested, as well as Trypan Blue (TB), Indocyanine Green (ICG), Brilliant Blue (BB), and Triamcinolone Acetonide (TA). The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). With the exception of TA and ICG, none of the tested dyes revealed toxicity to the analyzed membranes. The interaction of TA with the vitreous model affected deeply the biointerface structure of the model. A significant condensation of the monolayer is noted when ICG contacted with ILM by the isotherms or even a solubilization of part of the monolayer toward the aqueous subphase. Retidyne Plus may provide the fluidization of the membrane, but maintains intact the structure of proteins present in the model. The present study demonstrates for the first time that lutein-based dyes interact through a physical mechanism of action with membrane models of structures present in human eye. On the other hand, the chemical interaction of synthetic dyes TA and ICG resulted in an alteration of the membrane models. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  16. Science and Technology Text Mining: Cross-Disciplinary Innovation

    Science.gov (United States)

    2003-07-14

    1 SCIENCE AND TECHNOLOGY TEXT MINING : CROSS-DISCIPLINARY INNOVATION BY DR. RONALD N. KOSTOFF OFFICE OF NAVAL RESEARCH ARLINGTON, VA 22217 PHONE: 703...696-4198 FAX: 703-696-4274 INTERNET: kostofr@onr.navy.mil KEYWORDS: Innovation; text mining ; literature-based discovery; clustering; workshops; cross...TO) xx-xx-1999 to xx-xx-2003 4. TITLE AND SUBTITLE SCIENCE AND TECHNOLOGY TEXT MINING CROSS-DISCIPLINARY INNOVATION Unclassified 5a. CONTRACT NUMBER

  17. A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.

    Science.gov (United States)

    De Abrew, K Nadira; Overmann, Gary J; Adams, Rachel L; Tiesman, Jay P; Dunavent, John; Shan, Yuqing K; Carr, Gregory J; Daston, George P; Naciff, Jorge M

    2015-02-03

    High-content data have the potential to inform mechanism of action for toxicants. However, most data to support this notion have been generated in vivo. Because many cell lines and primary cells maintain a differentiated cell phenotype, it is possible that cells grown in culture may also be useful in predictive toxicology via high-content approaches such as whole-genome microarray. We evaluated global changes in gene expression in primary rat hepatocytes exposed to two concentrations of ten hepatotoxicants: acetaminophen (APAP), β-naphthoflavone (BNF), chlorpromazine (CPZ), clofibrate (CLO), bis(2-ethylhexyl)phthalate (DEHP), diisononyl phthalate (DINP), methapyrilene (MP), valproic acid (VPA), phenobarbital (PB) and WY14643 at two separate time points. These compounds were selected to cover a range of mechanisms of toxicity, with some overlap in expected mechanism to address the question of how predictive gene expression analysis is, for a given mode of action. Gene expression microarray analysis was performed on cells after 24h and 48h of exposure to each chemical using Affymetrix microarrays. Cluster analysis suggests that the primary hepatocyte model was capable of responding to these hepatotoxicants, with changes in gene expression that appear to be mode of action-specific. Among the different methods used for analysis of the data, a combination method that used pathways (MOAs) to filter total probesets provided the most robust analysis. The analysis resulted in the phthalates clustering closely together, with the two other peroxisome proliferators, CLO and WY14643, eliciting similar responses at the whole-genome and pathway levels. The Cyp inducers PB, MP, CPZ and BNF also clustered together. VPA and APAP had profiles that were unique. A similar analysis was performed on externally available (TG-GATES) in vivo data for 6 of the chemicals (APAP, CLO, CPZ, MP, MP and WY14643) and compared to the in vitro result. These results indicate that transcription

  18. Inhibition of Listeria monocytogenes on Ready-to-Eat Meats Using Bacteriocin Mixtures Based on Mode-of-Action

    Directory of Open Access Journals (Sweden)

    Paul Priyesh Vijayakumar

    2017-03-01

    Full Text Available Bacteriocin-producing (Bac+ lactic acid bacteria (LAB comprising selected strains of Lactobacillus curvatus, Lactococcus lactis, Pediococcus acidilactici, and Enterococcus faecium and thailandicus were examined for inhibition of Listeria monocytogenes during hotdog challenge studies. The Bac+ strains, or their cell-free supernatants (CFS, were grouped according to mode-of-action (MOA as determined from prior studies. Making a mixture of as many MOAs as possible is a practical way to obtain a potent natural antimicrobial mixture to address L. monocytogenes contamination of RTE meat products (i.e., hotdogs. The heat resistance of the bacteriocins allowed the use of pasteurization to eliminate residual producer cells for use as post-process surface application or their inclusion into hotdog meat emulsion during cooking. The use of Bac+ LAB comprising 3× MOAs directly as co-inoculants on hotdogs was not effective at inhibiting L. monocytogenes. However, the use of multiple MOA Bac+ CFS mixtures in a variety of trials demonstrated the effectiveness of this approach by showing a >2-log decrease of L. monocytogenes in treatment samples and 6–7 log difference vs. controls. These data suggest that surface application of multiple mode-of-action bacteriocin mixtures can provide for an Alternative 2, and possibly Alternative 1, process category as specified by USDA-FSIS for control of L. monocytogenes on RTE meat products.

  19. Relationship between acute and chronic toxicity for prevalent organic pollutants in Vibrio fischeri based upon chemical mode of action.

    Science.gov (United States)

    Wang, Xiao H; Fan, Ling Y; Wang, Shuo; Wang, Yue; Yan, Li C; Zheng, Shan S; Martyniuk, Christopher J; Zhao, Yuan H

    2017-09-15

    Chemicals show diverse modes of action (MOAs) in aquatic organisms depending upon acute and chronic toxicity evaluations. Here, toxicity data for Vibrio fischeri involving 52 compounds for acute and chronic toxicity were used to determine the congruence of acute and chronic toxicity for assessing MOAs. Using toxic ratios, most of the compounds categorized into MOAs that included baseline, less inert or reactive compounds with acute toxicity were also categorized as baseline, less inert or reactive compounds with chronic toxicity. However, significantly different toxic effects were observed with acute and chronic toxicity for the reactive and specific-acting compounds. The acute-chronic toxic ratios were smaller and less variable for the baseline and less inert compounds, but were greater and more variable for the reactive and specific-acting compounds. Baseline and less inert compounds share same MOAs, but reactive and specific-acting compounds have different MOAs between acute and chronic toxicity. Bioconcentration processes cannot reach an equilibrium for highly hydrophilic and ionized compounds with short-term exposure, resulting in lower toxicity compared to long-term exposure. Pronounced differences for the antibiotics were not only due to the difference in bioconcentration, but also due to a predicted difference in MOAs during acute and chronic exposures. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Cross-Disciplinary Collaboration and Learning

    Directory of Open Access Journals (Sweden)

    Deana D. Pennington

    2008-12-01

    Full Text Available Complex environmental problem solving depends on cross-disciplinary collaboration among scientists. Collaborative research must be preceded by an exploratory phase of collective thinking that creates shared conceptual frameworks. Collective thinking, in a cross-disciplinary setting, depends on the facility with which collaborators are able to learn and understand each others' perspectives. This paper applies three perspectives on learning to the problem of enabling cross-disciplinary collaboration: Maslow's hierarchy of needs, constructivism, and organizational learning. Application of learning frameworks to collaboration provides insights regarding receptive environments for collaboration, and processes that facilitate cross-disciplinary interactions. These environments and interactions need time to develop and require a long phase of idea generation preceding any focused research effort. The findings highlight that collaboration is itself a complex system of people, scientific theory, and tools that must be intentionally managed. Effective management of the system requires leaders who are facilitators and are capable of orchestrating effective environments and interactions.

  1. Evaluating Aquatic invertebrate vulnerability to insecticides based on intrinsic sensitivuty, biological traits, and toxic mode of action

    NARCIS (Netherlands)

    Rico, A.; Brink, van den P.J.

    2015-01-01

    In the present study, the authors evaluated the vulnerability of aquatic invertebrates to insecticides based on their intrinsic sensitivity and their population-level recovery potential. The relative sensitivity of invertebrates to 5 different classes of insecticides was calculated at the genus,

  2. Proteomic analysis of food borne pathogens following the mode of action of the disinfectants based on pyridoxal oxime derivatives.

    Science.gov (United States)

    Šrajer Gajdošik, Martina; Andjelković, Uroš; Gašo-Sokač, Dajana; Pavlović, Hrvoje; Shevchuk, Olga; Martinović, Tamara; Clifton, James; Josić, Djuro

    2017-09-01

    A comprehensive proteomic analysis of food borne pathogens after treatment with disinfectants based on ammonium salts of pyridinium oxime was performed. Changes in proteomes of the Gram-positive bacterium Bacillus subtilis and the Gram-negative one, Escherichia coli, were evaluated. Up and down-regulated proteins in these bacteria after growth under the inhibition with four different disinfectants based on chloride and bromide salts of pyridinium oxime were identified and their cellular localizations and functions were determined by gene ontology searching. Proteome changes presented here demonstrate different mechanisms of action of these disinfectants. In the Gram-positive food pathogen Bacillus subtilis, the inhibitory substances seem to act mainly at the cell surface and cause significant alterations of membrane and cell surface proteins. On the other hand, intracellular proteins were more affected in the Gram-negative pathogen Escherichia coli. This research is a contribution to the investigation of the virulence and pathogenicity of food borne bacteria and their survival under stress conditions, and can also lead the way for further development of new inhibitors of microbial growth and studies of mechanism of their actions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action

    Science.gov (United States)

    Willett, Catherine; Rae, Jessica Caverly; Goyak, Katy O.; Minsavage, Gary; Westmoreland, Carl; Andersen, Melvin; Avigan, Mark; Duché, Daniel; Harris, Georgina; Hartung, Thomas; Jaeschke, Hartmut; Kleensang, Andre; Landesmann, Brigitte; Martos, Suzanne; Matevia, Marilyn; Toole, Colleen; Rowan, Andrew; Schultz, Terry; Seed, Jennifer; Senior, John; Shah, Imran; Subramanian, Kalyanasundaram; Vinken, Mathieu; Watkins, Paul

    2016-01-01

    Summary A workshop sponsored by the Human Toxicology Project Consortium (HTPC), “Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action” brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered. PMID:24535319

  4. Soil Governance: Accessing Cross-Disciplinary Perspectives

    Directory of Open Access Journals (Sweden)

    Tanya Marjoram Howard

    2015-01-01

    Full Text Available Soil provides the foundation for agricultural and environmental systems, and are subject to a complex governance regime of property rights and secondary impacts from industry and domestic land use. Complex natural resource management issues require approaches to governance that acknowledge uncertainty and complexity. Theories of next generation environmental governance assume that inclusion of diverse perspectives will improve reform directions and encourage behaviour change. This paper reports on a qualitative survey of an international workshop that brought together cross-disciplinary perspectives to address the challenges of soil governance. Results reveal the challenges of communicating effectively across disciplines. The findings suggest that strategies for improved soils governance must focus on increasing communications with community stakeholders and engaging land managers in designing shared governance regimes. The need for more conscious articulation of the challenges of cross-disciplinary environments is discussed and strategies for increasing research collaboration in soils governance are suggested. The identified need for more systematic approaches to cross-disciplinary learning, including reporting back of cross-disciplinary initiatives to help practitioners learn from past experience, forms part of the rationale for this paper.

  5. Cross-disciplinary consumer citizenship education

    DEFF Research Database (Denmark)

    Nielsen, Sanne Schnell; Gottschau, Jette

    2005-01-01

    This paper examines a cross-disciplinary, problem-oriented workshop dealing with consumer issues. The workshop forms part of the four-year Danish teacher training course offered by the Copenhagen Day and Evening College of Teacher Training. The workshop covers issues related to civic, environmental...... these competences in their practical teaching of consumer citizenship education in Danish comprehensive schools. Comprehensive schools are state schools combining primary and lower secondary education. In Denmark, teacher training includes 24 weeks of teaching practice. The workshop forms an integral part...... and methods function. In addition, they are offered a visit by their college supervisor. Upon completion of the teaching practice, a plenary evaluation takes place at the teacher training college. This is intended to bring the lessons learned during the practicum into the classroom in order to share...

  6. Mode of action of mosquito repellents

    Science.gov (United States)

    The mode of action of mosquito repellents remains a controversial topic. However, electrophysiological studies and molecular approaches have provided a better understanding of how repellents exert their effects. Here, we briefly discuss various notions of repellent action and present the current sta...

  7. NASA's Platform for Cross-Disciplinary Microchannel Research

    Science.gov (United States)

    Son, Sang Young; Spearing, Scott; Allen, Jeffrey; Monaco, Lisa A.

    2003-01-01

    A team from the Structural Biology group located at the NASA Marshall Space Flight Center in Huntsville, Alabama is developing a platform suitable for cross-disciplinary microchannel research. The original objective of this engineering development effort was to deliver a multi-user flight-certified facility for iterative investigations of protein crystal growth; that is, Iterative Biological Crystallization (IBC). However, the unique capabilities of this facility are not limited to the low-gravity structural biology research community. Microchannel-based research in a number of other areas may be greatly accelerated through use of this facility. In particular, the potential for gas-liquid flow investigations and cellular biological research utilizing the exceptional pressure control and simplified coupling to macroscale diagnostics inherent in the IBC facility will be discussed. In conclusion, the opportunities for research-specific modifications to the microchannel configuration, control, and diagnostics will be discussed.

  8. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Improvement of Plasticity of Ti-Based Bulk Metallic Glasses by Addition of Nb

    Science.gov (United States)

    Shan, Sheng-Feng; Zhan, Zai-Ji; Fan, Chang-Zeng; Jia, Yuan-Zhi; Zhang, Bao-Qing; Liu, Ri-Ping; Wang, Wen-Kui

    2008-11-01

    Ti-based bulk metallic glasses (Ti4oZr25Cu9Ni8Be18)100-xNbx with x = 0 to 5at.% are prepared by copper-mold casting. The glass formation ability is almost unchanged by addition of Nb. The compression plasticity is, however, apparently changed, from 3% at x = 0 to 13% at x = 3, about 330% increases at the strain rate of 1 × 10-4s-1. The increment of the plasticity can be attributed to the segregation of Nb in the area of shear bands during the compression processing. An effective way to increase the plasticity of Ti-based bulk metallic glasses is thus proposed.

  9. Volcanic Supersites as cross-disciplinary laboratories

    Science.gov (United States)

    Provenzale, Antonello; Beierkuhnlein, Carl; Giamberini, Mariasilvia; Pennisi, Maddalena; Puglisi, Giuseppe

    2017-04-01

    Volcanic Supersites, defined in the frame of the GEO-GSNL Initiative, are usually considered mainly for their geohazard and geological characteristics. However, volcanoes are extremely challenging areas from many other points of view, including environmental and climatic properties, ecosystems, hydrology, soil properties and biogeochemical cycling. Possibly, volcanoes are closer to early Earth conditions than most other types of environment. During FP7, EC effectively fostered the implementation of the European volcano Supersites (Mt. Etna, Campi Flegrei/Vesuvius and Iceland) through the MED-SUV and FUTUREVOLC projects. Currently, the large H2020 project ECOPOTENTIAL (2015-2019, 47 partners, http://www.ecopotential-project.eu/) contributes to GEO/GEOSS and to the GEO ECO Initiative, and it is devoted to making best use of remote sensing and in situ data to improve future ecosystem benefits, focusing on a network of Protected Areas of international relevance. In ECOPOTENTIAL, remote sensing and in situ data are collected, processed and used for a better understanding of the ecosystem dynamics, analysing and modelling the effects of global changes on ecosystem functions and services, over an array of different ecosystem types, including mountain, marine, coastal, arid and semi-arid ecosystems, and also areas of volcanic origin such as the Canary and La Reunion Islands. Here, we propose to extend the network of the ECOPOTENTIAL project to include active Volcanic Supersites, such as Mount Etna and other volcanic Protected Areas, and we discuss how they can be included in the framework of the ECOPOTENTIAL workflow. A coordinated and cross-disciplinary set of studies at these sites should include geological, biological, ecological, biogeochemical, climatic and biogeographical aspects, as well as their relationship with the antropogenic impact on the environment, and aim at the global analysis of the volcanic Earth Critical Zone - namely, the upper layer of the Earth

  10. Ten simple rules for a successful cross-disciplinary collaboration

    DEFF Research Database (Denmark)

    Knapp, Bernhartd; Bardenet, Rémi; Bernabeu, Miguel O

    2015-01-01

    Cross-disciplinary collaborations have become an increasingly important part of science. They are seen as a key factor for finding solutions to pressing societal challenges on a global scale including green technologies, sustainable food production and drug development. This has also been realized......, igniting and successfully maintaining cross-disciplinary collaborations can be a delicate task. In this article we focus on the specific challenges associated with cross-disciplinary research in particular from the perspective of the theoretician. As research fellows of the 2020 Science project (http......://www.2020science.net) and collaboration partners, we bring broad experience of developing interdisciplinary collaborations [2–12]. We intend this guide for early career computational researchers as well as more senior scientists who are entering a cross disciplinary setting for the first time. We describe...

  11. Modes of action of anthelmintic drugs.

    Science.gov (United States)

    Martin, R J

    1997-07-01

    Modes of action of anthelmintic drugs are described. Some anthelmintic drugs act rapidly and selectively on neuromuscular transmission of nematodes. Levamisole, pyrantel and morantel are agonists at nicotinic acetylcholine receptors of nematode muscle and cause spastic paralysis. Dichlorvos and haloxon are organophosphorus cholinesterase antagonists. Piperazine is a GABA (gamma-amino-butyric acid) agonist at receptors on nematode muscles and causes flaccid paralysis. The avermectins increase the opening of glutamate-gated chloride (GluCl) channels and produce paralysis of pharyngeal pumping. Praziquantel has a selective effect on the tegument of trematodes and increases permeability of calcium. Other anthelmintics have a biochemical mode of action. The benzimidazole drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke, and inhibit microtubule formation. The salicylanilides: rafoxanide, oxyclozanide, brotianide and closantel and the substituted phenol, nitroxynil, are proton ionophores. Clorsulon is a selective antagonist of fluke phosphoglycerate kinase and mutase. Diethylcarbamazine blocks host, and possibly parasite, enzymes involved in arachidonic acid metabolism, and enhances the innate, nonspecific immune system.

  12. Cross-disciplinary Science and the Structure of Scientific Perspectives

    DEFF Research Database (Denmark)

    Alrøe, Hugo Fjelsted; Noe, Egon

    2014-01-01

    Cross-disciplinary use of science is needed to solve complex, real-world problems, but carrying out scientific research with multiple very different disciplines is in itself a non-trivial problem. Perspectives matter. In this paper we carry out a philosophical analysis of the perspectival nature...... of science, focusing on the synchronic structure of scientific perspectives across disciplines and not on the diachronic, historical structure of shifting perspectives within single disciplines that has been widely discussed since Kuhn and Feyerabend. We show what kinds of cross-disciplinary disagreement...... to expect due to the perspectival structure of science, suggest how to handle different scientific perspectives in cross-disciplinary work through perspectives of a second order, and discuss some fundamental epistemic differences between different types of science....

  13. Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-05-11

    A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p

  14. Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6.

    Directory of Open Access Journals (Sweden)

    Angela Corona

    Full Text Available The DNA polymerase and ribonuclease H (RNase H activities of human immunodeficiency virus type 1 (HIV-1 are needed for the replication of the viral genome and are validated drug targets. However, there are no approved drugs inhibiting RNase H and the efficiency of DNA polymerase inhibitors can be diminished by the presence of drug resistance mutations. In this context, drugs inhibiting both activities could represent a significant advance towards better anti-HIV therapies. We report on the mechanisms of allosteric inhibition of a newly synthesized isatin-based compound designated as RMNC6 that showed IC50 values of 1.4 and 9.8 μM on HIV-1 RT-associated RNase H and polymerase activities, respectively. Blind docking studies predict that RMNC6 could bind two different pockets in the RT: one in the DNA polymerase domain (partially overlapping the non-nucleoside RT inhibitor [NNRTI] binding pocket, and a second one close to the RNase H active site. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. In addition, despite being naturally resistant to NNRTIs, the polymerase activity of HIV-1 group O RT was efficiently inhibited by RMNC6. The compound was also an inhibitor of the RNase H activity of wild-type HIV-1 group O RT, although we observed a 6.5-fold increase in the IC50 in comparison with the prototypic HIV-1 group M subtype B enzyme. Mutagenesis studies showed that RT RNase H domain residues Asn474 and Tyr501, and in a lesser extent Ala502 and Ala508, are critical for RMNC6 inhibition of the endonuclease activity of the RT, without affecting its DNA polymerization activity. Our results show that RMNC6 acts as a dual inhibitor with allosteric sites in the DNA polymerase and the RNase H domains of HIV-1 RT.

  15. Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6.

    Science.gov (United States)

    Corona, Angela; Meleddu, Rita; Esposito, Francesca; Distinto, Simona; Bianco, Giulia; Masaoka, Takashi; Maccioni, Elias; Menéndez-Arias, Luis; Alcaro, Stefano; Le Grice, Stuart F J; Tramontano, Enzo

    2016-01-01

    The DNA polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) are needed for the replication of the viral genome and are validated drug targets. However, there are no approved drugs inhibiting RNase H and the efficiency of DNA polymerase inhibitors can be diminished by the presence of drug resistance mutations. In this context, drugs inhibiting both activities could represent a significant advance towards better anti-HIV therapies. We report on the mechanisms of allosteric inhibition of a newly synthesized isatin-based compound designated as RMNC6 that showed IC50 values of 1.4 and 9.8 μM on HIV-1 RT-associated RNase H and polymerase activities, respectively. Blind docking studies predict that RMNC6 could bind two different pockets in the RT: one in the DNA polymerase domain (partially overlapping the non-nucleoside RT inhibitor [NNRTI] binding pocket), and a second one close to the RNase H active site. Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6. In addition, despite being naturally resistant to NNRTIs, the polymerase activity of HIV-1 group O RT was efficiently inhibited by RMNC6. The compound was also an inhibitor of the RNase H activity of wild-type HIV-1 group O RT, although we observed a 6.5-fold increase in the IC50 in comparison with the prototypic HIV-1 group M subtype B enzyme. Mutagenesis studies showed that RT RNase H domain residues Asn474 and Tyr501, and in a lesser extent Ala502 and Ala508, are critical for RMNC6 inhibition of the endonuclease activity of the RT, without affecting its DNA polymerization activity. Our results show that RMNC6 acts as a dual inhibitor with allosteric sites in the DNA polymerase and the RNase H domains of HIV-1 RT.

  16. Innovative sport technology through cross-disciplinary research ...

    African Journals Online (AJOL)

    This paper provides an overview of the advantages and disadvantages of innovative sport technology brought about by cross-disciplinary research in sport, engineering, medical and material sciences. Sport technology has subsequently contributed greatly to the enhancement of epidemiology, prevention and management ...

  17. Lonergan's philosophy as grounding for cross-disciplinary research.

    Science.gov (United States)

    Kane, Anne

    2014-04-01

    Increasingly, nurses conduct scientific inquiry into complex health-care problems by collaborating on teams with researchers from other highly specialized fields. As cross-disciplinary research proliferates and becomes institutionalized globally, researchers will increasingly encounter the need to integrate their particular research perspectives within inquiries without sacrificing the potential contributions of their discipline-specific expertise. The work of the philosopher Bernard Lonergan (1904–1984) offers the necessary philosophical grounding. Here, I defend a role for philosophy in cross-disciplinary research and present selected ideas in Lonergan's work. These include: (1) a dynamic, normative pattern that each inquirer operates uniquely also forms the common core, or unity, in knowing; (2) the possibility of cross-disciplinary knowledge development is dependent on each researcher's consciousness of her or his attentiveness, intelligence, reasonableness, and responsibleness; and (3) shifts in researchers' viewpoints, or horizons, facilitate their collaborative inquiry and their grasp of the unity in knowing. The desire to know, shared by team members, drives their inquiry. Lonergan's stance is consistent with nursing values because it respects, but does not unconditionally privilege, any researcher or discipline. Arguments support a claim that Lonergan's perspective is well suited to guide nurse researchers participating on cross-disciplinary health research teams.

  18. Google Scholar, Scopus and the Web of Science: a longitudinal and cross-disciplinary comparison

    OpenAIRE

    Harzing, Anne-Wil; Alakangas, Satu

    2016-01-01

    This article aims to provide a systematic and comprehensive comparison of the coverage of the three major bibliometric databases: Google Scholar, Scopus and the Web of Science. Based on a sample of 146 senior academics in five broad disciplinary areas, we therefore provide both a longitudinal and a cross-disciplinary comparison of the three databases.\\ud \\ud Our longitudinal comparison of eight data points between 2013 and 2015 shows a consistent and reasonably stable quarterly growth for bot...

  19. Hypothesis-based weight of evidence: a tool for evaluating and communicating uncertainties and inconsistencies in the large body of evidence in proposing a carcinogenic mode of action--naphthalene as an example.

    Science.gov (United States)

    Rhomberg, Lorenz R; Bailey, Lisa A; Goodman, Julie E

    2010-09-01

    Human health risk assessment consists of bringing to bear a large body of in vitro, animal, and epidemiologic studies on the question of whether environmental exposures to a substance are a potential risk to humans. The body of scientific information is typically less than definitive and often contains apparent contradictions. Often various possible conclusions about potential human risks may be drawn from the data and these may vary from very strong to tenuous. The task, therefore, is to communicate the uncertainties in the inferences from the data effectively, giving proper consideration to contrary data and alternative scientifically plausible interpretations. We propose an approach, Hypothesis-Based Weight of Evidence (HBWoE), to organize, evaluate, and communicate the large body of available relevant data on a given chemical, using naphthalene as an example. The goal for our use of the term "weight of evidence" (WoE) is broad in that we express the relative degrees of credence that should be placed in alternative possible interpretations of the naphthalene data and hypothesized carcinogenic modes of action (MoAs), expressed in a way that shows how such credence is tied to specific scientific interpretations, considering consistencies, inconsistencies, and contradictions within the data set.

  20. Librarians as Part of Cross-Disciplinary, Multi-Institutional Team Projects: Experiences from the VIVO Collaboration.

    Science.gov (United States)

    Garcia-Milian, Rolando; Norton, Hannah F; Auten, Beth; Davis, Valrie I; Holmes, Kristi L; Johnson, Margeaux; Tennant, Michele R

    2013-01-01

    Cross-disciplinary, team-based collaboration is essential for addressing today's complex research questions, and librarians are increasingly entering into such collaborations. This study identifies skills needed as librarians integrate into cross-disciplinary teams, based on the experiences of librarians involved in the development and implementation of VIVO, a research discovery and collaboration platform. Participants discussed the challenges, skills gained, and lessons learned throughout the project. Their responses were analyzed in the light of the science of team science literature, and factors affecting collaboration on the VIVO team were identified. Skills in inclusive thinking, communication, perseverance, adaptability, and leadership were found to be essential.

  1. Librarians as Part of Cross-Disciplinary, Multi-Institutional Team Projects: Experiences from the VIVO Collaboration

    Science.gov (United States)

    Garcia-Milian, Rolando; Norton, Hannah F.; Auten, Beth; Davis, Valrie I.; Holmes, Kristi L.; Johnson, Margeaux; Tennant, Michele R.

    2013-01-01

    Cross-disciplinary, team-based collaboration is essential for addressing today’s complex research questions, and librarians are increasingly entering into such collaborations. This study identifies skills needed as librarians integrate into cross-disciplinary teams, based on the experiences of librarians involved in the development and implementation of VIVO, a research discovery and collaboration platform. Participants discussed the challenges, skills gained, and lessons learned throughout the project. Their responses were analyzed in the light of the science of team science literature, and factors affecting collaboration on the VIVO team were identified. Skills in inclusive thinking, communication, perseverance, adaptability, and leadership were found to be essential. PMID:23833333

  2. State-of-the-lagoon reports as vehicles of cross-disciplinary integration.

    Science.gov (United States)

    Zaucha, Jacek; Davoudi, Simin; Slob, Adriaan; Bouma, Geiske; van Meerkerk, Ingmar; Oen, Amy Mp; Breedveld, Gijs D

    2016-10-01

    An integrative approach across disciplines is needed for sustainable lagoon and estuary management as identified by integrated coastal zone management. The ARCH research project (Architecture and roadmap to manage multiple pressures on lagoons) has taken initial steps to overcome the boundaries between disciplines and focus on cross-disciplinary integration by addressing the driving forces, challenges, and problems at various case study sites. A model was developed as a boundary-spanning activity to produce joint knowledge and understanding. The backbone of the model is formed by the interaction between the natural and human systems, including economy and governance-based subsystems. The model was used to create state-of-the-lagoon reports for 10 case study sites (lagoons and estuarine coastal areas), with a geographical distribution covering all major seas surrounding Europe. The reports functioned as boundary objects to build joint knowledge. The experiences related to the framing of the model and its subsequent implementation at the case study sites have resulted in key recommendations on how to address the challenges of cross-disciplinary work required for the proper management of complex social-ecological systems such as lagoons, estuarine areas, and other land-sea regions. Cross-disciplinary integration is initially resource intensive and time consuming; one should set aside the required resources and invest efforts at the forefront. It is crucial to create engagement among the group of researchers by focusing on a joint, appealing overall concept that will stimulate cross-sectoral thinking and focusing on the identified problems as a link between collected evidence and future management needs. Different methods for collecting evidence should be applied including both quantitative (jointly agreed indicators) and qualitative (narratives) information. Cross-disciplinary integration is facilitated by functional boundary objects. Integration offers important

  3. Kyleo ® - mode of action under examination

    Directory of Open Access Journals (Sweden)

    Heibertshausen, Dagmar

    2014-02-01

    Full Text Available Kyleo® with two known active substances (ai is an innovative, modern herbicide for resistance management. Kyleo® contains 160 g/l 2,4-D and 240 g/l glyphosate. With an application rate of 5,0 l/ha, it shows a far better, faster effect on weeds such as field horsetail (Equisetum arvense, volunteer oilseed rape (Brassica napus and couch grass (Agropyron repens compared to a tank mix or the reference products (RP. This is explained by an unique new formulation technology that for the first time combines 2,4-D as acid and glyphosate as MIPA salt together with FHS. The new form of 2,4-D is lipophilic with better leaf absorption and greater photolytic degradation in the upper layers of soil. Tests with radioactive marked substances have verified the systemic properties of both ai compared to RP. The displacement of 2,4-D into the plant roots was demonstrated 48 h after application (hpt. 98% glyphosate absorption was observed in rape and couch grass – 10% (rape respectively 25% (couch grass greater than with RP. Higher absorption of the ai is characterised by a swifter effect, with stronger, visible symptoms after 24 h in rape and 96 h in couch grass. The rainfastness of Kyleo® was tested in greenhouse (GH trials with rape. Comparability of the test objects was simulated with a uniform glyphosate quantity of 360 g/ha and 10 l/m² simulated precipitation. 24% improved effect compared to RP was verified for 1 hpt rainfall, while 4% improved effect was recorded for rain simulation after 6 hpt. GH trials with wheat and a comparable glyphosate application quantity of 290 g/ha revealed differences of 23% and 22% compared to RP for rain simulation of 1 hpt and 6 hpt. Kyleo® stands out with a swift effect and better rainfastness. The results presented here prove a systemic mode of action, good rainfastness and swift effect of Kyleo.

  4. Adjuvanted vaccines: Aspects of immunosafety and modes of action

    NARCIS (Netherlands)

    van Aalst, S.

    2017-01-01

    New developments in vaccine design shift towards safe, though sometimes less immunogenic, subunit and synthetic antigens. Therefore, the majority of current vaccines require adjuvants to increase immunogenicity. Most adjuvants available were developed empirically and their mode of action is only

  5. Mode of action of Buddleja cordata verbascoside against Staphylococcus aureus.

    Science.gov (United States)

    Avila, J G; de Liverant, J G; Martínez, A; Martínez, G; Muñoz, J L; Arciniegas, A; Romo de Vivar, A

    1999-07-01

    We evaluate the mode of action of verbascoside obtained from Buddleja cordata against Staphylococcus aureus by killing kinetics and incorporation of precursors methods. Verbascoside induced lethal effect on S. aureus, by affecting protein synthesis and inhibiting leucine incorporation.

  6. The building of the EUDAT Cross-Disciplinary Data Infrastructure

    Science.gov (United States)

    Lecarpentier, Damien; Michelini, Alberto; Wittenburg, Peter

    2013-04-01

    The EUDAT project is a European data initiative that brings together a unique consortium of 25 partners - including research communities, national data and high performance computing (HPC) centers, technology providers, and funding agencies - from 13 countries. EUDAT aims to build a sustainable cross-disciplinary and cross-national Commom Data Infrastructure (CDI) that provides a set of shared services for accessing and preserving research data. The design and deployment of these services is being coordinated by multi-disciplinary task forces comprising representatives from research communities and data centers. One of EUDAT's fundamental goals is the facilitation of cross-disciplinary data-intensive science. By providing opportunity for disciplines from across the spectrum to share data and cross-fertilize ideas, the CDI will encourage progress towards this vision of open and participatory data-intensive science. EUDAT will also facilitate this process through the creation of teams of experts from different disciplines, aiming to cooperatively develop services to meet the needs of several communities. Five research communities joined the EUDAT initiative at the start - CLARIN (Linguistics), ENES (Climate Modeling), EPOS (Earth Sciences), LifeWatch (Environmental Sciences - Biodiversity), VPH (Biological and Medical Sciences). They are acting as partners in the project, and have clear tasks and commitments. Since EUDAT started on the 1st of October 2011, we have been reviewing the approaches and requirements of these five communities regarding the deployment and use of a cross-disciplinary and persistent data e-Infrastructure. This analysis was conducted through interviews and frequent interactions with representatives of the communities. In this talk will be provided an updated status of the current CDI with specific refernce to the solid Earth science commnity of EPOS.

  7. A Critical Review of Mode of Action (MOA) Assignment Classifications for Ecotoxicology

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human health toxicology. With increasing calls to assess thousands of chemicals, some of which have little available informatio...

  8. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: Evaluation of Available Methods

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human toxicology. With increasing calls to assess 1000s of chemicals, some of which have little available information other tha...

  9. Differences in Mode of Action of Cochinchinenin A and B on ...

    African Journals Online (AJOL)

    Based on pharmacological fundamental theory, the modes of action of cochinchinenin A and B on TTX-R channels were distinguished. Results: The scatter diagram which reflected the time variation of inhibition effect on TTX-R sodium currents induced by cochinchinenin A fitted well with occupancy theory equation ...

  10. Perspectives for elucidating the ethylenediurea (EDU) mode of action for protection against O3 phytotoxicity.

    Science.gov (United States)

    Agathokleous, Evgenios

    2017-08-01

    Ethylenediurea (EDU) has been widely studied for its effectiveness to protect plants against injuries caused by surface ozone (O3), however its mode of action remains unclear. So far, there is not a unified methodological approach and thus the methodology is quite arbitrary, thereby making it more difficult to generalize findings and understand the EDU mode of action. This review examines the question of whether potential N addition to plants by EDU is a fundamental underlying mechanism in protecting against O3 phytotoxicity. Yet, this review proposes an evidence-based hypothesis that EDU may protect plants against O3 deleterious effects upon generation of EDU-induced hormesis, i.e. by activating plant defense at low doses. This hypothesis challenges the future research directions. Revealing a hormesis-based EDU mode of action in protecting plants against O3 toxicity would have further implications to ecotoxicology and environmental safety. Furthermore, this review discusses the need for further studies on plant metabolism under EDU treatment through relevant experimental approach, and attempts to set the bases for approaching a unified methodology that will contribute in revealing the EDU mode of action. In this framework, focus is given to the main EDU application methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cross-disciplinary research in cancer: an opportunity to narrow the knowledge-practice gap.

    Science.gov (United States)

    Urquhart, R; Grunfeld, E; Jackson, L; Sargeant, J; Porter, G A

    2013-12-01

    Health services researchers have consistently identified a gap between what is identified as "best practice" and what actually happens in clinical care. Despite nearly two decades of a growing evidence-based practice movement, narrowing the knowledge-practice gap continues to be a slow, complex, and poorly understood process. Here, we contend that cross-disciplinary research is increasingly relevant and important to reducing that gap, particularly research that encompasses the notion of transdisciplinarity, wherein multiple academic disciplines and non-academic individuals and groups are integrated into the research process. The assimilation of diverse perspectives, research approaches, and types of knowledge is potentially effective in helping research teams tackle real-world patient care issues, create more practice-based evidence, and translate the results to clinical and community care settings. The goals of this paper are to present and discuss cross-disciplinary approaches to health research and to provide two examples of how engaging in such research may optimize the use of research in cancer care.

  12. Cross-disciplinary research in cancer: an opportunity to narrow the knowledge–practice gap

    Science.gov (United States)

    Urquhart, R.; Grunfeld, E.; Jackson, L.; Sargeant, J.; Porter, G.A.

    2013-01-01

    Health services researchers have consistently identified a gap between what is identified as “best practice” and what actually happens in clinical care. Despite nearly two decades of a growing evidence-based practice movement, narrowing the knowledge–practice gap continues to be a slow, complex, and poorly understood process. Here, we contend that cross-disciplinary research is increasingly relevant and important to reducing that gap, particularly research that encompasses the notion of transdisciplinarity, wherein multiple academic disciplines and non-academic individuals and groups are integrated into the research process. The assimilation of diverse perspectives, research approaches, and types of knowledge is potentially effective in helping research teams tackle real-world patient care issues, create more practice-based evidence, and translate the results to clinical and community care settings. The goals of this paper are to present and discuss cross-disciplinary approaches to health research and to provide two examples of how engaging in such research may optimize the use of research in cancer care. PMID:24311951

  13. Linking Data and Publications: Towards a Cross-Disciplinary Approach

    Directory of Open Access Journals (Sweden)

    Maarten Hoogerwerf

    2013-06-01

    Full Text Available In this paper, we tackle the challenge of linking scholarly information in multi-disciplinary research infrastructures. There is a trend towards linking publications with research data and other information, but, as it is still emerging, this is handled differently by various initiatives and disciplines. For OpenAIRE, a European cross-disciplinary publication infrastructure, this poses the challenge of supporting these heterogeneous practices. Hence, OpenAIRE wants to contribute to the development of a common approach for discipline-independent linking practices between publications, data, project information and researchers. To this end, we constructed two demonstrators to identify commonalities and differences. The results show the importance of stable and unique identifiers, and support a ‘by reference’ approach of interlinking research results. This approach allows discipline-specific research information to be managed independently in distributed systems and avoids redundant maintenance. Furthermore, it allows these disciplinary systems to manage the specialized structures of their contents themselves.

  14. Modes of Action of Microbially-Produced Phytotoxins

    Directory of Open Access Journals (Sweden)

    Franck E. Dayan

    2011-08-01

    Full Text Available Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin.

  15. Effect and mode of action of some systemic nematicides

    NARCIS (Netherlands)

    Bunt, J.A.

    1975-01-01

    In this study, nematicidal effects, mode of action and specific characters of some systemic nematicides were studied, in search of substitutes for the widely used soil fumigants that require high dosages. The thesis comprises:

    - a review of literature,
    - development of

  16. On the nature of cross-disciplinary integration: A philosophical framework.

    Science.gov (United States)

    O'Rourke, Michael; Crowley, Stephen; Gonnerman, Chad

    2016-04-01

    Meeting grand challenges requires responses that constructively combine multiple forms of expertise, both academic and non-academic; that is, it requires cross-disciplinary integration. But just what is cross-disciplinary integration? In this paper, we supply a preliminary answer by reviewing prominent accounts of cross-disciplinary integration from two literatures that are rarely brought together: cross-disciplinarity and philosophy of biology. Reflecting on similarities and differences in these accounts, we develop a framework that integrates their insights-integration as a generic combination process the details of which are determined by the specific contexts in which particular integrations occur. One such context is cross-disciplinary research, which yields cross-disciplinary integration. We close by reflecting on the potential applicability of this framework to research efforts aimed at meeting grand challenges. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Cross-disciplinary competency standards for work-related assessments: communicating the requirements for effective professional practice.

    Science.gov (United States)

    Travis, Jamie

    2002-01-01

    The purpose of this article is to introduce the cross-disciplinary competency standards for work-related assessments, why they are needed and how they have been developed in New South Wales (NSW). Cross-disciplinary competency standards communicate the benchmarks for effective performance of work-related assessments. They outline what is expected of rehabilitation professionals, including the ability to apply and transfer competence across different conditions and workplace contexts. Outcomes in occupational rehabilitation are affected by the efficacy of the work-related assessments performed, which is dependent upon competent, clinical decision-making by rehabilitation professionals. However, in Australia, work-related assessment practice is not governed by universally accepted competency standards or by any competency-based training/education and assessment system. To enhance professional practice, WorkCover NSW has developed cross-disciplinary competency standards for work-related a ssessments. The competencies provide (i) quality standards for professional workplace training and development, (ii) benchmarks for assessing the competence of rehabilitation professionals, (iii) a framework for evidence-based practice, (iv) benchmarks for measuring service quality and (v) "real world" learning outcomes and assessment criteria for professional education programs.

  18. Dendroecological opportunities to shift and cross disciplinary boundaries

    Science.gov (United States)

    Buentgen, Ulf

    2017-04-01

    In this 'solicited' talk, I will firstly navigate through some of the most influential dendroecological/-climatological advancements of roughly the last decade. Afterwards, I will outline pending challenges in modern tree-ring research, including the ongoing involvement of (quantitative) wood anatomical materials, methods and perspectives. Finally, I will provide several examples of how dendroecological approaches might indeed be able to contribute towards identifying and shifting research frontiers, as well as crossing disciplinary boundaries; not only within the vast field of natural sciences but also with the humanities. While presenting an array of timely case studies, with all of them being centered on either tree-ring data or associated techniques, this talk will comprise multiple aspects of archaeology, astronomy, biology, ecology, epidemiology, history, mycology and volcanology. In so doing, I hope to stimulate discussion on the potential and limitations of state-of-the-art tree-ring research across various spatiotemporal scales of resolution, which may range from the cell to the hemisphere and from the day to the Holocene. Despite its overview character, this talk will place emphases on utilizing big datasets, on valuing Russia's scientific landscape, on performing high-resolution radiocarbon measurements, and on linking volcanic activity, climate variability and human history.

  19. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action

    Science.gov (United States)

    Vincent, Isabel M.; Ehmann, David E.; Mills, Scott D.; Perros, Manos

    2016-01-01

    Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5′-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanide m-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl-transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5′-deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use. PMID:26833150

  20. Group Development and Integration in a Cross-Disciplinary and Intercultural Research Team

    Science.gov (United States)

    Kirk-Lawlor, Naomi; Allred, Shorna

    2017-04-01

    Cross-disciplinary research is necessary to solve many complex problems that affect society today, including problems involving linked social and environmental systems. Examples include natural resource management or scarcity problems, problematic effects of climate change, and environmental pollution issues. Intercultural research teams are needed to address many complex environmental matters as they often cross geographic and political boundaries, and involve people of different countries and cultures. It follows that disciplinarily and culturally diverse research teams have been organized to investigate and address environmental issues. This case study investigates a team composed of both monolingual and bilingual Chilean and US university researchers who are geoscientists, engineers and economists. The objective of this research team was to study both the natural and human parts of a hydrologic system in a hyper-arid region in northern Chile. Interviews ( n = 8) addressed research questions focusing on the interaction of cross-disciplinary diversity and cultural diversity during group integration and development within the team. The case study revealed that the group struggled more with cross-disciplinary challenges than with intercultural ones. Particularly challenging ones were instances the of disciplinary crosstalk, or hidden misunderstandings, where team members thought they understood their cross-disciplinary colleagues, when in reality they did not. Results showed that translation served as a facilitator to cross-disciplinary integration of the research team. The use of translation in group meetings as a strategy for effective cross-disciplinary integration can be extended to monolingual cross-disciplinary teams as well.

  1. RMS: a platform for managing cross-disciplinary and multi-institutional research project collaboration.

    Science.gov (United States)

    Luo, Jake; Apperson-Hansen, Carolyn; Pelfrey, Clara M; Zhang, Guo-Qiang

    2014-11-30

    Cross-institutional cross-disciplinary collaboration has become a trend as researchers move toward building more productive and innovative teams for scientific research. Research collaboration is significantly changing the organizational structure and strategies used in the clinical and translational science domain. However, due to the obstacles of diverse administrative structures, differences in area of expertise, and communication barriers, establishing and managing a cross-institutional research project is still a challenging task. We address these challenges by creating an integrated informatics platform to reduce the barriers to biomedical research collaboration. The Request Management System (RMS) is an informatics infrastructure designed to transform a patchwork of expertise and resources into an integrated support network. The RMS facilitates investigators' initiation of new collaborative projects and supports the management of the collaboration process. In RMS, experts and their knowledge areas are categorized and managed structurally to provide consistent service. A role-based collaborative workflow is tightly integrated with domain experts and services to streamline and monitor the life-cycle of a research project. The RMS has so far tracked over 1,500 investigators with over 4,800 tasks. The research network based on the data collected in RMS illustrated that the investigators' collaborative projects increased close to 3 times from 2009 to 2012. Our experience with RMS indicates that the platform reduces barriers for cross-institutional collaboration of biomedical research projects. Building a new generation of infrastructure to enhance cross-disciplinary and multi-institutional collaboration has become an important yet challenging task. In this paper, we share the experience of developing and utilizing a collaborative project management system. The results of this study demonstrate that a web-based integrated informatics platform can facilitate and

  2. Tweet My Street: A Cross-Disciplinary Collaboration for the Analysis of Local Twitter Data

    Directory of Open Access Journals (Sweden)

    Graeme Mearns

    2014-05-01

    Full Text Available Tweet My Street is a cross-disciplinary project exploring the extent to which data derived from Twitter can reveal more about spatial and temporal behaviours and the meanings attached to these locally. This is done with a longer-term view to supporting the coproduction and delivery of local services, complaint mechanisms and horizontal community support networks. The project has involved the development of a web-based software application capable of retrieving, storing and visualising geo-located “tweets” (and associated digital content from Twitter’s Firehose. This has been piloted in Newcastle upon Tyne (UK and has proven a scalable tool that can aid the analysis of social media data geographically. Beyond explaining efforts to analyse pilot data via this software, this paper elucidates three methodological challenges encountered during early collaboration. These include issues relating to “proximity” with subjects, ethics and critical questions about scholars’ digital responsibilities during the neogeographic turn.

  3. Mosquitocidal bacterial toxins: diversity, mode of action and resistance phenomena

    Directory of Open Access Journals (Sweden)

    Charles Jean-François

    2000-01-01

    Full Text Available Bacteria active against dipteran larvae (mosquitoes and black flies include a wide variety of Bacillus thuringiensis and B. sphaericus strains, as well as isolates of Brevibacillus laterosporus and Clostridium bifermentans. All display different spectra and levels of activity correlated with the nature of the toxins, mainly produced during the sporulation process. This paper describes the structure and mode of action of the main mosquitocidal toxins, in relationship with their potential use in mosquito and/or black fly larvae control. Investigations with laboratory and field colonies of mosquitoes that have become highly resistant to the B. sphaericus Bin toxin have shown that several mechanisms of resistance are involved, some affecting the toxin/receptor binding step, others unknown.

  4. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    Energy Technology Data Exchange (ETDEWEB)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

    2011-12-15

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  5. Exposure assessment of the cumulative intake of pesticides with dissimilar mode of action

    DEFF Research Database (Denmark)

    Jensen, Bodil Hamborg; Petersen, Annette; Christiansen, Sofie

    Risk assessment of pesticides is currently based on the no observed adverse effect levels (NOAELs) for effects of single compounds. However, humans might be exposed to a mixture of pesticides at the same time and the exposure could occur from more pesticides with endocrine disrupting effects....... In this study the effects of combined exposure from four endocrine disrupting pesticides have been investigated (procymidone, mancozeb, tebuconazole, and prochloraz). The four pesticides have dissimilar mode of actions. On the background of the potency for each pesticide to a given effect, a relative potency...... factor and the cumulative acute exposure of the pesticides have been estimated....

  6. Bebop on the Hockey Pitch: Cross-Disciplinary Creativity and Skills Transfer.

    Science.gov (United States)

    Harrison, Clive M

    2016-01-01

    This paper generalizes task-specific (but dissimilar) skills, from the jazz concert stage and from the hockey field, into the domain of creativity research. What is sought are clues to what skills or creativities are transferable across dissimilar domains. It is argued that certain domain-general skills are transferable across domains, but a domain-general or 'c' creative capacity, is not. Rather than transferring some over-arching capacity to be universally creative, this research highlights factors likely to facilitate successful cross-disciplinary creative expression and posits a correlation between the capacities for discriminant pattern-recognition, task-specific expertise, and sensory data-collection, and the transferability of creativity. Of particular significance is the capacity for informed, selective pattern-breaking based on the 'depth' or 'insider' perspective of the domain expert; such 'expert variation and selective retention' provides creative choices and responses that are likely to be perceived by the field as creative: valuable, novel and surprising. The author is a renowned Australian studio bassist, jazz musician, and music educator who also plays field hockey for Australia at Masters level. His recently completed Ph.D. thesis, based on a performance and composition career spanning 46 years, takes the form of an analytical autoethnography drawn from personal field notes, diaries and interviews as well as published record albums.

  7. Bebop on the Hockey pitch: Cross-disciplinary creativity and skills transfer

    Directory of Open Access Journals (Sweden)

    Clive Maxwell Harrison

    2016-02-01

    Full Text Available This paper generalises task-specific (but dissimilar skills, from the jazz concert stage and from the hockey field, into the domain of creativity research. What is sought are clues to what skills or creativities are transferable across dissimilar domains. It is argued that certain domain-general skills are transferable across domains, but a domain-general or ‘c’ creative capacity, is not. Rather than transferring some over-arching capacity to be universally creative, this research highlights factors likely to facilitate successful cross-disciplinary creative expression and posits a correlation between the capacities for discriminant pattern-recognition, task-specific expertise, and sensory data-collection, and the transferability of creativity. Of particular significance is the capacity for informed, selective pattern-breaking based on the ‘depth’ or ‘insider’ perspective of the domain expert; such ‘expert variation and selective retention’ (EVSR provides creative choices and responses that are likely to be perceived by the field as creative: valuable, novel and surprising. The author is a renowned Australian studio bassist, jazz musician, and music educator who also plays field hockey for Australia at Masters level. His recently completed PhD thesis, based on a performance and composition career spanning 46 years, takes the form of an analytical autoethnography drawn from personal field notes, diaries and interviews as well as published record albums.

  8. Understanding the cellular mode of action of vernakalant using a computational model: answers and new questions

    Directory of Open Access Journals (Sweden)

    Loewe Axel

    2015-09-01

    Full Text Available Vernakalant is a new antiarrhythmic agent for the treatment of atrial fibrillation. While it has proven to be effective in a large share of patients in clinical studies, its underlying mode of action is not fully understood. In this work, we aim to link experimental data from the subcellular, tissue, and system level using an in-silico approach. A Hill’s equation-based drug model was extended to cover the frequency dependence of sodium channel block. Two model variants were investigated: M1 based on subcellular data and M2 based on tissue level data. 6 action potential (AP markers were evaluated regarding their dose, frequency and substrate dependence. M1 comprising potassium, sodium, and calcium channel block reproduced the reported prolongation of the refractory period. M2 not including the effects on potassium channels reproduced reported AP morphology changes on the other hand. The experimentally observed increase of ERP accompanied by a shortening of APD90 was not reproduced. Thus, explanations for the drug-induced changes are provided while none of the models can explain the effects in their entirety. These results foster the understanding of vernakalant’s cellular mode of action and point out relevant gaps in our current knowledge to be addressed in future in-silico and experimental research on this aspiring antiarrhythmic agent.

  9. Rosmarinic acid: modes of action, medicinal values and health benefits.

    Science.gov (United States)

    Alagawany, Mahmoud; Abd El-Hack, Mohamed Ezzat; Farag, Mayada Ragab; Gopi, Marappan; Karthik, Kumaragurubaran; Malik, Yashpal Singh; Dhama, Kuldeep

    2017-11-07

    The supplementation of livestock rations with herbs containing bioactive components, such as rosmarinic acid (RA), have shown promising results as a natural feed additive in promoting growth, productive and reproductive performance, feed utilization, fertility, anti-oxidant status and immunologic indices. Furthermore, RA reportedly reduces the risks of various animal diseases and mitigates side effects of chemical and synthetic drugs. RA is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions. Additionally, RA is favored in meat industries due to enhancing the quality of meat products by reportedly improving shelf-life and imparting desirable flavor. This review describes the beneficial applications and recent findings with RA, including its natural sources, modes of action and various useful applications in safeguarding livestock health as well as important aspects of human health.

  10. Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2.

    Science.gov (United States)

    Hornyak, Peter; Askwith, Trevor; Walker, Sarah; Komulainen, Emilia; Paradowski, Michael; Pennicott, Lewis E; Bartlett, Edward J; Brissett, Nigel C; Raoof, Ali; Watson, Mandy; Jordan, Allan M; Ogilvie, Donald J; Ward, Simon E; Atack, John R; Pearl, Laurence H; Caldecott, Keith W; Oliver, Antony W

    2016-07-01

    Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a 5'-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II (TOP2). TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for high-throughput screen (HTS)-screening. We have gone on to determine crystal structures of these compounds bound to a 'humanized' form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2. © 2016 The Author(s).

  11. Insights from a cross-disciplinary seminar: 10 pivotal papers for ecological restoration

    Science.gov (United States)

    Melissa V. Eitzel; Sibyl Diver; Hillary Sardiñas; Lauren M. Hallett; Jessica J. Olson; Adam Romero; Gustavo de L. T. Oliveira; Alex T. Schuknecht; Rob Tidmore; Katharine N. Suding

    2011-01-01

    Restoration ecology is a deepening and diversifying field with current research incorporating multiple disciplines and infusing long-standing ideas with fresh perspectives. We present a list of 10 recent pivotal papers exemplifying new directions in ecological restoration that were selected by students in a cross-disciplinary graduate seminar at the University of...

  12. The Impact of Teacher Immediacy on Student Participation: An Objective Cross-Disciplinary Examination

    Science.gov (United States)

    Roberts, Amy; Friedman, Denise

    2013-01-01

    The current study examined how immediacy behaviors of college professors influence student participation. While these claims have been studied in the past, this investigation examined a cross-disciplinary sample and employed a more objective methodology, classroom observation. It was hypothesized that professors who showed greater immediacy would…

  13. Is there such a thing as online video game addiction? A cross-disciplinary review.

    NARCIS (Netherlands)

    Hellman, M.; Schoenmakers, T.M.; Nordstrom, B.R.; Holst, R.J. van

    2013-01-01

    Drawing on explanatory pluralism this cross-disciplinary theoretical study asks whether excessive compulsive online gaming can be called an addiction on the basis of what is known about the disorder. This article discusses the concept of addiction; the social seating of the problems and it reviews,

  14. [Cross-disciplinary support for a patient at the end of life].

    Science.gov (United States)

    Marchetti, Bruno; Araujo, Agnès; Mermet, Émilie

    2016-01-01

    A follow-up and rehabilitation care team implemented concerted, cross-disciplinary support with a patient nearing the end of her life. Working closely with the patient and her family, caregivers provided personalised palliative care. This account by members of the team shows the importance of the technical and relational dimensions in this context. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Cross-Disciplinary Thermoregulation and Sweat Analysis Laboratory Experiences for Undergraduate Chemistry and Exercise Science Students

    Science.gov (United States)

    Mulligan, Gregory; Taylor, Nichole; Glen, Mary; Tomlin, Dona; Gaul, Catherine A.

    2011-01-01

    Cross-disciplinary (CD) learning experiences benefit student understanding of concepts and curriculum by offering opportunities to explore topics from the perspectives of alternate fields of study. This report involves a qualitative evaluation of CD health sciences undergraduate laboratory experiences in which concepts and students from two…

  16. Is there such a thing as online video game addiction? A cross-disciplinary review

    NARCIS (Netherlands)

    Hellman, Matilda; Schoenmakers, Tim M.; Nordstrom, Benjamin R.; van Holst, Ruth J.

    2013-01-01

    Drawing on explanatory pluralism this cross-disciplinary theoretical study asks whether excessive compulsive online gaming can be called an addiction on the basis of what is known about the disorder. This article discusses the concept of addiction; the social seating of the problems and it reviews,

  17. A Framing Approach to Cross-disciplinary Research Collaboration: Experiences from a Large-scale Research Project on Adaptive Water Management

    Directory of Open Access Journals (Sweden)

    Art Dewulf

    2007-12-01

    Full Text Available Although cross-disciplinary research collaboration is necessary to achieve a better understanding of how human and natural systems are dynamically linked, it often turns out to be very difficult in practice. We outline a framing approach to cross-disciplinary research that focuses on the different perspectives that researchers from different backgrounds use to make sense of the issues they want to research jointly. Based on interviews, participants' evaluations, and our own observations during meetings, we analyze three aspects of frame diversity in a large-scale research project. First, we identify dimensions of difference in the way project members frame the central concept of adaptive water management. Second, we analyze the challenges provoked by the multiple framings of concepts. Third, we analyze how a number of interventions (interactive workshops, facilitation, group model building, and concrete case contexts contribute to the connection and integration of different frames through a process of joint learning and knowledge construction.

  18. Mode of action of cryoprotectants for sperm preservation.

    Science.gov (United States)

    Sieme, Harald; Oldenhof, Harriëtte; Wolkers, Willem F

    2016-06-01

    Sperm cryopreservation facilitates storage and transport for use in artificial reproduction technologies. Cryopreservation processing, however, exposes cells to stress resulting in cellular damage compromising sperm function. Cryoprotective agents are needed to minimize cryopreservation injury, but at higher concentration they are toxic to cells. In this review, we describe cryoinjury mechanisms, and modes of action of different types of cryoprotective agents. Furthermore, measures are discussed how to minimize toxic effects caused by adding and removing cryoprotective agents. Cryoprotective agents can be divided into permeating and non-permeating agents. Permeating agents such as glycerol can move across cellular membranes and modulate the rate and extent of cellular dehydration during freezing-induced membrane phase transitions. Permeating protectants provide intracellular protection because they are preferentially excluded from the surface of biomolecules thereby stabilizing the native state. Non-permeating agents can be divided into osmotically active smaller molecules and osmotically inactive macromolecules. Both, permeating and non-permeating protectants form a protective glassy state during freezing preserving biomolecular and cellular structures. Freezing extenders for sperm contain salts, buffer compounds, sugars, proteins and lipids, and typically contain glycerol as the main permeating cryoprotective agent providing intracellular protection. Non-permeating protectants including sugars and proteins are used as bulking agents and to increase the glass transition temperature of the freezing extender. Ultra-heat-treated milk and egg yolk are frequently added as membrane modifying agents to enhance the inherent sperm cryostability. The protocol how to use and add cryoprotectants is a compromise between their beneficial and potentially detrimental effects. Copyright © 2016. Published by Elsevier B.V.

  19. Life cycle responses of the midge Chironomus riparius to compounds with different modes of action

    NARCIS (Netherlands)

    Marinkovic, M.; Verweij, R.A.; Nummerdor, G.A.; Jonker, M.J.; Kraak, M.H.S.; Admiraal, W.

    2011-01-01

    Compounds with different modes of action may affect life cycles of biota differently. The aim of the present study was therefore to investigate the impact of four chemicals with different modes of action, including the essential metal copper, the nonessential metal cadmium, the organometal

  20. Life cycle responses of the midge Chironomus riparius to compounds with different modes of action.

    NARCIS (Netherlands)

    Marinkovic, M.; Verweij, R.A.; Nummerdor, G.A.; Jonker, M.J.; Kraak, M.H.S.; Admiraal, W.

    2011-01-01

    Compounds with different modes of action may affect life cycles of biota differently. The aim of the present study was therefore to investigate the impact of four chemicals with different modes of action, including the essential metal copper, the nonessential metal cadmium, the organometal

  1. Effects of insecticides with different modes of action in the control of ...

    African Journals Online (AJOL)

    The aim of the study was to evaluate the use of insecticides with different modes of action on banana borer weevil. Insecticides with different modes of action were administered to banana weevils (Cosmopolites sordidus) in small containers (1 litre by volume) with perforated lids and monitored in the laboratory at room ...

  2. Cross-Disciplinary Perspectives on Money Management by Addicts

    Science.gov (United States)

    Rosen, Marc I.

    2012-01-01

    How addicts manage their funds can be understood from studies of the neurobiology of impulsive spending, contingency management, self-reported expenditures, behavioral economics and anthropology. To show how these differing perspectives can provide theoretical explanations for observed behavior, they were applied to the question of when extra “windfall” funds are spent on substances of abuse. The treatment implications of Behavioral Economic and related approaches include targeting behavioral mechanisms of substance use with money management-based interventions, configuration of reinforcers other than substance use, and therapeutically framing the choice between abstinence and alcohol use. PMID:22211461

  3. Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

    Science.gov (United States)

    Pinson, Anneline; Franssen, Delphine; Gérard, Arlette; Parent, Anne-Simone; Bourguignon, Jean-Pierre

    Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the "altered function(s) of the endocrine system". Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  4. Integrating Sustainability into the Curriculum: Crossing Disciplinary Boundaries

    Science.gov (United States)

    Pushnik, J.

    2012-12-01

    The next generation will confront an increased number of global issues that interface the complexities of socioeconomic perspectives, environmental stability, poverty and development. Recently California State University Chico undertook a general education reform, providing a unique opportunity to craft a general education pathway to prepare students for these challenges by focusing a curriculum on sustainability. The Sustainability Pathway emphasizes a system thinking approach to help students understand and be able to address a set of problems involving the biosphere processes, human institutions and the economic vitality. The curriculum intentionally integrates courses from across the disciplines of natural sciences, social sciences, agriculture, engineering, economics, arts and humanities into a central focused theme of sustainability. The diverse backgrounds and academic focus of the participating faculty has necessitate the development of a common language and a cohesion within the curriculum. To address these needs a faculty learning community (FLC) was established to build on a common set of case studies. Three regional environmental water related issues were selected that had demonstrable socioeconomic, equity/ethical dimensions and environmental consequences. These case studies are Klamath River basin in northern California, the Bay-Delta project in the central part of the state and the Sultan Sea in southern California. Members of the FLC has contributed a perspective from their academic discipline which includes proposed reading lists, web based resources and PowerPoint presentations which are housed in common web- based resource repository. The pedagogical rational is to create linkages and cohesion among the courses in the curriculum by iteratively examining these case studies as basis for development of a multidisciplinary perspective as students progress through their general education.

  5. Specificity determinants for Cry insecticidal proteins: Insights from their mode of action.

    Science.gov (United States)

    Jurat-Fuentes, Juan Luis; Crickmore, Neil

    2017-01-01

    Insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) are used as active components of biopesticides and as plant incorporated protectants in transgenic crops. One of the most relevant attributes of these Bt protein-based insecticidal technologies is their high specificity, which assures lack of detrimental effects on non-target insects, vertebrates and the environment. The identification of specificity determinants in Bt insecticidal proteins could guide risk assessment for novel insecticidal proteins currently considered for commercialization. In this work we review the available data on specificity determinants of crystal (Cry) insecticidal proteins as the Bt toxins most well characterized and used in transgenic crops. The multi-step mode of action of the Cry insecticidal proteins allows various factors to potentially affect specificity determination and here we define seven levels that could influence specificity. The relative relevance of each of these determinants on efficacy of transgenic crops producing Cry insecticidal proteins is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Exploring Methodologies and Indicators for Cross-disciplinary Applications

    Science.gov (United States)

    Bernknopf, R.; Pearlman, J.

    2015-12-01

    Assessing the impact and benefit of geospatial information is a multidisciplinary task that involves the social, economic and environmental knowledge to formulate indicators and methods. There are use cases that couple the social sciences including economics, psychology, sociology that incorporate geospatial information. Benefit - cost analysis is an empirical approach that uses money as an indicator for decision making. It is a traditional base for a use case and has been applied to geospatial information and other areas. A new use case that applies indicators is Meta Regression analysis, which is used to evaluate transfers of socioeconomic benefits from different geographic regions into a unifying statistical approach. In this technique, qualitative and quantitative variables are indicators, which provide a weighted average of value for the nonmarket good or resource over a large region. The expected willingness to pay for the nonmarket good can be applied to a specific region. A third use case is the application of Decision Support Systems and Tools that have been used for forecasting agricultural prices and analysis of hazard policies. However, new methods for integrating these disciplines into use cases, an avenue to instruct the development of operational applications of geospatial information, are needed. Experience in one case may not be broadly transferable to other uses and applications if multiple disciplines are involved. To move forward, more use cases are needed and, especially, applications in the private sector. Applications are being examined across a multidisciplinary community for good examples that would be instructive in meeting the challenge. This presentation will look at the results of an investigation into directions in the broader applications of use cases to teach the methodologies and use of indicators that have applications across fields of interest.

  7. A cross-disciplinary understanding of incipient motion for effective environmental flow setting

    Science.gov (United States)

    Neverman, Andrew; Fuller, Ian; Death, Russell; Procter, Jon; Singh, Ranvir

    2016-04-01

    Environmental flow setting as a tool for maintaining ecological health in rivers has been a focus of debate for many years. Environmental flow setting often involves the establishment of base flow levels below impoundment structures as well as setting flushing flows in order to control excess periphyton accrual and sedimentation. The role of bedload transport and substrate stability is recognised as an integral part of effectively managing benthic communities, but environmental flow regulations often do not focus on managing sediment processes. Environmental flows which fail to scour periphyton have been attributed to increased biomass accumulation through increasing nutrient supply to periphyton mats. It may therefore be more effective to establish environmental flow models based on incipient motion thresholds. The aim of these models would be to establish target near-bed velocities as opposed to discharges. Establishment of such models requires an accurate understanding of the threshold conditions for incipient motion. Despite decades of incipient motion studies scientists are unable to consistently and accurately predict bedload transport in natural channels. Incipient motion results from a complex set of geomorphic, hydrologic, and ecological interactions operating over a range of spatial and temporal scales. Direct measurement of these processes can be difficult and time consuming, and has been restricted by a lack of suitable high spatio-temporal resolution methods in the past. This paper presents a cross-disciplinary approach to the study of incipient motion to develop effective environmental flow targets. Recent developments in remote sensing and 3D point cloud analysis are used to characterise substrate surfaces. Groundwater head pressures are measured during floods to examine changes in threshold velocities under different seepage conditions. The onset of bedload transport is recorded using impact plate sensors to relate transport initiation to near

  8. Stratum corneum hydration : mode of action of moisturizers on a molecular level

    NARCIS (Netherlands)

    Caussin, Julia

    2009-01-01

    In this thesis, the mode of action of stratum corneum moisturizers is studied using a variety of techniques: cryo-scanning electron microscopy, freeze fracture transmission electron microscopy, small angle X-ray diffraction and Fourier transform infrared spectroscopy.

  9. Mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna

    DEFF Research Database (Denmark)

    Syberg, K.; Engell-Kofoed, Anders Elleby; Pedersen, H.

    2008-01-01

    of similar- and dissimilar-acting toxicants equally well. CA and IA also equally predicted the ternary mixture consisting of both similar- and dissimilar-acting chemicals. The paper discusses the concept of mode of action and the implications the definition of mode of action has on the choice of reference......Mixture toxicity of similar- and dissimilar-acting toxicants can be predicted by the models concentration addition (CA) and independent action (IA) using single substance toxicity data. Knowledge of the toxicants mode of action is thus required in order to use the models. In order to test...... the predictive capability of the models, we conducted Daphnia magna 48 h immobilization experiments with three toxicants with known modes of action (dimethoate, pirimicarb and linear alkyl benzene sulfonate) singly, and in binary and ternary mixtures. Our results indicate that CA and IA predict binary mixtures...

  10. EarthServer: Cross-Disciplinary Earth Science Through Data Cube Analytics

    Science.gov (United States)

    Baumann, P.; Rossi, A. P.

    2016-12-01

    The unprecedented increase of imagery, in-situ measurements, and simulation data produced by Earth (and Planetary) Science observations missions bears a rich, yet not leveraged potential for getting insights from integrating such diverse datasets and transform scientific questions into actual queries to data, formulated in a standardized way.The intercontinental EarthServer [1] initiative is demonstrating new directions for flexible, scalable Earth Science services based on innovative NoSQL technology. Researchers from Europe, the US and Australia have teamed up to rigorously implement the concept of the datacube. Such a datacube may have spatial and temporal dimensions (such as a satellite image time series) and may unite an unlimited number of scenes. Independently from whatever efficient data structuring a server network may perform internally, users (scientist, planners, decision makers) will always see just a few datacubes they can slice and dice.EarthServer has established client [2] and server technology for such spatio-temporal datacubes. The underlying scalable array engine, rasdaman [3,4], enables direct interaction, including 3-D visualization, common EO data processing, and general analytics. Services exclusively rely on the open OGC "Big Geo Data" standards suite, the Web Coverage Service (WCS). Conversely, EarthServer has shaped and advanced WCS based on the experience gained. The first phase of EarthServer has advanced scalable array database technology into 150+ TB services. Currently, Petabyte datacubes are being built for ad-hoc and cross-disciplinary querying, e.g. using climate, Earth observation and ocean data.We will present the EarthServer approach, its impact on OGC / ISO / INSPIRE standardization, and its platform technology, rasdaman.References: [1] Baumann, et al. (2015) DOI: 10.1080/17538947.2014.1003106 [2] Hogan, P., (2011) NASA World Wind, Proceedings of the 2nd International Conference on Computing for Geospatial Research

  11. A cross-disciplinary approach to understanding neural stem cells in development and disease.

    Science.gov (United States)

    Henrique, Domingos; Bally-Cuif, Laure

    2010-06-01

    The Company of Biologists recently launched a new series of workshops aimed at bringing together scientists with different backgrounds to discuss cutting edge research in emerging and cross-disciplinary areas of biology. The first workshop was held at Wilton Park, Sussex, UK, and the chosen theme was 'Neural Stem Cells in Development and Disease', which is indeed a hot topic, not only because of the potential use of neural stem cells in cell replacement therapies to treat neurodegenerative diseases, but also because alterations in their behaviour can, in certain cases, lie at the origin of brain tumours and other diseases.

  12. Communication in ecosystem management: a case study of cross-disciplinary integration in the assessment phase of the interior Columbia Basin Ecosystem Management Project.

    Science.gov (United States)

    Jakobsen, Christine Haugaard; McLaughlin, William J

    2004-05-01

    Effective communication is essential to the success of collaborative ecosystem management projects. In this paper, we investigated the dynamics of the Interior Columbia Basin Ecosystem Management Project's (ICBEMP) cross-disciplinary integration process in the assessment phase. Using a case study research design, we captured the rich trail of experience through conducting in-depth interviews and collecting information from internal and public documents, videos, and meetings related to the ICBEMP. Coding and analysis was facilitated by a qualitative analysis software, NVivo. Results include the range of internal perspectives on barriers and facilitators of cross-disciplinary integration in the Science Integration Team (SIT). These are arrayed in terms of discipline-based differences, organizational structures and activities, individual traits of scientists, and previous working relationships. The ICBEMP organization included a team of communication staffs (CT), and the data described the CT as a mixed group in terms of qualifications and educational backgrounds that played a major role in communication with actors external to the ICBEMP organization but a minor one in terms of internal communication. The data indicated that the CT-SIT communication was influenced by characteristics of actors and structures related to organizations and their cultures. We conclude that the ICBEMP members may not have had a sufficient level of shared understanding of central domains, such as the task at hand and ways and timing of information sharing. The paper concludes by suggesting that future ecosystem management assessment teams use qualified communications specialists to design and monitor the development of shared cognition among organization members in order to improve the effectiveness of communication and cross-disciplinary integration.

  13. Roles of Natural Compounds from Medicinal Plants in Cancer Treatment: Structure and Mode of Action at Molecular Level.

    Science.gov (United States)

    Rasool, Mahmood; Malik, Arif; Manan, Abdul; Arooj, Mahwish; Qazi, Mahmood Husain; Kamal, Mohammad Amjad; Sheikh, Ishfaq Ahmed; Gan, Siew Hua; Asif, Muhammad; Naseer, Muhammad Imran

    2015-01-01

    Every year, cancer takes the life of millions of people. Conventional treatments have produced unsatisfactory results for some types of cancer, and the side effects are extensive, leading to a shift in the focus of treatment towards alternative medicines. Indeed, medicinal plants have long been investigated by scientists for their anti-cancer properties. Some phytochemicals that are important active constituents of plants, including catechins, ursolic acid, silymarin, glycyrrhizin, ellagic acid, gallic acid and various types of flavonoids, have shown promise in future cancer management. The current review covers various aspects of cancer treatment based on medicinal plants at molecular level and sheds light on their structures and modes of action.

  14. Spinal Cord Stimulation in Chronic Pain: Mode of Action.

    Science.gov (United States)

    Vallejo, Ricardo; Bradley, Kerry; Kapural, Leonardo

    2017-07-15

    Literature review. A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain. SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action. A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations. This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action. The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new

  15. Fluorides - mode of action and recommendations for use.

    Science.gov (United States)

    Lussi, Adrian; Hellwig, Elmar; Klimek, Joachim

    2012-01-01

    Various authors have shown that the caries decline in the industrialized countries during recent decades is based on the use of fluorides, of which local fluoride application in the form of fluoridated toothpastes is of primary importance. The caries-protective potential of fluorapatite is quite low; in contrast, dissolved fluorides in the vicinity of enamel are effective both in promoting remineralization and inhibiting demineralization. Considering the fact that the caries decline occurred at the same time that local fluoridation measures became widely used, the conclusion seems justified that regular application of F⁻ can inhibit caries.

  16. A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds

    Science.gov (United States)

    Gresham, David; Nishimura, Shinichi; Natarajan, Paramasivam; Koh, Judice L Y; Porter, Justin; Gray, Christopher A; Andersen, Raymond J; Giaever, Guri; Nislow, Corey; Andrews, Brenda; Botstein, David; Graham, Todd R; Yoshida, Minoru; Boone, Charles

    2013-01-01

    We present a yeast chemical-genomics approach designed to identify genes that when mutated confer drug resistance, thereby providing insight about the modes of action of compounds. We developed a molecular barcoded yeast open reading frame (MoBY-ORF) library in which each gene, controlled by its native promoter and terminator, is cloned into a centromere-based vector along with two unique oligonucleotide barcodes. The MoBY-ORF resource has numerous genetic and chemical-genetic applications, but here we focus on cloning wild-type versions of mutant drug-resistance genes using a complementation strategy and on simultaneously assaying the fitness of all transformants with barcode microarrays. The complementation cloning was validated by mutation detection using whole-genome yeast tiling microarrays, which identified unique polymorphisms associated with a drug-resistant mutant. We used the MoBY-ORF library to identify the genetic basis of several drug-resistant mutants and in this analysis discovered a new class of sterol-binding compounds. PMID:19349972

  17. Mode of action and human relevance of THF-induced mouse liver tumors.

    Science.gov (United States)

    Choi, Christopher J; Rushton, Erik K; Vardy, Audrey; Higgins, Larry; Augello, Andrea; Parod, Ralph J

    2017-07-05

    In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran (THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic activity was likely mediated via non-genotoxic modes of action (MOA). Based on evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out mice were orally exposed to THF to evaluate the potential role of CAR activation in the MOA for THF-induced liver tumors. Because data from this oral study with Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice (B6C3F1) reported by NTP and others were derived from different strains, oral studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF responses in both strains were comparable. As seen in inhalation studies with THF, oral exposure of wild type female mice to a maximum tolerated dose of THF increased total P450 content, CAR-related P450 activities, and hepatocyte proliferation; these effects were not observed in Car/Pxr knock-out female mice. This finding supports the hypothesis THF-induced carcinogenicity is likely mediated via CAR activation that has limited, if any, relevance to humans. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Predicting the aquatic toxicity mode of action using logistic regression and linear discriminant analysis.

    Science.gov (United States)

    Ren, Y Y; Zhou, L C; Yang, L; Liu, P Y; Zhao, B W; Liu, H X

    2016-09-01

    The paper highlights the use of the logistic regression (LR) method in the construction of acceptable statistically significant, robust and predictive models for the classification of chemicals according to their aquatic toxic modes of action. Essentials accounting for a reliable model were all considered carefully. The model predictors were selected by stepwise forward discriminant analysis (LDA) from a combined pool of experimental data and chemical structure-based descriptors calculated by the CODESSA and DRAGON software packages. Model predictive ability was validated both internally and externally. The applicability domain was checked by the leverage approach to verify prediction reliability. The obtained models are simple and easy to interpret. In general, LR performs much better than LDA and seems to be more attractive for the prediction of the more toxic compounds, i.e. compounds that exhibit excess toxicity versus non-polar narcotic compounds and more reactive compounds versus less reactive compounds. In addition, model fit and regression diagnostics was done through the influence plot which reflects the hat-values, studentized residuals, and Cook's distance statistics of each sample. Overdispersion was also checked for the LR model. The relationships between the descriptors and the aquatic toxic behaviour of compounds are also discussed.

  19. Specific immunotherapy-indications and mode of action.

    Science.gov (United States)

    Brehler, Randolf; Klimek, Ludger; Kopp, Matthias Volkmar; Christian Virchow, Johann

    2013-03-01

    It is estimated that up to 24% of the population in Germany suffers from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic rhinoconjunctivitis is closely related to other atopic diseases. This review is based on pertinent publications retrieved by a selective search of the Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses. Specific immunotherapy (SIT) is the only diseases-modifying treatment option for allergies. Meta-analysis reveals standardized mean differences in allergic rhinitis symptom scores of -0.73 for subcutaneous immunotherapy (SCIT) and -0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences in medication scores are -0.57 and -0.32, respectively. The treatment should be carried out for at least three years. It is indicated when the symptoms are severe and allergen avoidance is not a realistic option. The efficacy of treatment depends on the allergen dose; thus, every allergen preparation should be evaluated individually, independent of route of administration. SCIT can cause systemic adverse effects, including anaphylaxis. SLIT is safer but often causes allergic symptoms of the oral mucosa at the beginning of treatment. Even though the efficacy of SIT is well documented, it is still underused. SIT should be offered as standard treatment to patients suffering from allergic rhinitis.

  20. New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis.

    Science.gov (United States)

    Meek, M E; Boobis, A; Cote, I; Dellarco, V; Fotakis, G; Munn, S; Seed, J; Vickers, C

    2014-01-01

    The World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect the experience acquired in its application and extend its utility to emerging areas in toxicity testing and non-testing methods. The underlying principles have not changed, but the framework's scope has been extended to enable integration of information at different levels of biological organization and reflect evolving experience in a much broader range of potential applications. Mode of action/species concordance analysis can also inform hypothesis-based data generation and research priorities in support of risk assessment. The modified framework is incorporated within a roadmap, with feedback loops encouraging continuous refinement of fit-for-purpose testing strategies and risk assessment. Important in this construct is consideration of dose-response relationships and species concordance analysis in weight of evidence. The modified Bradford Hill considerations have been updated and additionally articulated to reflect increasing experience in application for cases where the toxicological outcome of chemical exposure is known. The modified framework can be used as originally intended, where the toxicological effects of chemical exposure are known, or in hypothesizing effects resulting from chemical exposure, using information on putative key events in established modes of action from appropriate in vitro or in silico systems and other lines of evidence. This modified mode of action framework and accompanying roadmap and case examples are expected to contribute to improving transparency in explicitly addressing weight of evidence considerations in mode of action/species concordance analysis based on both conventional data sources and evolving methods. Copyright © 2013 John Wiley & Sons, Ltd. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

  1. An entrancing tale of cross-disciplinary bridge building and burning in ethnopsychophysiomusicology

    Directory of Open Access Journals (Sweden)

    Petr Janata

    2009-06-01

    Full Text Available Having a paper accepted for publication is challenging, even under the best of circumstances, as when reporting an incremental finding in a field that is one’s home discipline. The process becomes considerably more difficult when venturing into foreign disciplines in which methodological conventions and assumptions may differ from those one is familiar with. Provocative topics may further exacerbate the reticence of reviewers and editors to welcome cross-disciplinary research to a journal’s pages. Here, a pair of papers, one of which describes a study of possible physiological correlates of music- induced trance states, and the other which describes the challenging journey to get the research performed and published, provide a case study for examining whether epistemological divides can be bridged in the face of editorial obstinacy.

  2. Differences in Mode of Action of Cochinchinenin A and B on ...

    African Journals Online (AJOL)

    HP

    of a drug could be determined by detecting time variation of drug effects. We suspect that the antagonistic interaction in the modulation on TTX-R sodium currents produced by the combination of cochinchinenin A and B may be related to their different modes of action on TTX-R sodium channels. Thus, the aim of this study ...

  3. Competitive exclusion as a mode of action of a novel Bacillus cereus aquaculture biological agent

    CSIR Research Space (South Africa)

    Lalloo, R

    2010-01-01

    Full Text Available B. cereus aquaculture biological agent by nutrient supplementation. Appl Microbiol 22 Biotechnol 83, 59–66. 23 Mode of action B. cereus 17 1 Meza, R.A., Monroy, A.F., Mercado, M., Poutou, R.A., Rodriguez, P. and Pedroza, A.P. (2004) 2 Study...

  4. Mode of action of pectin lyase A of Aspergillus niger on differently C6-substituted oligogalacturonides

    NARCIS (Netherlands)

    Alebeek, van G.J.W.M.; Christensen, T.M.I.E.; Schols, H.A.; Mikkelsen, J.D.; Voragen, A.G.J.

    2002-01-01

    A thorough investigation of the mode of action of Aspergillus niger (4M-147) pectin lyase A (PLA) on differently C6-substituted oligogalacturonides is described. PLA appeared to be very specific for fully methyl-esterified oligogalacturonides: removal of the methyl-ester or changing the type of

  5. Mode of action of the phenylpyrrole fungicide fenpiclonil in Fusarium sulphureum

    NARCIS (Netherlands)

    Jespers, A.B.K.

    1994-01-01

    In the last few decades, plant disease control has become heavily dependent on fungicides. Most modem fungicides were discovered by random synthesis and empirical optimization of lead structures. In general, these fungicides have specific modes of action and meet modem enviromnental

  6. Application of mass spectrometric techniques to delineate the modes-of-action of anticancer metallodrugs

    NARCIS (Netherlands)

    Hartinger, Christian G.; Groessl, Michael; Meier, Samuel M.; Casini, Angela; Dyson, Paul J.

    2013-01-01

    Mass spectrometry (MS) has emerged as an important tool for studying anticancer metallodrugs in complex biological samples and for characterising their interactions with biomolecules and potential targets on a molecular level. The exact modes-of-action of these coordination compounds and especially

  7. Mode of Action Profiles for Pesticide Compounds with Rodent Liver Tumor Outcomes

    Science.gov (United States)

    Mode of action (MOA) provides a central framework for assessing human relevance of adverse health outcomes observed in nonclinical safety studies. The goal of this study was to characterize MOA profiles for known rodent liver tumorigens identified from a database of pesticides as...

  8. FitSearch: a robust way to interpret a yeast fitness profile in terms of drug's mode-of-action.

    Science.gov (United States)

    Lee, Minho; Han, Sangjo; Chang, Hyeshik; Kwak, Youn-Sig; Weller, David M; Kim, Dongsup

    2013-01-01

    Yeast deletion-mutant collections have been successfully used to infer the mode-of-action of drugs especially by profiling chemical-genetic and genetic-genetic interactions on a genome-wide scale. Although tens of thousands of those profiles are publicly available, a lack of an accurate method for mining such data has been a major bottleneck for more widespread use of these useful resources. For general usage of those public resources, we designed FitRankDB as a general repository of fitness profiles, and developed a new search algorithm, FitSearch, for identifying the profiles that have a high similarity score with statistical significance for a given fitness profile. We demonstrated that our new repository and algorithm are highly beneficial to researchers who attempting to make hypotheses based on unknown modes-of-action of bioactive compounds, regardless of the types of experiments that have been performed using yeast deletion-mutant collection in various types of different measurement platforms, especially non-chip-based platforms. We showed that our new database and algorithm are useful when attempting to construct a hypothesis regarding the unknown function of a bioactive compound through small-scale experiments with a yeast deletion collection in a platform independent manner. The FitRankDB and FitSearch enhance the ease of searching public yeast fitness profiles and obtaining insights into unknown mechanisms of action of drugs. FitSearch is freely available at http://fitsearch.kaist.ac.kr.

  9. Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators.

    Science.gov (United States)

    Mihaich, Ellen M; Schäfers, Christoph; Dreier, David A; Hecker, Markus; Ortego, Lisa; Kawashima, Yukio; Dang, Zhi-Chao; Solomon, Keith

    2017-03-01

    As regulatory programs evaluate substances for their endocrine-disrupting properties, careful study design and data interpretation are needed to distinguish between responses that are truly endocrine specific and those that are not. This is particularly important in regulatory environments where criteria are under development to identify endocrine-disrupting properties to enable hazard-based regulation. Irrespective of these processes, most jurisdictions use the World Health Organization/International Programme on Chemical Safety definition of an endocrine disruptor, requiring that a substance is demonstrated to cause a change in endocrine function that consequently leads to an adverse effect in an intact organism. Such a definition is broad, and at its most cautious might capture many general mechanisms that would not specifically denote an endocrine disruptor. In addition, endocrine responses may be adaptive in nature, designed to maintain homeostasis rather than induce an irreversible adverse effect. The likelihood of indirect effects is increased in (eco)toxicological studies that require the use of maximum tolerated concentrations or doses, which must produce some adverse effect. The misidentification of indirect effects as truly endocrine mediated has serious consequences for prompting animal- and resource-intensive testing and regulatory consequences. To minimize the risk for misidentification, an objective and transparent weight-of-evidence procedure based on biological plausibility, essentiality, and empirical evidence of key events in an adverse outcome pathway is recommended to describe the modes of action that may be involved in toxic responses in nontarget organisms. Confounding factors such as systemic toxicity, general stress, and infection can add complexity to such an evaluation and should be considered in the weight of evidence. A recommended set of questions is proffered to help guide researchers and regulators in discerning endocrine and

  10. Machine learning algorithms for mode-of-action classification in toxicity assessment.

    Science.gov (United States)

    Zhang, Yile; Wong, Yau Shu; Deng, Jian; Anton, Cristina; Gabos, Stephan; Zhang, Weiping; Huang, Dorothy Yu; Jin, Can

    2016-01-01

    Real Time Cell Analysis (RTCA) technology is used to monitor cellular changes continuously over the entire exposure period. Combining with different testing concentrations, the profiles have potential in probing the mode of action (MOA) of the testing substances. In this paper, we present machine learning approaches for MOA assessment. Computational tools based on artificial neural network (ANN) and support vector machine (SVM) are developed to analyze the time-concentration response curves (TCRCs) of human cell lines responding to tested chemicals. The techniques are capable of learning data from given TCRCs with known MOA information and then making MOA classification for the unknown toxicity. A novel data processing step based on wavelet transform is introduced to extract important features from the original TCRC data. From the dose response curves, time interval leading to higher classification success rate can be selected as input to enhance the performance of the machine learning algorithm. This is particularly helpful when handling cases with limited and imbalanced data. The validation of the proposed method is demonstrated by the supervised learning algorithm applied to the exposure data of HepG2 cell line to 63 chemicals with 11 concentrations in each test case. Classification success rate in the range of 85 to 95 % are obtained using SVM for MOA classification with two clusters to cases up to four clusters. Wavelet transform is capable of capturing important features of TCRCs for MOA classification. The proposed SVM scheme incorporated with wavelet transform has a great potential for large scale MOA classification and high-through output chemical screening.

  11. Reassessment of MTBE cancer potency considering modes of action for MTBE and its metabolites.

    Science.gov (United States)

    Bogen, Kenneth T; Heilman, Jacqueline M

    2015-01-01

    A 1999 California state agency cancer potency (CP) evaluation of methyl tert-butyl ether (MTBE) assumed linear risk extrapolations from tumor data were plausible because of limited evidence that MTBE or its metabolites could damage DNA, and based such extrapolations on data from rat gavage and rat and mouse inhalation studies indicating elevated tumor rates in male rat kidney, male rat Leydig interstitial cells, and female rat leukemia/lymphomas. More recent data bearing on MTBE cancer potency include a rodent cancer bioassay of MTBE in drinking water; several new studies of MTBE genotoxicity; several similar evaluations of MTBE metabolites, formaldehyde, and tert-butyl alcohol or TBA; and updated evaluations of carcinogenic mode(s) of action (MOAs) of MTBE and MTBE metabolite's. The lymphoma/leukemia data used in the California assessment were recently declared unreliable by the U.S. Environmental Protection Agency (EPA). Updated characterizations of MTBE CP, and its uncertainty, are currently needed to address a variety of decision goals concerning historical and current MTBE contamination. To this end, an extensive review of data sets bearing on MTBE and metabolite genotoxicity, cytotoxicity, and tumorigenicity was applied to reassess MTBE CP and related uncertainty in view of MOA considerations. Adopting the traditional approach that cytotoxicity-driven cancer MOAs are inoperative at very low, non-cytotoxic dose levels, it was determined that MTBE most likely does not increase cancer risk unless chronic exposures induce target-tissue toxicity, including in sensitive individuals. However, the corresponding expected (or plausible upper bound) CP for MTBE conditional on a hypothetical linear (e.g., genotoxic) MOA was estimated to be ∼2 × 10(-5) (or 0.003) per mg MTBE per kg body weight per day for adults exposed chronically over a lifetime. Based on this conservative estimate of CP, if MTBE is carcinogenic to humans, it is among the weakest 10% of chemical

  12. Making It All Count: A Cross-Disciplinary Collaboration Model Incorporating Scholarship, Creative Activity, and Student Engagement

    Science.gov (United States)

    Dailey, Rocky; Hauschild-Mork, Melissa

    2017-01-01

    This study takes a grounded theory approach as a basis for a case study examining a cross-disciplinary artistic and academic collaborative project involving faculty from the areas of English, music, dance, theatre, design, and visual journalism resulting in the creation of research, scholarly, and creative activity that fosters student engagement…

  13. Broadening Student Learning Experiences via a Novel Cross-Disciplinary Art and Anatomy Education Program--A Case Study

    Science.gov (United States)

    Speed, Caroline J.; Kleiner, Adina; Macaulay, Janet O.

    2015-01-01

    This study explored student learning and engagement in a novel cross-disciplinary education program, in particular whether medical students learning experiences can be enhanced through interaction and exchange of knowledge with students of varying disciplines. The program, entitled AnaRtomy, studies the historical relationship between art and…

  14. A Cross-Disciplinary and Cross-Cultural Study of Directives in Discussions and Conclusions of Research Articles

    Science.gov (United States)

    Jalilifar, Alireza; Mehrabi, Khodayar

    2014-01-01

    The current study provided cross-cultural and cross-disciplinary analyses of the distribution of directives in discussion and conclusion sections of English and Persian research articles (RAs) in disciplines of physics, chemistry, counseling, and sociology, representing hard and soft sciences, respectively. To that aim, 80 RAs from both English…

  15. On the relevance of the NPY2-receptor variation for modes of action cascading processes.

    Science.gov (United States)

    Beste, Christian; Stock, Ann-Kathrin; Epplen, Jörg T; Arning, Larissa

    2014-11-15

    Every day, we encounter situations in which we have to deal with multiple response options. In order not to overstrain response selection resources, we need to cascade the associated task goals. Yet, the neurobiological foundations of these action cascading processes are largely unknown. Aiming at determining the possible relevance of the neuropeptide Y Y2 receptor for action cascading processes, this study investigates a functional promoter variation (rs2234759) in the neuropeptide Y Y2 receptor gene (NPY2R). 176 healthy subjects completed a stop-change paradigm. Applying mathematical constraints to the obtained behavioral data allowed for a classification of the action cascading processing mode on a serial to parallel continuum. Neurophysiological data (EEG) were analyzed along this mathematical constraint. The behavioral data show that the Y2-receptor high expression G allele is associated with a less efficient mode of action cascading where different task goals are activated in parallel. The neurophysiological data indicate that this effect is based on modulations at the response selection stage but not on changes in the preceding attentional selection processes. Analyses show that the interrelation between behavioral and neurophysiological data is mediated by genotype effects. At the level of response selection, genotype effects are associated with activity changes in the anterior cingulate cortex (ACC). Changes in the reliability of neural synchronization processes in the theta frequency band are also related to these effects. Possibly, these Y2-receptor-related effects emerge from the receptor's strong interrelation with the dopamine system. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Ochratoxin A in food and feed: occurrence, legislation and mode of action.

    Science.gov (United States)

    Höhler, D

    1998-03-01

    Ochratoxins, of which ochratoxin A (OA) is the most prevalent, are secondary fungal metabolites of some toxigenic species of Aspergillus and Penicillium. OA has been shown to be nephrotoxic, hepatotoxic, teratogenic, carcinogenic and immunosuppressive. The natural occurrence of OA in food and feed stuffs is widespread, especially in temperate areas such as Canada, Denmark, Germany, Sweden and the United Kingdom, and detectable amounts were even found in randomly collected human milk samples in Germany, Sweden and Italy. Of greatest concern in humans is its implicated role in an irreversible and fatal kidney disease referred to as Balkan Endemic Nephropathy. The mean dietary intake for humans in the European Union was found to be in the range of 1 to 2 ng/kg bw/day. Compared with the Provisional Tolerable Daily Intake (PTDI) proposed by the WHO of 16 ng OA/kg bw/day for humans, the average OA intake in Europe seems to be rather low. The main contributor to the OA intake in humans are cereals and cereal products, other possible contributors are coffee, beer, pork, products containing pig blood/plasma, pulses and spices. Only very few countries have regulations for OA in food and feed products. Based on the current literature, the mechanisms involved in the toxicity of OA indicate three major effects: (1) inhibition of mitochondrial respiration correlated with a depletion of ATP; (2) inhibition of tRNA-synthetase accompanied by a reduced protein synthesis; and (3) enhanced lipid peroxidation. Generation of free radicals and lipid peroxidation as an important mode of action of OA in vitro and in vivo is discussed in detail, as well as counteracting effects of dietary antioxidants.

  17. Odorant Receptor Modulation: Ternary Paradigm for Mode of Action of Insect Repellents

    Science.gov (United States)

    2012-01-01

    CqOR10-CqOrco exhibit sensitivity to these compounds in the high nanomolar range, which is matched by pheromone receptors of other insects in the same...transitions: a plausible model. J. Mol. Biol. 12, 88e118. Nakagawa, T., Sakurai, T., Nishioka, T., Touhara, K., 2005. Insect sex- pheromone signals mediated...Author’s personal copy Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents Jonathan D. Bohbot, Joseph C. Dickens

  18. Study of modes of action of the biocontrol agent metschnikowia and auensis pbc-2

    OpenAIRE

    Manso, Teresa; Vero, Silvana; González, M. Belén; Nunes, Carla

    2010-01-01

    Proceedings of the International Conference “Environmentally friendly and safe technologies for quality of fruit and vegetables”, held in Universidade do Algarve, Faro, Portugal, on January 14-16, 2009. This Conference was a join activity with COST Action 924. Metschnikowia andauensis NCYC 3728 (PBC-2) is an effective antagonist against the postharvest pathogens Penicillium expansum, Botrytis cinerea and Rhizopus stolofiner on pome fruits, however its mode of action is unknown....

  19. Antibacterial prenylated isoflavonoids and stilbenoids : quantitative structure-activity relationships and mode of action

    OpenAIRE

    Araya-Cloutier, Carla

    2017-01-01

    Prenylated phenolic compounds, i.e. those bearing a C5-isoprenoid  (prenyl) substituent, are abundant in plants from the Fabaceae (legume) family and are potential natural antibacterial agents against resistant pathogenic bacteria. To understand the antibacterial properties of these compounds, (quantitative) structure-activity relationships and mode of action of these molecules were investigated against Gram positive and negative bacteria. Compounds belonging to the flavonoid, isoflavono...

  20. Toxicity of 13 different antibiotics towards freshwater green algae Pseudokirchneriella subcapitata and their modes of action.

    Science.gov (United States)

    Fu, Ling; Huang, Tao; Wang, Shuo; Wang, Xiaohong; Su, Limin; Li, Chao; Zhao, Yuanhui

    2017-02-01

    Although modes of action (MOAs) play a key role in the understanding of the toxic mechanism of chemicals, the MOAs have not been investigated for antibiotics to green algae. This paper is to discriminate excess toxicity from baseline level and investigate the MOAs of 13 different antibiotics to algae by using the determined toxicity values. Comparison of the toxicities shows that the inhibitors of protein synthesis to bacteria, such as azithromycin, doxycycline, florfenicol and oxytetracycline, exhibit significantly toxic effects to algae. On the other hand, the cell wall synthesis inhibitors, such as cefotaxime and amoxicillin, show relatively low toxic effects to the algae. The concentrations determined by HPLC indicate that quinocetone and amoxicillin can be easily photodegraded or hydrolyzed during the toxic tests. The toxic effects of quinocetone and amoxicillin to the algae are attributed to not only their parent compounds, but also their metabolites. Investigation on the mode of action shows that, except rifampicin, all the tested antibiotics exhibit excess toxicity to Pseudokirchneriella subcapitata (P. subcapitata). These antibiotics can be identified as reactive modes of action to the algae. They act as electrophilic mechanism of action to P. subcapitata. These results are valuable for the understanding of the toxic mechanism to algae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Differing community responses to similar public health threats: a cross-disciplinary systematic literature review.

    Science.gov (United States)

    Greene, Giles; Turley, Ruth; Mann, Mala; Amlôt, Richard; Page, Lisa; Palmer, Stephen

    2014-02-01

    The way in which different communities respond to similar threats to their health can vary, from outrage to indifference and public health agencies are often taken by surprise leading to potential loss of public confidence. The objective of this systematic literature review was to seek to better understand the community-level drivers that might explain the variability in response. A vigorous systematic cross-disciplinary literature review was undertaken searching thirteen bibliographic databases and a variety of grey sources were screened. The social amplification of risk framework and the risk perception management theoretical models were used to assess evidence and data were synthesised by Narrative review. Sixteen studies meeting the agreed inclusion criteria described eleven different threats ranging from: infectious disease outbreaks to environmental disasters to cancer clusters, affecting two or more communities were identified from medical, psychological, social science and environmental science literature. There was wide heterogeneity between the type and quality of the studies. There was a general absence of theoretical underpinning community responses. Most studies did not report sufficient data to allow an appropriate amount of validity. Very low response rates in particular were common. Potential explanatory drivers suggested included, prior experience and visibility of threat, sociodemographic characteristics, volume and type of media coverage, government reaction and availability of social support. This review confirmed that there are significant differences. Further work is needed to develop theoretical models that apply to the community level and do not assume that a community's response is simply the aggregate of individual level responses. © 2013.

  2. Nurturing Opportunity Identification for Business Sophistication in a Cross-disciplinary Study Environment

    Directory of Open Access Journals (Sweden)

    Karine Oganisjana

    2012-12-01

    Full Text Available Opportunity identification is the key element of the entrepreneurial process; therefore the issue of developing this skill in students is a crucial task in contemporary European education which has recognized entrepreneurship as one of the lifelong learning key competences. The earlier opportunity identification becomes a habitual way of thinking and behavior across a broad range of contexts, the more likely that entrepreneurial disposition will steadily reside in students. In order to nurture opportunity identification in students for making them able to organize sophisticated businesses in the future, certain demands ought to be put forward as well to the teacher – the person who is to promote these qualities in their students. The paper reflects some findings of a research conducted within the frameworks of a workplace learning project for the teachers of one of Riga secondary schools (Latvia. The main goal of the project was to teach the teachers to identify hidden inner links between apparently unrelated things, phenomena and events within 10th grade study curriculum and connect them together and create new opportunities. The creation and solution of cross-disciplinary tasks were the means for achieving this goal.

  3. A cross disciplinary study of link decay and the effectiveness of mitigation techniques.

    Science.gov (United States)

    Hennessey, Jason; Ge, Steven

    2013-01-01

    The dynamic, decentralized world-wide-web has become an essential part of scientific research and communication. Researchers create thousands of web sites every year to share software, data and services. These valuable resources tend to disappear over time. The problem has been documented in many subject areas. Our goal is to conduct a cross-disciplinary investigation of the problem and test the effectiveness of existing remedies. We accessed 14,489 unique web pages found in the abstracts within Thomson Reuters' Web of Science citation index that were published between 1996 and 2010 and found that the median lifespan of these web pages was 9.3 years with 62% of them being archived. Survival analysis and logistic regression were used to find significant predictors of URL lifespan. The availability of a web page is most dependent on the time it is published and the top-level domain names. Similar statistical analysis revealed biases in current solutions: the Internet Archive favors web pages with fewer layers in the Universal Resource Locator (URL) while WebCite is significantly influenced by the source of publication. We also created a prototype for a process to submit web pages to the archives and increased coverage of our list of scientific webpages in the Internet Archive and WebCite by 22% and 255%, respectively. Our results show that link decay continues to be a problem across different disciplines and that current solutions for static web pages are helping and can be improved.

  4. Evaluation of acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum L.

    Science.gov (United States)

    da Silva, Iberê Ferreira; de Oliveira, Ruberlei Godinho; Mendes Soares, Ilsamar; da Costa Alvim, Tarso; Donizeti Ascêncio, Sérgio; de Oliveira Martins, Domingos Tabajara

    2014-01-01

    Piper umbellatum L., Piperaceae, is a shrub that grows up to 3m high. It is commonly known as "capeba" or "pariparoba" in Brazil. Tea prepared using the leaves of this plant is employed in the treatment of infections and inflammatory processes in different countries. Approximately 50 compounds, notably from the flavonoid, alkaloid, terpene, and sterol classes, have been isolated from the leaves of Piper umbellatum. To evaluate the acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum leaves (HEPu). Acute toxicity of HEPu against CHO-K1 cells was evaluated using a cytotoxicity assay with Alamar Blue and that against mice was assessed by the Hippocratic test. Antibacterial activity of HEPu was tested using the broth microdilution method using a panel of clinically relevant bacteria, and the effects of HEPu on the bacterial membrane were analyzed in detail. A preliminary phytochemical analysis based on coloration/precipitation was performed according to procedure described in the literature. Secondary metabolites detected were analyzed and confirmed by thin layer chromatography (TLC), spectrophotometry, and high performance liquid chromatography (HPLC). Piper umbellatum did not appear to be toxic in the in vitro (IC50>200 µg/mL) cytotoxicity test. When administered in vivo at doses up to 2000 mg/kg p.o., HEPu did not cause any signs or symptoms of toxicity in mice. It demonstrated a good spectrum of antibacterial activity and its mode of action appeared to be associated with changes in the permeability of bacterial membranes; it led to increased entry of hydrophobic antibiotics, efflux of K(+), and nucleotide leakage. Preliminary phytochemical analysis revealed the presence of flavonoids, alkaloids, terpenes, and sterols in the extract. Spectrophotometric and HPLC analysis revealed the presence of the flavonoids rutin and quercetin. In summary, HEPu has antibacterial activity and low acute toxicity in vitro and

  5. Essential oils in food preservation: mode of action, synergies, and interactions with food matrix components

    Directory of Open Access Journals (Sweden)

    Morten eHyldgaard

    2012-01-01

    Full Text Available Essential oils are aromatic and volatile liquids extracted from plants. The chemicals in essential oils are secondary metabolites, which play an important role in plant defence as they often possess antimicrobial properties. The interest in essential oils and their application in food preservation has been amplified in recent years by an increasingly negative consumer perception of synthetic preservatives. Furthermore, food-borne diseases are a growing public health problem worldwide, calling for more effective preservation strategies. The antibacterial properties of essential oils and their constituents have been documented extensively. Pioneering work has also elucidated the mode of action of a few essential oil constituents, but detailed knowledge about most of the compounds' mode of action is still lacking. This knowledge is particularly important to predict their effect on different microorganisms, how they interact with food matrix components, and how they work in combination with other antimicrobial compounds. The main obstacle for using essential oil constituents as food preservatives is that they are most often not potent enough as single components, and they cause negative organoleptic effects when added in sufficient amounts to provide an antimicrobial effect. Exploiting synergies between several compounds has been suggested as a solution to this problem. However, little is known about which interactions lead to synergistic, additive, or antagonistic effects. Such knowledge could contribute to design of new and more potent antimicrobial blends, and to understand the interplay between the constituents of crude essential oils. The purpose of this review is to provide an overview of current knowledge about the antibacterial properties and antibacterial mode of action of essential oils and their constituents, and to identify research avenues that can facilitate implementation of essential oils as natural preservatives in foods.

  6. Essential Oils in Food Preservation: Mode of Action, Synergies, and Interactions with Food Matrix Components

    Science.gov (United States)

    Hyldgaard, Morten; Mygind, Tina; Meyer, Rikke Louise

    2012-01-01

    Essential oils are aromatic and volatile liquids extracted from plants. The chemicals in essential oils are secondary metabolites, which play an important role in plant defense as they often possess antimicrobial properties. The interest in essential oils and their application in food preservation has been amplified in recent years by an increasingly negative consumer perception of synthetic preservatives. Furthermore, food-borne diseases are a growing public health problem worldwide, calling for more effective preservation strategies. The antibacterial properties of essential oils and their constituents have been documented extensively. Pioneering work has also elucidated the mode of action of a few essential oil constituents, but detailed knowledge about most of the compounds’ mode of action is still lacking. This knowledge is particularly important to predict their effect on different microorganisms, how they interact with food matrix components, and how they work in combination with other antimicrobial compounds. The main obstacle for using essential oil constituents as food preservatives is that they are most often not potent enough as single components, and they cause negative organoleptic effects when added in sufficient amounts to provide an antimicrobial effect. Exploiting synergies between several compounds has been suggested as a solution to this problem. However, little is known about which interactions lead to synergistic, additive, or antagonistic effects. Such knowledge could contribute to design of new and more potent antimicrobial blends, and to understand the interplay between the constituents of crude essential oils. The purpose of this review is to provide an overview of current knowledge about the antibacterial properties and antibacterial mode of action of essential oils and their constituents, and to identify research avenues that can facilitate implementation of essential oils as natural preservatives in foods. PMID:22291693

  7. Mechanistic understanding of the modes of action of foam control agents.

    Science.gov (United States)

    Denkov, Nikolai D; Marinova, Krastanka G; Tcholakova, Slavka S

    2014-04-01

    In this paper we present briefly our current understanding of the modes of action of foam control agents (often termed "defoamers" or "antifoams"). After summarizing the background knowledge, reviewed in previous articles, the focus of the presentation is shifted to the antifoam studies from the last decade. The new experimental results, obtained by various research groups, are reviewed briefly to reveal the main mechanisms of antifoam action and the related key factors, governing the efficiency of the foam control agents. The role of the entry, spreading and bridging coefficients, of the entry barrier of the antifoam entities, and of the dynamics of surfactant adsorption is specifically discussed. © 2013.

  8. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review

    DEFF Research Database (Denmark)

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad

    2016-01-01

    benefits to the host fish and the rearing environment. The staggering number of probiotics papers in aquaculture highlights the multitude of advantages from these microorganisms and conspicuously position them in the dynamic search for health-promoting alternatives for cultured fish. This paper provides...... in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment...

  9. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review.

    Science.gov (United States)

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad; Tiwari, Ruchi; Karthik, K; Dhama, Kuldeep; Lazado, Carlo C

    2016-12-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment. Several probiotics have been characterized and applied in fish and a number of them are of host origin. Unlike some disease control alternatives being adapted and proposed in aquaculture where actions are unilateral, the immense potential of probiotics lies on their multiple mechanisms in conferring benefits to the host fish and the rearing environment. The staggering number of probiotics papers in aquaculture highlights the multitude of advantages from these microorganisms and conspicuously position them in the dynamic search for health-promoting alternatives for cultured fish. This paper provides an update on the use of probiotics in finfish aquaculture, particularly focusing on their modes of action. It explores the contemporary understanding of their spatial and nutritional competitiveness, inhibitory metabolites, environmental modification capability, immunomodulatory potential and stress-alleviating mechanism. This timely update affirms the importance of probiotics in fostering sustainable approaches in aquaculture and provides avenues in furthering its research and development.

  10. Stress Responses as a Tool To Detect and Characterize the Mode of Action of Antibacterial Agents

    Science.gov (United States)

    Bianchi, Allison A.; Baneyx, François

    1999-01-01

    Single-copy gene fusions between the lacZ reporter gene and Escherichia coli strains containing promoters induced by cold shock (cspA), cytoplasmic stress (ibp), or protein misfolding in the cell envelope (P3rpoH) were constructed and tested to determine their ability to detect antibacterial agents while simultaneously providing information on their cellular targets. Antibiotics that affect prokaryotic ribosomes selectively induced the cspA::lacZ or ibp::lacZ gene fusion, depending on their mode of action. The membrane-damaging peptide polymyxin B induced both the P3rpoH::lacZ and ibp::lacZ fusions, while the β-lactam antibacterial agent carbenicillin activated only the P3rpoH promoter. Nalidixic acid, a compound that causes DNA damage, downregulated β-galactosidase synthesis from P3rpoH but had little effect on expression of the reporter enzyme from either the cspA or ibp promoter. All model antibiotics could be identified over a wide range of sublethal concentrations with signal-to-noise ratios between 2 and 11. A blue halo assay was developed to rapidly characterize the modes of action of antibacterial agents by visual inspection, and this assay was used to detect chloramphenicol secreted into the growth medium of Streptomyces venezuelae cultures. This simple system holds promise for screening natural or combinatorial libraries of antimicrobial compounds. PMID:10543818

  11. Mode of Action of Lactoperoxidase as Related to Its Antimicrobial Activity: A Review

    Directory of Open Access Journals (Sweden)

    F. Bafort

    2014-01-01

    Full Text Available Lactoperoxidase is a member of the family of the mammalian heme peroxidases which have a broad spectrum of activity. Their best known effect is their antimicrobial activity that arouses much interest in in vivo and in vitro applications. In this context, the proper use of lactoperoxidase needs a good understanding of its mode of action, of the factors that favor or limit its activity, and of the features and properties of the active molecules. The first part of this review describes briefly the classification of mammalian peroxidases and their role in the human immune system and in host cell damage. The second part summarizes present knowledge on the mode of action of lactoperoxidase, with special focus on the characteristics to be taken into account for in vitro or in vivo antimicrobial use. The last part looks upon the characteristics of the active molecule produced by lactoperoxidase in the presence of thiocyanate and/or iodide with implication(s on its antimicrobial activity.

  12. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  13. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.

    Science.gov (United States)

    Rajashekar, Yallappa; Shivanandappa, Thimmappa

    2017-01-01

    Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s) for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood.

  14. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.

    Directory of Open Access Journals (Sweden)

    Yallappa Rajashekar

    Full Text Available Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood.

  15. SEARCH: Study of Environmental Arctic Change--A System-scale, Cross-disciplinary Arctic Research Program

    Science.gov (United States)

    Shnoro, R. S.; Eicken, H.; Francis, J. A.; Scambos, T. A.; Schuur, E. A.; Straneo, F.; Wiggins, H. V.

    2013-12-01

    SEARCH is an interdisciplinary, interagency program that works with academic and government agency scientists and stakeholders to plan, conduct, and synthesize studies of Arctic change. Over the past three years, SEARCH has developed a new vision and mission, a set of prioritized cross-disciplinary 5-year goals, an integrated set of activities, and an organizational structure. The vision of SEARCH is to provide scientific understanding of arctic environmental change to help society understand and respond to a rapidly changing Arctic. SEARCH's 5-year science goals include: 1. Improve understanding, advance prediction, and explore consequences of changing Arctic sea ice. 2. Document and understand how degradation of near-surface permafrost will affect Arctic and global systems. 3. Improve predictions of future land-ice loss and impacts on sea level. 4. Analyze societal and policy implications of Arctic environmental change. Action Teams organized around each of the 5-year goals will serve as standing groups responsible for implementing specific goal activities. Members will be drawn from academia, different agencies and stakeholders, with a range of disciplinary backgrounds and perspectives. 'Arctic Futures 2050' scenarios tasks will describe plausible future states of the arctic system based on recent trajectories and projected changes. These scenarios will combine a range of data including climate model output, paleo-data, results from data synthesis and systems modeling, as well as expert scientific and traditional knowledge. Current activities include: - Arctic Observing Network (AON) - coordinating a system of atmospheric, land- and ocean-based environmental monitoring capabilities that will significantly advance our observations of arctic environmental conditions. - Arctic Sea Ice Outlook - an international effort that provides monthly summer reports synthesizing community estimates of the expected sea ice minimum. A newly-launched Sea Ice Prediction Network

  16. The Data Conservancy Service: An adaptable and evolvable data curation infrastructure supporting cross-disciplinary science

    Science.gov (United States)

    Choudhury, G. S.

    2011-12-01

    The Data Conservancy (DC) is one of the first of two programs established under National Science Foundation's DataNet initiative, whose goal it is to establish a national-scale infrastructure for science data preservation, sharing and re-use. Now entering its third year the DC has successfully developed an initial architecture and software called the Data Conservancy Service (DCS) anticipating the launch of production service in the summer of 2012. The DCS implements a Service-Oriented Architecture (SOA) that is designed to evolve into a federated infrastructure for long term storage, discovery and access to science data from a wide range of disciplines. Although the Data Conservancy must accommodate a great heterogeneity in the data models from these disciplines, the DCS itself does not define a canonical or normalized model to represent the science data it manages. Instead, the DCS data models are not science data models themselves but enable the extraction, querying and analysis of information units within the data it manages while also supporting the processes of a long-term, trusted digital archive including preservation. Through a customizable indexing service the DCS can utilize the discipline models developed by scientists for analysis and further processing. This approach enables innovation and allows the DC to ensure that the data it manages remains intact, accessible and usable while recognizing that every aspect of science and technology will change over time. The value of the DCS approach to supporting cross-disciplinary science has been demonstrated already through a pilot project in which the DCS curated a highly diverse collection of data gathered over years of field research in the Dry Valleys of Antarctica. During the curation process at Johns Hopkins University it was realized photographs documenting Dry Valleys collection sites documented the conditions of glaciers in the valleys, which have been changing rapidly over recent decades. Now, the

  17. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

    2007-01-01

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

  18. Gallesia integrifolia (Spreng.) Harms: In vitro and in vivo antibacterial activities and mode of action.

    Science.gov (United States)

    Arunachalam, Karuppusamy; Ascêncio, Sérgio Donizeti; Soares, Ilsamar Mendes; Souza Aguiar, Raimundo Wagner; da Silva, Larissa Irene; de Oliveira, Ruberlei Godinho; Balogun, Sikiru Olaitan; de Oliveira Martins, Domingos Tabajara

    2016-05-26

    Gallesia integrifolia (Phytolaccaceae) is commonly known as "pau-d'alho" in Brazil or "garlic plant" due to the strong scent of garlic peculiar to all parts of the plant. The bark decoction is used for the treatment of microbial infections among other diseases by different ethnic groups in Brazil, Peruvian Amazonians, Bolivia and Mosetene Indians. This study aimed to advance in the antibacterial activity and characterize the mode of action of the hydroethanolic extract of the inner stem bark of G. integrifolia (HEGi) using in vivo and in vitro experimental models. The qualitative and quantitative phytochemical analyzes of HEGi were carried out using colorimetric and HPLC technique. The cytotoxic potential of HEGi was evaluated against CHO-K1 cells by Alamar blue assay and its acute toxicity was assessed by the Hippocratic screening test using Swiss-Webster mice. The antibacterial activity was evaluated by micro- dilution method against ten strains of Gram-positive and Gram-negative bacteria. The mode of action of HEGi was investigated by outer membrane permeability, nucleotide leakage and potassium efflux assays. In vivo infection model was established by using Staphylococcus aureus infection model Wistar rats. Qualitative phytochemical analysis of HEGi revealed the presence of saponins, alkaloids, phenolic compounds and flavonoids. Phytochemical quantification of HEGi showed that higher total phenolic (80.10±0.62mg GAE/g) and flavonoid (16.10±0.03mg RE/g) contents. HPLC fingerprint analysis revealed the presence of gallic acid, rutin, and morin. In the Alamar blue assay no cytotoxic effect of HEGi in CHO-K1 cells was observed up to 200µg/mL, and no signs or symptoms of acute toxicity were observed in mice of both sexes at higher doses of up to 2000mg/kg, p.o. HEGi demonstrated bacteriostatic effect against selected Gram positive and Gram negative bacterial pathogens. Its mode of action is associated, at least partly, with changes in the permeability of

  19. Reconsidering the nature and mode of action of metabolite retrograde signals from the chloroplast

    Directory of Open Access Journals (Sweden)

    Gonzalo Martín Estavillo

    2013-01-01

    Full Text Available Plant organelles produce retrograde signals to alter nuclear gene expression in order to coordinate their biogenesis, maintain homeostasis or optimize their performance under adverse conditions. Many signals of different chemical nature have been described in the past decades, including chlorophyll intermediates, reactive oxygen species and adenosine derivatives. While the effects of retrograde signalling on gene expression are well understood, the initiation and transport of the signals and their mode of action have either not been resolved, or are a matter of speculation. Moreover, retrograde signalling should be consider as part of a broader cellular network, instead of as separate pathways, required to adjust to changing physiologically relevant conditions. Here we summarize current plastid retrograde signalling models in plants, with a focus on new signalling pathways, SAL1-PAP, MEcPP and β- cyclocitral, and outline missing links or future areas of research that we believe need to be addressed to have a better understanding of plant intracellular signalling networks.

  20. Nanovesicle encapsulation of antimicrobial peptide P34: physicochemical characterization and mode of action on Listeria monocytogenes

    Science.gov (United States)

    da Silva Malheiros, Patrícia; Sant'Anna, Voltaire; Micheletto, Yasmine Miguel Serafini; da Silveira, Nadya Pesce; Brandelli, Adriano

    2011-08-01

    Antimicrobial peptide P34, a substance showing antibacterial activity against pathogenic and food spoilage bacteria, was encapsulated in liposomes prepared from partially purified soybean phosphatidylcholine, and their physicochemical characteristics were evaluated. The antimicrobial activity was estimated by agar diffusion assay using Listeria monocytogenes ATCC 7644 as indicator strain. A concentration of 3,200 AU/mL of P34 was encapsulated in nanovesicles and stocked at 4 °C. No significant difference ( p > 0.05) in the biological activity of free and encapsulated P34 was observed through 24 days. Size and PDI of liposomes, investigated by light scattering analysis, were on average 150 nm and 0.22 respectively. Zeta potential was -27.42 mV. There was no significant change ( p > 0.05) in the physicochemical properties of liposomes during the time of evaluation. The liposomes presented closed spherical morphology as visualized by transmission electron microscopy (TEM). The mode of action of liposome-encapsulated P34 under L. monocytogenes cells was investigated by TEM. Liposomes appeared to adhere but not fuse with the bacterial cell wall, suggesting that the antimicrobial is released from nanovesicles to act against the microorganism. The effect of free and encapsulated P34 was tested against L. monocytogenes, showing that free bacteriocin inhibited the pathogen more quickly than the encapsulated P34. Liposomes prepared with low-cost lipid showed high encapsulation efficiency for a new antimicrobial peptide and were stable during storage. The mode of action against the pathogen L. monocytogenes was characterized.

  1. Antibiotic resistance modulation and modes of action of (--α-pinene in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Jasna Kovač

    Full Text Available The aim of the study was to investigate the mode of action of (--α-pinene in terms of its modulation of antibiotic resistance in Campylobacter jejuni. Broth microdilution and ethidium bromide accumulation assays were used to evaluate the (--α-pinene antimicrobial activity, modulation of antimicrobial resistance, and inhibition of antimicrobial efflux. The target antimicrobial efflux systems were identified using an insertion mutagenesis approach, and C. jejuni adaptation to (--α-pinene was evaluated using DNA microarrays. Knock-out mutants of the key up-regulated transcriptional regulators hspR and hrcA were constructed to investigate their roles in C. jejuni adaptation to several stress factors, including osmolytes, and pH, using Biolog phenotypical microarrays. Our data demonstrate that (--α-pinene efficiently modulates antibiotic resistance in C. jejuni by decreasing the minimum inhibitory concentrations of ciprofloxacin, erythromycin and triclosan by up to 512-fold. Furthermore, (--α-pinene promotes increased expression of cmeABC and another putative antimicrobial efflux gene, Cj1687. The ethidium bromide accumulation was greater in the wild-type strain than in the antimicrobial efflux mutant strains, which indicates that these antimicrobial efflux systems are a target of action of (--α-pinene. Additionally, (--α-pinene decreases membrane integrity, which suggests that enhanced microbial influx is a secondary mode of action of (--α-pinene. Transcriptomic analysis indicated that (--α-pinene disrupts multiple metabolic pathways, and particularly those involved in heat-shock responses. Thus, (--α-pinene has significant activity in the modulation of antibiotic resistance in C. jejuni, which appears to be mediated by multiple mechanisms that include inhibition of microbial efflux, decreased membrane integrity, and metabolic disruption. These data warrant further studies on (--α-pinene to develop its use in the control of antibiotic

  2. The synergy and mode of action of quercetin plus amoxicillin against amoxicillin-resistant Staphylococcus epidermidis.

    Science.gov (United States)

    Siriwong, Supatcharee; Teethaisong, Yothin; Thumanu, Kanjana; Dunkhunthod, Benjawan; Eumkeb, Griangsak

    2016-08-04

    Staphylococcus epidermidis is one of the most multiple resistances to antibiotics in the recent years. Therefore, practically-prescribed antibiotics in the treatment of these strains are not effective. Plant-derived antibacterial is one of the most interesting sources of new therapeutics. The present study was to investigate antibacterial, synergy and modes of action of quercetin and amoxicillin against amoxicillin-resistant Staphylococcus epidermidis (ARSE). The MICs, checkerboard assay, viability curves, cytoplasmic membrane (CM) permeability, enzyme assay, transmission electron microscopy, confocal microscopy and FT-IR microspectroscopy measurement was performed. The MICs of amoxicillin, penicillin, quercetin and kaempferol against all ARSE strains were 16, 200, 256-384 and >1024 μg/mL respectively. Synergistic effects were exhibited on amoxicillin plus quercetin and penicillin plus kaempferol against these strains at FIC index 0.50 and <0.38 respectively. The synergistic activity of quercetin plus amoxicillin was confirmed by the viable count. This combination increased CM permeability, caused marked morphological, peptidoglycan and cytoplasmic membrane damage, increased protein amide I and II, but decreased fatty acid in bacterial cells. The quercetin had an inhibitory activity against β-lactamase. So, these findings are the first report that quercetin has the synergistic effect with amoxicillin against ARSE via four modes of actions, inhibit peptidoglycan synthesis and β-lactamases activity, increase CM permeability and protein amide I and II but decrease fatty acid in bacterial cells. Of course, this flavonol has the dominant potential to develop a brand-new collateral phytochemical agent plus amoxicillin to treat ARSE. Future work should focus on the bioavailability, efficacy and toxicity in animal and human studies, as well as, the synergistic effect on blood and tissue should be evaluated and achieved.

  3. Challenges for a cross-disciplinary geoarchaeology: The intersection between environmental history and geomorphology

    Science.gov (United States)

    Butzer, Karl W.

    2008-10-01

    Geoarchaeology is a growing subfield of cross-disciplinary research at the intersection between geomorphology, environmental history, and archaeology. This prospective essay does not aim to analyze the nature or evolution of geoarachaeology, or to review available techniques and methods. Instead it addresses challenges. Exciting challenges confront geoarchaeology in the form of persistent problems that demand satisfactory solutions, despite improving skills and innovative technologies. Drawing from the full record of human history, a number of practical issues can be highlighted to explicate these challenges: Open-air archaeological sites are the main object of study for the Early to Mid-Pleistocene, even though they represent open systems that raise fundamental questions about archaeo-taphonomic integrity. How were sites buried and then modified by selective preservation, horizontal or vertical disturbance, and the role of carnivores? Is it possible to determine the degree to which such sites accurately record prehistoric human behavior, prior to the Late Pleistocene when hearths and living structures lend better definition to occupation surfaces? Can non-primary open-air sites also shed light on human activities and environmental history? Cave sites have long been favored by archaeologists because of the impression that they represent relatively complete and undisturbed archaeostratigraphic sequences. But serious problems also exist here in regard to the nature of accumulation and the sources of mineral and biogenic sediments in what were open systems, liable to disturbance, despite comparatively low-energy processes. Less familiar are urban and other architectural sites, where processes of formation and degradation mimic natural sedimentation and erosion. Such a geoarchaeology can be highly informative for urban processes, demographic cycles, or the intersection between sites and their surrounding landscapes. Spatial components of geoarchaeological research need

  4. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  5. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  6. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  7. Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.

    Science.gov (United States)

    Klaus, Haagen D

    2014-10-01

    Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. Copyright © 2014 Wiley Periodicals, Inc.

  8. Differential scanning fluorometry signatures as indicators of enzyme inhibitor mode of action: case study of glutathione S-transferase.

    Directory of Open Access Journals (Sweden)

    Wendy A Lea

    Full Text Available Differential scanning fluorometry (DSF, also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH. Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization.

  9. Graphene-Borate as an Efficient Fire Retardant for Cellulosic Materials with Multiple and Synergetic Modes of Action.

    Science.gov (United States)

    Nine, Md J; Tran, Diana N H; Tung, Tran Thanh; Kabiri, Shervin; Losic, Dusan

    2017-03-22

    To address high fire risks of flamable cellulosic materials, that can trigger easy combustion, flame propagation, and release of toxic gases, we report a new fire-retardant approach using synergetic actions combining unique properties of reduced graphene oxide (rGO) and hydrated-sodium metaborates (SMB). The single-step treatment of cellulosic materials by a composite suspension of rGO/SMB was developed to create a barrier layer on sawdust surface providing highly effective fire retardant protection with multiple modes of action. These performances are designed considering synergy between properties of hydrated-SMB crystals working as chemical heat-sink to slow down the thermal degradation of the cellulosic particles and gas impermeable rGO layers that prevents access of oxygen and the release of toxic volatiles. The rGO outer layer also creates a thermal and physical barrier by donating carbon between the flame and unburnt wood particles. The fire-retardant performance of developed graphene-borate composite and mechanism of fire protection are demonstrated by testing of different forms of cellulosic materials such as pine sawdust, particle-board, and fiber-based structures. Results revealed their outstanding self-extinguishing behavior with significant resistance to release of toxic and flammable volatiles suggesting rGO/SMB to be suitable alternative to the conventional toxic halogenated flame-retardant materials.

  10. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    Science.gov (United States)

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  11. Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R against Escherichia coli.

    Science.gov (United States)

    Machado, Diana; Fernandes, Laura; Costa, Sofia S; Cannalire, Rolando; Manfroni, Giuseppe; Tabarrini, Oriana; Couto, Isabel; Sabatini, Stefano; Viveiros, Miguel

    2017-01-01

    Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux in E. coli reducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of the E. coli inner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future

  12. Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R against Escherichia coli

    Directory of Open Access Journals (Sweden)

    Diana Machado

    2017-04-01

    Full Text Available Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-ylethoxy-2-(4-propoxyphenyl quinolone – PQQ4R, against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN and chlorpromazine (CPZ. The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux in E. coli reducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of the E. coli inner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF, dissipaters of PMF such as PQQ4R, can be

  13. Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.

    Science.gov (United States)

    Melnik, Bodo C

    2017-02-08

    Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.

  14. Antifungal modes of action of tea tree oil and its two characteristic components against Botrytis cinerea.

    Science.gov (United States)

    Yu, D; Wang, J; Shao, X; Xu, F; Wang, H

    2015-11-01

    The essential oil of Melaleuca alternifolia (tea tree) has been evaluated as a potential eco-friendly antifungal agent against Botrytis cinerea. In this study, we investigated the antifungal activity and mode of action of tea tree oil (TTO) and its components against B. cinerea. Of the components we tested in contact phase, terpinen-4-ol had the highest antifungal activity, followed by TTO, α-terpineol, terpinolene, then 1,8-cineole. As one of characteristic components of TTO, terpinen-4-ol treatment led to pronounced alterations in mycelial morphology, cellular ultrastructure, membrane permeability under scanning electron microscope, transmission electron microscope and fluorescent microscope, and also reduced the ergosterol content of fungi. As another characteristic component, 1,8-cineole caused serious intracellular damage but only slightly affected B. cinerea otherwise. When terpinen-4-ol and 1,8-cineole were used together, the synergistic antifungal activity was significantly higher than either component by itself. The results of our study confirmed that terpinen-4-ol and 1,8-cineole act mainly on the cell membranes and organelles of B. cinerea, respectively, and when combined are similar to TTO in antifungal activity due to their differences. Understanding the mechanism of terpinen-4-ol and 1,8-cineole antifungal action to B. cinerea is helpful for investigation on their synergistic effect and explaining antifungal action modes of TTO. © 2015 The Society for Applied Microbiology.

  15. Mode of action of the immunostimulatory effect of collagen from jellyfish.

    Science.gov (United States)

    Nishimoto, Sogo; Goto, Yoko; Morishige, Hitoshi; Shiraishi, Ryusuke; Doi, Mikiharu; Akiyama, Koichi; Yamauchi, Satoshi; Sugahara, Takuya

    2008-11-01

    We have previously demonstrated that collagen from jellyfish simulated immunoglobulin and cytokine production by human-human hybridoma line HB4C5 cells and by human peripheral blood lymphocytes (hPBL). The mode of action of the collagen as an immunostimulatory factor was investigated. The expression levels of immunoglobulin mRNAs in HB4C5 cells, and those of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta in hPBL were up-regulated by jellyfish collagen. In addition, this collagen activated IgM production by transcription-suppressed HB4C5 cells that had been treated with actinomycin D. This collagen also enhanced IgM production by translation-suppressed HB4C5 cells that had been treated with sodium fluoride, but was ineffective in accelerating IgM production by HB4C5 cells treated with cycloheximide. Moreover, the intracellular IgM level in HB4C5 cells treated with the post-translation inhibitor, monensin, was increased by this collagen. These results suggest that collagen from jellyfish stimulated not only the transcription activity, but also the translation activity for enhanced immunoglobulin and cytokine production.

  16. Nonphotodynamic Roles of Methylene Blue: Display of Distinct Antimycobacterial and Anticandidal Mode of Actions

    Directory of Open Access Journals (Sweden)

    Rahul Pal

    2018-01-01

    Full Text Available Significance of methylene blue (MB in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB against Candida albicans. The present study attempts to identify additional antimicrobial effect of MB against another prevalent human pathogen, Mycobacterium tuberculosis (MTB. We explored that MB is efficiently inhibiting the growth of Mycobacterium at 15.62 μg/ml albeit in bacteriostatic manner similar to its fungistatic nature. We uncovered additional cell surface phenotypes (colony morphology and cell sedimentation rate which were impaired only in Mycobacterium. Mechanistic insights revealed that MB causes energy dependent membrane perturbation in both C. albicans and Mycobacterium. We also confirmed that MB leads to enhanced reactive oxygen species generation in both organisms that could be reversed upon antioxidant supplementation; however, DNA damage could only be observed in Mycobacterium. We provided evidence that although biofilm formation was disrupted in both organisms, cell adherence to human epithelial cells was inhibited only in Mycobacterium. Lastly, RT-PCR results showed good correlation with the biochemical assay. Together, apart from the well-established role of MB in photodynamic therapy, this study provides insights into the distinct antimicrobial mode of actions in two significant human pathogens, Candida and Mycobacterium, which can be extrapolated to improve our understanding of finding novel therapeutic options.

  17. Modes of action for biological control of Botrytis cinerea by antagonistic bacteria

    Directory of Open Access Journals (Sweden)

    Rana HAIDAR

    2017-01-01

    Full Text Available The role of beneficial bacteria in biocontrol of plant diseases, particularly those caused by the necrotrophic fungus Botrytis cinerea, has been investigated by testing many bacteria under laboratory and field conditions. Bacteria may protect plants against B. cinerea by direct antagonistic interactions between biocontrol agents and this pathogen, as well as indirect effects through the induction of host resistance. This review focuses on various bacteria that act as biological control agents (BCAs of B. cinerea and their associated mechanisms. The modes of action (MoAs include: i synthesis of anti-fungal metabolites, such as antibiotics, cell wall-degrading enzymes and volatile organic compounds (VOCs; ii competition for nutrients and/or a niche; and iii induction of host resistance. The challenge for development of BCAs is to reduce the variability of efficiency and to prove persistence under a large range of conditions. We discuss the advantages and drawbacks of MoA for future applications of bacteria in the field and in post-harvest storage, as well as combination of different MoAs as a strategy to achieve a more regular efficacy.

  18. Duration of activity and mode of action of modafinil: Studies on sleep and wakefulness in humans.

    Science.gov (United States)

    Turner, C; Belyavin, A J; Nicholson, A N

    2014-07-01

    The duration of activity of modafinil was investigated in healthy male volunteers in two double-blind crossover studies. Mode of action was explored using a statistical model concerned with the relationship between total sleep duration and that of rapid eye movement (REM) sleep. Nocturnal sleep (23:00-07:00) followed by next-day performance (09:00-17:00) was studied in 12 subjects administered 100, 200, 300 mg modafinil and placebo, 0.5 h before bedtime. Performance overnight (19:00-08:45) followed by sleep (09:15-15:15) was studied in nine subjects administered 100, 200, 300, 400 mg modafinil, 300 mg caffeine and placebo at 22:15. Modafinil dose-dependently reduced sleep duration (nocturnal: 200 mg, pmodafinil during overnight work varied with dose (200 mg>100 mg; 300, 400 mg>200, 100 mg, caffeine). However, in the study of next-day performance, the enhancement was attenuated at the highest dose (300 mg) by the greater disturbance of prior sleep. These findings indicate that modafinil has a long duration of action, with alerting properties arising predominantly from dopaminergic activity. © The Author(s) 2013.

  19. Improved health and growth of fish fed mannan oligosaccharides: potential mode of action.

    Science.gov (United States)

    Torrecillas, Silvia; Montero, Daniel; Izquierdo, Marisol

    2014-02-01

    Nowadays, aquaculture industry still confronts several disease-related problems mainly caused by viruses, bacteria and parasites. In the last decade, the use of mannan oligosaccharides (MOS) in fish production has received increased attention due to its beneficial effects on fish performance and disease resistance. This review shows the MOS use in aquaculture with a specific emphasis on the effectiveness of the several MOS forms available in the market related to disease resistance, fish nutrition and the possible mechanisms involved. Among the main beneficial effects attributed to MOS dietary supplementation, enhanced fish performance, feed efficiency and pathogen protection by potentiation of the systemic and local immune system and the reinforcement of the epithelial barrier structure and functionality are some of the most commonly demonstrated benefits. These combined effects suggest that the reinforcement of the intestinal integrity and functionality, together with the stimulation of the innate immune system, are the primary mode of action of MOS in fish. However, the supplementation strategy related to the structure of the MOS added, the correct dose and duration, as well as fish species, size and culture conditions are determinant factors to achieve improvements in health status and growth performance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Coral snake venoms: mode of action and pathophysiology of experimental envenomation

    Directory of Open Access Journals (Sweden)

    Oswald Vital Brazil

    1987-06-01

    Full Text Available Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins, M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect. The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.

  1. Maggot therapy´s modes of action : effect of maggot secretions on microbiological, haematological and immunological processes

    NARCIS (Netherlands)

    Plas, Maartje Jeriena Adriana van der

    2009-01-01

    The work described in this thesis focussed on the modes of action of maggot therapy in chronic wounds, especially related to the inflammatory phase of wound healing. For this purpose, the effect of maggot excretions and/or secretions on microbiological, haematological and immunological processes was

  2. Evaluation of key events in the mode of action for a carry-over carcinogen in mice

    Science.gov (United States)

    Evaluation of key events in the mode of action for a carry-over carcinogen in mice Charles E. Wood, April D. Lake, Greg Olson, Michael H. George, Susan D. Hester, Anthony B. DeAngelo Introduction: Early life environmental exposures are established determinants for adverse health...

  3. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors-abstract

    Science.gov (United States)

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity but MoA classification in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity mode of action using a recently published dataset contain...

  4. Anti-Candida albicans effectiveness of citral and investigation of mode of action.

    Science.gov (United States)

    Lima, Igara Oliveira; de Medeiros Nóbrega, Fernanda; de Oliveira, Wylly Araújo; de Oliveira Lima, Edeltrudes; Albuquerque Menezes, Everardo; Cunha, Francisco Afrânio; Formiga Melo Diniz, Margareth de Fátima

    2012-12-01

    Candidiasis is a mycosis caused by Candida species, which is of clinical importance due to the increase in resistant yeasts. Candida infection has been a serious health problem due to the inappropriate use of antibiotics. Therefore, it is necessary to study molecules with an antifungal action. Citral is a monoterpene with known pharmacological properties, including antimicrobial action. The aim of this work was to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of citral and the probable mode of action. The MIC of citral was determined by the broth microdilution method using Sabouraud dextrose medium. Additionally, the interference of citral in cell wall (sorbitol assay) and the binding of citral to ergosterol and cholesterol were studied, carried out by broth microdilution method. The MIC and MFC of citral were 512 and 1024 µg/mL, respectively. The MIC of amphotericin B was 1 µg/mL. The mechanism of action did not involve either the cell wall or ergosterol. However, the presence of cholesterol increased the MIC of citral to 1024 µg/mL, indicating there is some interaction between citral and cholesterol. Amphotericin B was used as the positive control, and it showed a high MIC in the presence of ergosterol (32 µg/mL), while in the presence of cholesterol MIC increased to 4 µg/mL. Citral inhibits the growth of C. albicans. The probable mechanism of action did not involve the cell wall or ergosterol. Citral is able to interact with cholesterol. More studies are necessary to describe their effects completely.

  5. The Two-Peptide (Class-IIb) Bacteriocins: Genetics, Biosynthesis, Structure, and Mode of Action

    Science.gov (United States)

    Nissen-Meyer, Jon; Oppegård, Camilla; Rogne, Per; Haugen, Helen Sophie; Kristiansen, Per Eugen

    The two-peptide (class-IIb) bacteriocins consist of two different peptides, both of which are required to obtain high antimicrobial activity. These bacteriocins kill target-cells by inducing membrane-leakage and they seem to display some specificity with respect to the molecules they transfer across membranes. The genes encoding the two peptides of two-peptide bacteriocins are next to each other on the same operon. In the same or a nearby operon are genes encoding (i) the immunity protein that protects the bacteriocin-producer from its own bacteriocin, (ii) a dedicated ABC-transporter that exports the bacteriocin from cells and cleaves off the N-terminal bacteriocin leader sequence, and (iii) an accessory protein whose exact function has not been fully clarified. Some two-peptide bacteriocins appear to be produced constitutively, whereas the production of other two-peptide bacteriocins is regulated through a three-component regulatory system that consists of a peptide pheromone, a membrane-associated histidine protein kinase, and response regulators. It has recently been proposed that the two peptides of (some) two-peptide bacteriocins may form a membrane-penetrating helix-helix structure involving helix-helix interacting GxxxG-motifs present in all currently characterized two-peptide bacteriocins. It has also been suggested that the helix-helix structure interacts with an integrated membrane (transport) protein, thus inducing a conformational change in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to that of the pediocin-like (class-IIa) bacteriocins and lactococcin A, which bind to a part of the mannose phosphotransferase permease that is embedded in the cell membrane, thereby altering the conformation of the ­permease in a manner that causes membrane-leakage and cell death.

  6. Spray dried plasma as an alternative to antibiotics in piglet feeds, mode of action and biosafety.

    Science.gov (United States)

    Pérez-Bosque, Anna; Polo, Javier; Torrallardona, David

    2016-01-01

    The use of growth promoting and therapeutic antibiotics in piglet feed has been a concerning subject over the last few decades because of the risk of generating antimicrobial resistance that could be transferred to humans. As a result, many products have been proposed as potential alternatives to the use of antibiotics, and among these, spray dried plasma is considered one of the most promising. However, there have been concerns about its biosafety, particularly during periods of emergence or re-emergence of swine diseases in different regions of the world, such as the recent porcine epidemic diarrhea virus outbreak in North America. The objectives of this paper are to review recent publications about the use of spray dried plasma as an alternative to antibiotics in weaned pig diets, the possible mechanisms of action of spray dried plasma, and the existing evidence related to the biosafety of spray dried animal plasma. Particular attention is given to studies in which spray dried plasma has been directly compared to antibiotics or other alternative antimicrobial products. Several studies on the possible modes of action for spray dried plasma, such as preservation of gut barrier function or modulation of the immune response, are also reviewed. Finally, the paper focuses on the review of the existing studies on the risks of disease transmission with the use of spray dried plasma from porcine origin. Overall, spray dried plasma is a promising alternative to in-feed antimicrobials for piglets, particularly during the early stages of the post-weaning phase. Additionally, there is enough evidence to support that commercial spray dried porcine plasma is a safe product for pigs.

  7. Pleuromutilins: Potent Drugs for Resistant Bugs-Mode of Action and Resistance.

    Science.gov (United States)

    Paukner, Susanne; Riedl, Rosemarie

    2017-01-03

    use in veterinary medicine. This review focuses on the structural characteristics, mode of action, antibacterial activity, and resistance development of this potent and novel antibacterial class for systemic use in humans. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Neurotoxicity and mode of action of N, N-diethyl-meta-toluamide (DEET.

    Directory of Open Access Journals (Sweden)

    Daniel R Swale

    Full Text Available Recent studies suggest that N, N-diethyl-meta-toluamide (DEET is an acetylcholinesterase inhibitor and that this action may result in neurotoxicity and pose a risk to humans from its use as an insect repellent. We investigated the mode of action of DEET neurotoxicity in order to define the specific neuronal targets related to its acute toxicity in insects and mammals. Although toxic to mosquitoes (LD50 ca. 1.5 µg/mg, DEET was a poor acetylcholinesterase inhibitor (<10% inhibition, even at a concentration of 10 mM. IC50 values for DEET against Drosophila melanogaster, Musca domestica, and human acetylcholinesterases were 6-12 mM. Neurophysiological recordings showed that DEET had excitatory effects on the housefly larval central nervous system (EC50: 120 µM, but was over 300-fold less potent than propoxur, a standard anticholinesterase insecticide. Phentolamine, an octopamine receptor antagonist, completely blocked the central neuroexcitation by DEET and octopamine, but was essentially ineffective against hyperexcitation by propoxur and 4-aminopyridine, a potassium channel blocker. DEET was found to illuminate the firefly light organ, a tissue utilizing octopamine as the principal neurotransmitter. Additionally, DEET was shown to increase internal free calcium via the octopamine receptors of Sf21 cells, an effect blocked by phentolamine. DEET also blocked Na(+ and K(+ channels in patch clamped rat cortical neurons, with IC50 values in the micromolar range. These findings suggest DEET is likely targeting octopaminergic synapses to induce neuroexcitation and toxicity in insects, while acetylcholinesterase in both insects and mammals has low (mM sensitivity to DEET. The ion channel blocking action of DEET in neurons may contribute to the numbness experienced after inadvertent application to the lips or mouth of humans.

  9. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Valeria P Sülsen

    Full Text Available Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin

  10. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi.

    Science.gov (United States)

    Sülsen, Valeria P; Puente, Vanesa; Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S; Frank, Fernanda M; Lombardo, María E

    2016-01-01

    Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic

  11. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi

    Science.gov (United States)

    Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S.; Frank, Fernanda M.; Lombardo, María E.

    2016-01-01

    Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its

  12. Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

    Science.gov (United States)

    Yeager, R Philip; Kushman, Mary; Chemerynski, Susan; Weil, Roxana; Fu, Xin; White, Marcella; Callahan-Lyon, Priscilla; Rosenfeldt, Hans

    2016-06-01

    This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US.

  13. Differential Gel Electrophoresis (DIGE Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes.

    Directory of Open Access Journals (Sweden)

    Giselle Villa Flor Brunoro

    2016-08-01

    Full Text Available The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite.The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase.Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.

  14. Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes

    Science.gov (United States)

    Brunoro, Giselle Villa Flor; Faça, Vitor Marcel; Caminha, Marcelle Almeida; Ferreira, André Teixeira da Silva; Trugilho, Monique; de Moura, Kelly Cristina Gallan; Perales, Jonas; Valente, Richard Hemmi; Menna-Barreto, Rubem Figueiredo Sadok

    2016-01-01

    Background The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite. Methodology/Principal Findings The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase. Conclusion/Significance Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents. PMID:27551855

  15. Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes.

    Science.gov (United States)

    Brunoro, Giselle Villa Flor; Faça, Vitor Marcel; Caminha, Marcelle Almeida; Ferreira, André Teixeira da Silva; Trugilho, Monique; de Moura, Kelly Cristina Gallan; Perales, Jonas; Valente, Richard Hemmi; Menna-Barreto, Rubem Figueiredo Sadok

    2016-08-01

    The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite. The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase. Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.

  16. Mode of action associated with development of hemangiosarcoma in mice given pregabalin and assessment of human relevance.

    Science.gov (United States)

    Criswell, Kay A; Cook, Jon C; Wojcinski, Zbigniew; Pegg, David; Herman, James; Wesche, David; Giddings, John; Brady, Joseph T; Anderson, Timothy

    2012-07-01

    Pregabalin increased the incidence of hemangiosarcomas in carcinogenicity studies of 2-year mice but was not tumorigenic in rats. Serum bicarbonate increased within 24 h of pregabalin administration in mice and rats. Rats compensated appropriately, but mice developed metabolic alkalosis and increased blood pH. Local tissue hypoxia and increased endothelial cell proliferation were also confirmed in mice alone. The combination of hypoxia and sustained increases in endothelial cell proliferation, angiogenic growth factors, dysregulated erythropoiesis, and macrophage activation is proposed as the key event in the mode of action (MOA) for hemangiosarcoma formation. Hemangiosarcomas occur spontaneously in untreated control mice but occur only rarely in humans. The International Programme on Chemical Safety and International Life Sciences Institute developed a Human Relevance Framework (HRF) analysis whereby presence or absence of key events can be used to assess human relevance. The HRF combines the MOA with an assessment of biologic plausibility in humans to assess human relevance. This manuscript compares the proposed MOA with Hill criteria, a component of the HRF, for strength, consistency, specificity, temporality, and dose response, with an assessment of key biomarkers in humans, species differences in response to disease conditions, and spontaneous incidence of hemangiosarcoma to evaluate human relevance. Lack of key biomarker events in the MOA in rats, monkeys, and humans supports a species-specific process and demonstrates that the tumor findings in mice are not relevant to humans at the clinical dose of pregabalin. Based on this collective dataset, clinical use of pregabalin would not pose an increased risk for hemangiosarcoma to humans.

  17. Ruby laser-assisted depilation: The mode of action and potential ways of improved outcome

    Science.gov (United States)

    Topping, Adam Partington

    Aim - To improve efficacy and lessen side effects resulting from normal mode ruby laser (NMRL)-assisted depilation via a greater understanding of its mode of action and the development of novel methods of reducing associated epidermal damage. Employing a thermal imaging camera and ex vivo hair-bearing skin, the targets for the NMRL (pulse duration 900 musec and spot size 7 mm) were defined, the temperatures reached and the heat dissipation rates determined. Production of heat was confined to the hair follicles, with the peak temperatures reached varying considerably between hairs within the same treatment area and also between individuals. Histological assessment for a known indicator of cellular damage (p53 expression) identified the sites and extent of damage, which correlated with the peak temperatures measured. An energy meter was used to detect the penetration of NMRL light through ex vivo skin, which was found to be deeper than previously theorised. The black-haired mouse (C57B1/10) was assessed both macroscopically and histologically and found to be an acceptable animal model of NMRL depilation and associated epidermal damage. Attempts to reduce the epidermal damage by simply stopping the light reaching the epidermis using a chromophore block were assessed. Chromophore did indeed reduce the amount of epidermal damage detected in laser-irradiated ex vivo human skin, whereas in contrast it increased the wounding seen in the much thinner skin of the mouse. Nevertheless the mouse model showed that this technique did not affect the depilation efficacy. An alternative method of reducing epidermal damage using induction of the cells' intrinsic protective mechanisms (heat shock proteins, HSP) was assessed using cultured keratinocytes and the mouse model. Primarily, the sub-lethal temperature optimum for HSP expression in human keratinocytes was determined, then an in vitro model of NMRL-associated epidermal damage was established and the heat pre-treatment assessed

  18. An integrated approach for prospectively investigating a mode-of-action for rodent liver effects

    Energy Technology Data Exchange (ETDEWEB)

    LeBaron, Matthew J., E-mail: MJLeBaron@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Geter, David R., E-mail: dave.geter@gmail.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Rasoulpour, Reza J. [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Gollapudi, B. Bhaskar, E-mail: BBGollapudi@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Thomas, Johnson, E-mail: JThomas4@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Murray, Jennifer, E-mail: AMurray@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Kan, H. Lynn, E-mail: HLKan@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Wood, Amanda J., E-mail: AJWood@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Elcombe, Cliff, E-mail: CliffElcombe@cxrbiosciences.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Vardy, Audrey, E-mail: audrey_vardy@europe.bd.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); McEwan, Jillian, E-mail: jillian.mcewan@rtmcewan.co.uk [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Terry, Claire, E-mail: CTerry@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom); Billington, Richard, E-mail: RBillington@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom)

    2013-07-15

    Registration of new plant protection products (e.g., herbicide, insecticide, or fungicide) requires comprehensive mammalian toxicity evaluation including carcinogenicity studies in two species. The outcome of the carcinogenicity testing has a significant bearing on the overall human health risk assessment of the substance and, consequently, approved uses for different crops across geographies. In order to understand the relevance of a specific tumor finding to human health, a systematic, transparent, and hypothesis-driven mode of action (MoA) investigation is, appropriately, an expectation by the regulatory agencies. Here, we describe a novel approach of prospectively generating the MoA data by implementing additional end points to the standard guideline toxicity studies with sulfoxaflor, a molecule in development. This proactive MoA approach results in a more robust integration of molecular with apical end points while minimizing animal use. Sulfoxaflor, a molecule targeting sap-feeding insects, induced liver effects (increased liver weight due to hepatocellular hypertrophy) in an initial palatability probe study for selecting doses for subsequent repeat-dose dietary studies. This finding triggered the inclusion of dose-response investigations of the potential key events for rodent liver carcinogenesis, concurrent with the hazard assessment studies. As predicted, sulfoxaflor induced liver tumors in rats and mice in the bioassays. The MoA data available by the time of the carcinogenicity finding supported the conclusion that the carcinogenic potential of sulfoxaflor was due to CAR/PXR nuclear receptor activation with subsequent hepatocellular proliferation. This MoA was not considered to be relevant to humans as sulfoxaflor is unlikely to induce hepatocellular proliferation in humans and therefore would not be a human liver carcinogen. - Highlights: • We prospectively generated MoA data into standard guideline toxicity studies. • A proactive MoA approach

  19. Using Mode of Action to Assess Health Risks from Mixtures of Chemical/Physical Agents

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Richard J.; Lei, Xingye C.; Sasser, Lyle B.

    2003-01-20

    Interactions between tumor promoters with differing mechanisms of action were examined in male B6C3F1 mice treated with mixtures of dichloroacetate (DCA), trichloroacetate (TCA), and tetrachloride (CT), each of which acts by a different mode of action. Mice were initiated by vinyl carbamate (VC), and then promoted by DCA, TCA, CT, or the pair-wised combinations of the three compounds. The effect of each treatment or treatment combination on tumor number/animal and tumor size was individually assessed at 18, 24, 30 or 36 weeks of treatment. Dose-related increases in tumor size were observed with 20 & 50 mg/kg CT, but each produced equal number of tumors at 36 weeks with the main distinction being a decrease in tumor latency at the higher dose. Overall TCA treatment produced dose-related increases in tumor number at 36 weeks of treatment. Thus, the lower doses of CT and TCA treatments apparently affected tumor size rather than number. Results with DCA were not as clear as a true maximum tumor number was not clearly observed within the experimental period. Treatment of mice receiving a high dose of TCA (2 g/L of drinking water) combined with varying doses of DCA (0.1, 0.5 and 2 g/L) produced increased numbers of tumors at 24 weeks and 36 weeks. However, at 36 weeks of treatment DCA produced a dose-related decrease in the size of tumors promoted by TCA. The low dose of TCA (0.1 g/L) decreased the number of tumors produced by a high dose of DCA, however, higher doses of TCA produced the same number as observed with DCA alone. Since these two chemicals produce lesions with differing phenotypes, the combination would have been expected to be additive with respect to number, but this was obviously not the case. These data suggest that the induction of liver cancer from mixtures of solvents may have predictable outcomes. The major conclusion is that these interactions are generally no more than additive. It was most interesting to note that additivity was only observed when

  20. An evaluation of the mode of action framework for mutagenic carcinogens case study: Cyclophosphamide.

    Science.gov (United States)

    McCarroll, Nancy; Keshava, Nagalakshmi; Cimino, Michael; Chu, Margaret; Dearfield, Kerry; Keshava, Channa; Kligerman, Andrew; Owen, Russell; Protzel, Alberto; Putzrath, Resha; Schoeny, Rita

    2008-03-01

    In response to the 2005 revised US Environmental Protection Agency (EPA) Cancer Guidelines, a Risk Assessment Forum's Technical Panel has devised a strategy in which genetic toxicology data combined with other information are assessed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent adjustment factors (ADAFs) should be applied to the cancer risk assessment. A decision tree has been developed as a part of this approach and outlines the critical steps for analyzing a compound for carcinogenicity through a mutagenic MOA (e.g., data analysis, determination of mutagenicity in animals and in humans). Agents, showing mutagenicity in animals and humans, proceed through the Agency's framework analysis for MOAs. Cyclophosphamide (CP), an antineoplastic agent, which is carcinogenic in animals and humans and mutagenic in vitro and in vivo, was selected as a case study to illustrate how the framework analysis would be applied to prove that a carcinogen operates through a mutagenic MOA. Consistent positive results have been seen for mutagenic activity in numerous in vitro assays, in animals (mice, rats, and hamsters) and in humans. Accordingly, CP was processed through the framework analysis and key steps leading to tumor formation were identified as follows: metabolism of the parent compound to alkylating metabolites, DNA damage followed by induction of multiple adverse genetic events, cell proliferation, and bladder tumors. Genetic changes in rats (sister chromatid exchanges at 0.62 mg/kg) can commence within 30 min and in cancer patients, chromosome aberrations at 35 mg/kg are seen by 1 hr, well within the timeframe and tumorigenic dose range for early events. Supporting evidence is also found for cell proliferation, indicating that mutagenicity, associated with cytotoxicity, leads to a proliferative response, which occurs early (48 hr) in the process of tumor induction

  1. Probiotic lactic acid bacteria in the gastro-intestinal tract: health benefits, safety and mode of action.

    Science.gov (United States)

    Dicks, L M T; Botes, M

    2010-03-01

    Lactic acid bacteria (LAB) have received considerable attention as probiotics over the past few years. This concept has grown from traditional dairy products to a profitable market of probiotic health supplements and functional foods. Extensive research is done on novel potential probiotic strains, with specific emphasis on their health benefits and mode of action. Criteria for the selection of probiotic strains have only recently been formulated by the Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO). Several in vitro techniques have been developed to evaluate the probiotic properties of strains. In many cases, this is followed by in vivo tests. Safety studies are also obligatory, as a few cases of bacteremia caused by LAB have been reported. This review focuses on the health benefits and safety of LAB probiotics, the criteria used to select a probiotic, mode of action and the impact these organisms have on natural microbiota in the gastro-intestinal tract.

  2. Mode of action of poly(vinylpyridine-N-oxide) in preventing silicosis: Effective scavenging of carbonate anion radical

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, S.; Czapski, G.; Heller, A. [Hebrew University of Jerusalem, Jerusalem (Israel). Dept. of Physical Chemistry

    2006-01-15

    Inhalation of quartz crystallites causes silicosis, a devastating lung disease afflicting miners, particularly coal and stone workers. Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and treatment of silicosis, but their mode of action has been obscure. Here, we show that PVPNOs do not react with peroxynitrite but scavenge exceptionally rapidly carbonate radicals, which are produced in the decomposition of ONOO- in bicarbonate solutions.

  3. Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Evelien Gerits

    Full Text Available Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino-3-(3,6-dichloro-9H-carbazol-9-ylpropan-2-ol, which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies.

  4. Cross-disciplinary working in the sciences and humanities: historical data rescue activities in Southeast Asia and beyond

    Science.gov (United States)

    Williamson, Fiona

    2016-12-01

    This paper argues that more work is needed to facilitate cross-disciplinary collaborations by scholars across the physical sciences and humanities to improve Data Rescue Activities (DARE). Debate over the scale and potential impact of anthropogenic global warming is one of the dominant narratives of the twenty-first century. Predicting future climates and determining how environment and society might be affected by climate change are global issues of social, economic and political importance. They require responses from different research communities and necessitate closer inter-disciplinary working relationships for an integrated approach. Improving the datasets required for long-term climate models is an important part of this process. Establishing a multi-disciplinary dialogue and approach to DARE activities is increasingly being recognised as the best way to achieve this. This paper focuses on the recovery of the long-term instrumental weather observations used for models and reconstructions of the climate over the past two-hundred years. Written from the perspective of an historian working in the field, it does not seek to explore the reconstructions themselves but the process of data gathering, advocating a closer working relationship between the arts, social sciences, and sciences to extend the geographic and temporal coverage of extant datasets. This is especially important for regions where data gaps exist currently. First, it will offer a justification for extending data recovery activities for Southeast Asia and the China Seas region. Second, it will offer a brief overview of the data recovery projects currently operating in that area and the typesof historic source material that are used. Third, it will explore the work currently being undertaken for Southeast Asia and China under the Atmospheric Circulation Reconstructions over the Earth initiative as an example of a successful cross-disciplinary program. Finally, it will argue the importance of

  5. Mode of action based risk assessment of the botanical food-borne alkenylbenzenesapiol and myristicin

    NARCIS (Netherlands)

    Alajlouni, Abdul

    2017-01-01

    Alkenylbenzenes including estragole, methyleugenol, safrole, elemicin, apiol, and myristicin are naturally occurring in many herbs such as parsley, dill, basil, tarragon, fennel and nutmeg (Kreydiyyeh and Usta, 2002, Smith et al., 2002, Semenov et al., 2007). Estragole, methyleugenol and safrole are

  6. Machine Learning and Molecular Dynamics Based Insights into Mode of Actions of Insulin Degrading Enzyme Modulators.

    Science.gov (United States)

    Jamal, Salma; Goyal, Sukriti; Shanker, Asheesh; Grover, Abhinav

    2017-01-01

    Alzheimer's disease (AD) is one of the most common lethal neurodegenerative disorders having impact on the lives of millions of people worldwide. The disease lacks effective treatment options and the unavailability of the drugs to cure the disease necessitates the development of effectual anti-Alzheimer drugs. Several mechanisms have been reported underlying the association of the two disorders, diabetes and dementia, one among which is the insulin-degrading enzyme (IDE) which is known to degrade insulin as well beta-amyloid peptides. The present study is aimed to generate accurate classification models using machine learning techniques, which could identify IDE modulators from a bioassay dataset consisting of IDE inhibitors as well as non-inhibitors. The identified compounds were subjected to docking and Molecular dynamics (MD) studies for an in-depth analysis of the binding modes along with the complex stability. This study proposes that the identified potential active compounds, STK026154 (PubChem ID: CID2927418) with Glide score of -7.70 kcal/mol and BAS05901102 (PubChem ID: CID3152845) with Glide score of -7.06 kcal/mol, could serve as promising leads for the development of novel drugs against AD. The present study shows that such in silico approaches can be effectively used to discover and select active compounds from unseen data for accelerated drug development process. The machine learning models generated in the present study were used to screen Traditional Chinese Medicine (TCM) database to identify the phytocompounds already been reported to have therapeutic effects against AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Structure-based discovery of novel US28 small molecule ligands with different modes of action

    DEFF Research Database (Denmark)

    Lückmann, Michael; Amarandi, Roxana-Maria; Papargyri, Natalia

    2017-01-01

    The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor, which can recognize various chemokines. Despite the recent determination of its 2.9 angstrom crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural...

  8. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.

    Science.gov (United States)

    Simon-Delso, N; Amaral-Rogers, V; Belzunces, L P; Bonmatin, J M; Chagnon, M; Downs, C; Furlan, L; Gibbons, D W; Giorio, C; Girolami, V; Goulson, D; Kreutzweiser, D P; Krupke, C H; Liess, M; Long, E; McField, M; Mineau, P; Mitchell, E A D; Morrissey, C A; Noome, D A; Pisa, L; Settele, J; Stark, J D; Tapparo, A; Van Dyck, H; Van Praagh, J; Van der Sluijs, J P; Whitehorn, P R; Wiemers, M

    2015-01-01

    doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

  9. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors

    Energy Technology Data Exchange (ETDEWEB)

    Carriger, John F. [U.S. Environmental Protection Agency, Office of Research and Development, Gulf Ecology Division, Gulf Breeze, FL, 32561 (United States); Martin, Todd M. [U.S. Environmental Protection Agency, Office of Research and Development, Sustainable Technology Division, Cincinnati, OH, 45220 (United States); Barron, Mace G., E-mail: barron.mace@epa.gov [U.S. Environmental Protection Agency, Office of Research and Development, Gulf Ecology Division, Gulf Breeze, FL, 32561 (United States)

    2016-11-15

    Highlights: • A Bayesian network was developed to classify chemical mode of action (MoA). • The network was based on the aquatic toxicity MoA for over 1000 chemicals. • A Markov blanket algorithm selected a subset of theoretical molecular descriptors. • Sensitivity analyses found influential descriptors for classifying the MoAs. • Overall precision of the Bayesian MoA classification model was 80%. - Abstract: The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity, but development of predictive MoA classification models in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity MoA using a recently published dataset containing over one thousand chemicals with MoA assignments for aquatic animal toxicity. Two dimensional theoretical chemical descriptors were generated for each chemical using the Toxicity Estimation Software Tool. The model was developed through augmented Markov blanket discovery from the dataset of 1098 chemicals with the MoA broad classifications as a target node. From cross validation, the overall precision for the model was 80.2%. The best precision was for the AChEI MoA (93.5%) where 257 chemicals out of 275 were correctly classified. Model precision was poorest for the reactivity MoA (48.5%) where 48 out of 99 reactive chemicals were correctly classified. Narcosis represented the largest class within the MoA dataset and had a precision and reliability of 80.0%, reflecting the global precision across all of the MoAs. False negatives for narcosis most often fell into electron transport inhibition, neurotoxicity or reactivity MoAs. False negatives for all other MoAs were most often narcosis. A probabilistic sensitivity analysis was undertaken for each MoA to examine the sensitivity to individual and multiple descriptor findings. The results show that the Markov blanket of a structurally complex dataset can simplify analysis and interpretation by

  10. Appropriate Ventilation Solutions For The Iconographic Buildings From The Fifties - A Cross Disciplinary Investigation

    DEFF Research Database (Denmark)

    Vestergaard, Inge; Blyt, Henrik Jean

    2016-01-01

    : this integrated working methodology develops new renovation processes. Based on both quantitative measurements and on qualitative judgements the cases are analysed comparatively. Parameters such as ventilation solutions in facades are discussed as architectural consequence and value. User interviews will also...

  11. Cytotoxicity and modes of action of five Cameroonian medicinal plants against multi-factorial drug resistance of tumor cells.

    Science.gov (United States)

    Kuete, Victor; Tankeo, Simplice B; Saeed, Mohamed E M; Wiench, Benjamin; Tane, Pierre; Efferth, Thomas

    2014-04-11

    Beilschmiedia acuta Kosterm, Clausena anisata (Willd) Hook, Fagara tessmannii Engl., Newbouldia laevis Seem., and Polyscias fulva (Hiern) Harms. are medicinal plants used in Cameroonian traditional medicine in the treatment of various types of cancers. The present study aims at investigating 11 methanolic extracts from the above Cameroonian medicinal plants on a panel of human cancer cell lines, including various drug-resistant phenotypes. Possible modes of action were analyzed for two extracts from Beilschmiedia acuta and Polyscia fulva and alpha-hederin, the representative constituent of Polyscia fulva. Cytotoxicity was determined using a resazurin assay. Cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Cellular response to alpha-hederin was investigated by a mRNA microarray approach. Prescreening of extracts (40µg/mL) showed that three of eleven plant extracts inhibited proliferation of CCRF-CEM cells by more than 50%, i.e. BAL (73.65%), the bark extract of Beilschmiedia acuta (78.67%) and PFR (68.72%). Subsequent investigations revealed IC50 values below or around 30µg/mL of BAL and PFR in 10 cell lines, including drug-resistant models, i.e. P-glycoprotein-overexpressing CEM/ADR5000, breast cancer resistance protein-transfected MDA-MB-231-BCRP, TP53 knockout cells (HCT116 p53(-/-)), and mutation-activated epidermal growth factor receptor-transfected U87MG.ΔEGFR cells. IC50 values below 5µg/mL of BAL were obtained for HCT116 (p53(-/-)) cells. IC50 values below 10µM of alpha-hederin were found for sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cells. The BAL and PFR extracts induced cell cycle arrest between G0/G1 and S phases. PFR-induced apoptosis was associated with increased ROS generation and MMP breakdown. Microarray-based cluster analysis revealed a gene expression profile that predicted cellular response to alpha-hederin. BAL, PFL and alpha-hederin, an

  12. Use of Web Resources in the Journal Literature 2001 and 2007: A Cross-Disciplinary Study

    Science.gov (United States)

    Zhang, Li

    2011-01-01

    This article examines Web resources in research articles from 30 scholarly journals in disciplines across the sciences, social sciences, and humanities. The purpose of the study is to report the degree to which scholars make use of Web-based resources in the journal literature and to identify Web citation characteristics within different subject…

  13. Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action.

    Science.gov (United States)

    Targett-Adams, Paul; Graham, Emily J S; Middleton, Jenny; Palmer, Amy; Shaw, Stephen M; Lavender, Helen; Brain, Philip; Tran, Thien Duc; Jones, Lyn H; Wakenhut, Florian; Stammen, Blanda; Pryde, David; Pickford, Chris; Westby, Mike

    2011-07-01

    The current standard of care for hepatitis C virus (HCV)-infected patients consists of lengthy treatment with interferon and ribavirin. To increase the effectiveness of HCV therapy, future regimens will incorporate multiple direct-acting antiviral (DAA) drugs. Recently, the HCV-encoded NS5A protein has emerged as a promising DAA target. Compounds targeting NS5A exhibit remarkable potency in vitro and demonstrate early clinical promise, suggesting that NS5A inhibitors could feature in future DAA combination therapies. Since the mechanisms through which these molecules operate are unknown, we have used NS5A inhibitors as tools to investigate their modes of action. Analysis of replicon-containing cells revealed dramatic phenotypic alterations in NS5A localization following treatment with NS5A inhibitors; NS5A was redistributed from the endoplasmic reticulum to lipid droplets. The NS5A relocalization did not occur in cells treated with other classes of HCV inhibitors, and NS5A-targeting molecules did not cause similar alterations in the localization of other HCV-encoded proteins. Time course analysis of the redistribution of NS5A revealed that the transfer of protein to lipid droplets was concomitant with the onset of inhibition, as judged by the kinetic profiles for these compounds. Furthermore, analysis of the kinetic profile of inhibition for a panel of test molecules permitted the separation of compounds into different kinetic classes based on their modes of action. Results from this approach suggested that NS5A inhibitors perturbed the function of new replication complexes, rather than acting on preformed complexes. Taken together, our data reveal novel biological consequences of NS5A inhibition, which may help enable the development of future assay platforms for the identification of new and/or different NS5A inhibitors.

  14. Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT Scanning.

    Science.gov (United States)

    El-Sherief, Ahmed H; Lau, Charles T; Obuchowski, Nancy A; Mehta, Atul C; Rice, Thomas W; Blackstone, Eugene H

    2017-04-01

    Accurate and consistent regional lymph node classification is an important element in the staging and multidisciplinary management of lung cancer. Regional lymph node definition sets-lymph node maps-have been created to standardize regional lymph node classification. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a lymph node map to supersede all preexisting lymph node maps. Our aim was to study if and how lung cancer specialists apply the IASLC lymph node map when classifying thoracic lymph nodes encountered on CT scans during lung cancer staging. From April 2013 through July 2013, invitations were distributed to all members of the Fleischner Society, Society of Thoracic Radiology, General Thoracic Surgical Club, and the American Association of Bronchology and Interventional Pulmonology to participate in an anonymous online image-based and text-based 20-question survey regarding lymph node classification for lung cancer staging on CT imaging. Three hundred thirty-seven people responded (approximately 25% participation). Respondents consisted of self-reported thoracic radiologists (n = 158), thoracic surgeons (n = 102), and pulmonologists who perform endobronchial ultrasonography (n = 77). Half of the respondents (50%; 95% CI, 44%-55%) reported using the IASLC lymph node map in daily practice, with no significant differences between subspecialties. A disparity was observed between the IASLC definition sets and their interpretation and application on CT scans, in particular for lymph nodes near the thoracic inlet, anterior to the trachea, anterior to the tracheal bifurcation, near the ligamentum arteriosum, between the bronchus intermedius and esophagus, in the internal mammary space, and adjacent to the heart. Use of older lymph node maps and inconsistencies in interpretation and application of definitions in the IASLC lymph node map may potentially lead to misclassification of stage and suboptimal management of lung

  15. An integrated, cross-disciplinary study of soil hydrophobicity at atomic, molecular, core and landscape scales

    Science.gov (United States)

    Matthews, G. Peter; Doerr, Stefan; Van Keulen, Geertje; Dudley, Ed; Francis, Lewis; Whalley, Richard; Gazze, Andrea; Hallin, Ingrid; Quinn, Gerry; Sinclair, Kat; Ashton, Rhys

    2017-04-01

    Soil hydrophobicity can lead to reduced soil fertility and heightened flood risk caused by increased run-off. Soil hydrophobicity is a well-known phenomenon when induced by natural events such as wildfires and anthropogenic causes including adding organic wastes or hydrocarbon contaminants. This presentation concerns a much more subtle effect - the naturally occurring changes between hydrophilic and hydrophobic states caused by periods of wetness and drought. Although subtle, they nevertheless affect vast areas of soil, and so their effects can be very significant, and are predicted to increase under climate change conditions. To understand the effect, a major interdisciplinary study has been commissioned by the UK's Natural Environment Research Council (NERC) to investigate soil hydrophobicity over length scales ranging from atomic through molecular, core and landscape scale. We present the key findings from the many publications currently in preparation. The programme is predicated on the hypothesis that changes in soil protein abundance and localization, induced by variations in soil moisture and temperature, are crucial driving forces for transitions between hydrophobic and hydrophilic conditions at soil particle surfaces, and that these effects can be meaningfully upscaled from molecular to landscape scale. Three soils were chosen based on the severity of hydrophobicity that can be achieved in the field: severe to extreme (natural rough pasture, Wales), intermediate to severe (pasture, Wales), and subcritical (managed research grassland, Rothamsted Research, England). The latter is already highly characterised so was also used as a control. Hydrophobic/ hydrophilic transitions were determined from water droplet penetration times. Scientific advances in the following five areas will be described: (i) the identification of these soil proteins by proteomic methods, using novel separation methods which reduces interference by humic acids, and allows identification

  16. Mode of action of metabolites from Bacillus sp. strain IBA 33 on Geotrichum citri-aurantii arthroconidia.

    Science.gov (United States)

    Gordillo, María Antonieta; Navarro, Antonio R; Maldonado, María Cristina

    2015-11-01

    Geotrichum citri-aurantii is a postharvest phytopathogenic fungus of lemons. We studied the mode of action of antifungal metabolites from Bacillus sp. strain IBA 33 on arthroconidia of G. citri-aurantii. These metabolites are lipopeptides belonging to the iturin family. Membrane permeabilization of G. citri-aurantii was analyzed and mitochondrial respiratory rate was evaluated. Disturbance of the plasma membrane promotes the leakage of many cellular components into the surrounding media, and mitochondrial membrane disorganization promotes the inhibition of the respiratory rate. Our findings provide insights into the ability of lipopeptides to suppress plant fungal pathogens and their possible agronomical applications.

  17. Potential of plant essential oils and their components in animal agriculture – in vitro studies on antibacterial mode of action

    Directory of Open Access Journals (Sweden)

    Corliss A. O'bryan

    2015-09-01

    Full Text Available The broad field of agriculture is currently undergoing major changes in practices, with new catch phrases including organic and sustainable. Consumers are more aware than ever before of the food that they eat and they want food free of toxic chemicals, antibiotics and the like. The antimicrobial activity of essential oils and their components has been recognized for several years. Recent research has demonstrated that many of these essential oils have beneficial effects for livestock, including reduction of foodborne pathogens in these animals. Essential oils as natural antimicrobials offer the opportunity to help maintain the safety of our food supply and minimize consumers’ concerns about consumption of synthetic chemicals. Numerous studies have been made into the mode of action of essential oils and the resulting elucidation of bacterial cell targets have contributed to new perspectives on countering antimicrobial resistance and pathogenicity of these bacteria. In this review, after a brief discussion of the uses essential oils in agriculture as antimicrobials, we give an overview of the current knowledge about the antibacterial mode of action of essential oils and their constituents as determined in vitro.

  18. Proposed mechanism of antibacterial mode of action of Caesalpinia bonducella seed oil against food-borne pathogens

    Directory of Open Access Journals (Sweden)

    Shruti Shukla

    2016-03-01

    Full Text Available The antibacterial mechanism of action of Caesalpinia bonducella seed oil on membrane permeability of Listeria monocytogenes NCIM 24563 (MIC: 2 mg/mL and Escherichia coli ATCC 25922 (MIC: 4 mg/mL was determined by measuring the extracellular ATP concentration, release of 260-nm absorbing materials, leakage of potassium ions and measurement of relative electrical conductivity of the bacterial cells treated at MIC concentration. Its mode of action on membrane integrity was confirmed by release of extracellular ATP (1.42 and 1.33 pg/mL, loss of 260-nm absorbing materials (4.36 and 4.19 optical density, leakage of potassium ions (950 and 1000 mmol/L and increase in relative electrical conductivity (12.6 and 10.5% against food-borne pathogenic bacteria L. monocytogenes and E. coli, respectively. These findings propose that C. bonducella oil compromised its mode of action on membrane integrity, suggesting its enormous food and pharmacological potential.

  19. A Flow Cytometry Method for Rapidly Assessing Mycobacterium tuberculosis Responses to Antibiotics with Different Modes of Action.

    Science.gov (United States)

    Hendon-Dunn, Charlotte Louise; Doris, Kathryn Sarah; Thomas, Stephen Richard; Allnutt, Jonathan Charles; Marriott, Alice Ann Neville; Hatch, Kim Alexandra; Watson, Robert James; Bottley, Graham; Marsh, Philip David; Taylor, Stephen Charles; Bacon, Joanna

    2016-07-01

    Current methods for assessing the drug susceptibility of Mycobacterium tuberculosis are lengthy and do not capture information about viable organisms that are not immediately culturable under standard laboratory conditions as a result of antibiotic exposure. We have developed a rapid dual-fluorescence flow cytometry method using markers for cell viability and death. We show that the fluorescent marker calcein violet with an acetoxy-methyl ester group (CV-AM) can differentiate between populations of M. tuberculosis growing at different rates, while Sytox green (SG) can differentiate between live and dead mycobacteria. M. tuberculosis was exposed to isoniazid or rifampin at different concentrations over time and either dual stained with CV-AM and SG and analyzed by flow cytometry or plated to determine the viability of the cells. Although similar trends in the loss of viability were observed when the results of flow cytometry and the plate counting methods were compared, there was a lack of correlation between these two approaches, as the flow cytometry analysis potentially captured information about cell populations that were unable to grow under standard conditions. The flow cytometry approach had an additional advantage in that it could provide insights into the mode of action of the drug: antibiotics targeting the cell wall gave a flow cytometry profile distinct from those inhibiting intracellular processes. This rapid drug susceptibility testing method could identify more effective antimycobacterials, provide information about their potential mode of action, and accelerate their progress to the clinic. Copyright © 2016 Hendon-Dunn et al.

  20. Classification, mode of action and production strategy of xylanase and its application for biofuel production from water hyacinth.

    Science.gov (United States)

    Uday, Uma Shankar Prasad; Choudhury, Payel; Bandyopadhyay, Tarun Kanti; Bhunia, Biswanath

    2016-01-01

    Xylanases are classified under glycoside hydrolase families which represent one of the largest groups of commercial enzymes. Depolymerizing xylan molecules into monomeric pentose units involves the synergistic action of mainly two key enzymes which are endo-β-xylanase and β-xylosidase. Xylanases are different with respect to their mode of action, substrate specificities, biochemical properties, 3D structure and are widely produced by a spectrum of bacteria and fungi. Currently, large scale production of xylanase can be produced through the application of genetic engineering tool which allow fast identification of novel xylanase genes and their genetic variations makes it an ideal enzymes. Due to depletion of fossil fuel, there is urgent need to find out environment friendly and sustainable energy sources. Therefore, utilisation of cheap lignocellulosic materials along with proper optimisation of process is most important for cost efficient ethanol production. Among, various types of lignocellulosic substances, water hyacinth, a noxious aquatic weed, has been found in many tropical. Therefore, the technological development for biofuel production from water hyacinth is becoming commercially worthwhile. In this review, the classification and mode of action of xylanase including genetic regulation and strategy for robust xylanase production have been critically discussed from recent reports. In addition various strategies for cost effective biofuel production from water hyacinth including chimeric proteins design has also been critically evaluated. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.

    Science.gov (United States)

    Matsuda, Hisashi; Ninomiya, Kiyofumi; Morikawa, Toshio; Yasuda, Daisuke; Yamaguchi, Itadaki; Yoshikawa, Masayuki

    2009-10-15

    The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.

  2. Antifungal agents commonly used in the superficial and mucosal candidiasis treatment: mode of action and resistance development.

    Science.gov (United States)

    Bondaryk, Małgorzata; Kurzątkowski, Wiesław; Staniszewska, Monika

    2013-10-01

    Recent progress in medical sciences and therapy resulted in an increased number of immunocompromised individuals. Candida albicans is the leading opportunistic fungal pathogen causing infections in humans, ranging from superficial mucosal lesions to disseminated or bloodstream candidiasis. Superficial candidiasis not always presents a risk to the life of the infected host, however it significantly lowers the quality of life. Superficial Candida infections are difficult to treat and their frequency of occurrence is currently rising. To implement successful treatment doctors should be up to date with better understanding of C. albicans resistance mechanisms. Despite high frequency of Candida infections there is a limited number of antimycotics available for therapy. This review focuses on current understanding of the mode of action and resistance mechanisms to conventional and emerging antifungal agents for treatment of superficial and mucosal candidiasis.

  3. Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence.

    Science.gov (United States)

    Meek, M E Bette; Palermo, Christine M; Bachman, Ammie N; North, Colin M; Jeffrey Lewis, R

    2014-06-01

    The mode of action human relevance (MOA/HR) framework increases transparency in systematically considering data on MOA for end (adverse) effects and their relevance to humans. This framework continues to evolve as experience increases in its application. Though the MOA/HR framework is not designed to address the question of "how much information is enough" to support a hypothesized MOA in animals or its relevance to humans, its organizing construct has potential value in considering relative weight of evidence (WOE) among different cases and hypothesized MOA(s). This context is explored based on MOA analyses in published assessments to illustrate the relative extent of supporting data and their implications for dose-response analysis and involved comparisons for chemical assessments on trichloropropane, and carbon tetrachloride with several hypothesized MOA(s) for cancer. The WOE for each hypothesized MOA was summarized in narrative tables based on comparison and contrast of the extent and nature of the supporting database versus potentially inconsistent or missing information. The comparison was based on evolved Bradford Hill considerations rank ordered to reflect their relative contribution to WOE determinations of MOA taking into account increasing experience in their application internationally. This clarification of considerations for WOE determinations as a basis for comparative analysis is anticipated to contribute to increasing consistency in the application of MOA/HR analysis and potentially, transparency in separating science judgment from public policy considerations in regulatory risk assessment. Copyright © 2014. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

  4. The cytotoxicity of 1-(1-phenylalkylideneamino)-2,4-azetidinediones and their mode of action in human and murine tumor cells.

    Science.gov (United States)

    Izydore, R A; Zhang, Y; Zhou, X; Warren, A E; Wheaton, J R; Hall, I H

    2001-01-01

    The 1-(1-phenylalkylideneamino)-2,4-azetidinediones are potent cytotoxic agents against the growth of human and murine leukemias, lymphoma, and suspended HeLa uterine carcinoma. In cell lines cultured from solid human tumors, the agents were more selective with only a few agents demonstrating significant activity against the growth of HCT-8 ileum adenocarcinoma, Saos-2 osteosarcoma, KB nasopharynx, MCF-7 breast effusion, and ovary 1-A9 carcinoma A mode of action study in murine L1210 lymphoid leukemia cells showed that the agents inhibited DNA and RNA syntheses after 60 min. The compounds were potent inhibitors of the de novo purine synthesis suppressing the activity of both regulatory enzymes of the pathway, i.e., PRPP-amido transferase and IMP dehydrogenase. In addition, the agents reduced the activity of ribonucleotide reductase, dihydrofolate reductase, RNA polymerases, and thymidine kinases as well as the reduction of d[NTP] pools. All of these effects would contribute to the overall reduction of DNA and RNA syntheses. The DNA molecule itself was not a target for the agents in that alkylation of nucleoide bases, intercalation between base pairs, and cross-linking of DNA strands did not occur.

  5. MOAtox: A Comprehensive Mode of Action and Acute Aquatic Toxicity Database for Predictive Model Development

    Science.gov (United States)

    tThe mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity andas an alternative to chemical class-based predictive toxicity modeling. However, the development ofquantitative structure activity relationship (QSAR) and other models has been limite...

  6. Dissecting modes of action of non-genotoxic carcinogens in primary mouse hepatocytes.

    NARCIS (Netherlands)

    Schaap, M.M.; Zwart, E.P.; Wackers, P.F.K.; Huijskens, I.; van de Water, B.; Breit, T.M.; van Steeg, H.; Jonker, M.J.; Luijten, M.

    2012-01-01

    Under REACH, the European Community Regulation on chemicals, the testing strategy for carcinogenicity is based on in vitro and in vivo genotoxicity assays. Given that non-genotoxic carcinogens are negative for genotoxicity and chronic bioassays are no longer regularly performed, this class of

  7. Catalytic Mechanism and Mode of Action of the Periplasmic Alginate Epimerase AlgG

    NARCIS (Netherlands)

    Wolfram, Francis; Kitova, Elena N.; Robinson, Howard; Walvoort, Marthe T. C.; Codee, Jeroen D. C.; Klassen, John S.; Howell, P. Lynne

    2014-01-01

    Background: The alginate epimerase AlgG converts mannuronate to its C5 epimer guluronate at the polymer level. Results: The structure of Pseudomonas syringae AlgG has been determined, and the protein has been functionally characterized. Conclusion: His(319) acts as the catalytic base, whereas

  8. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: An Evaluation of approaches

    Science.gov (United States)

    The mode of toxic action (MOA) is recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, MOA classification has never been standardized in ecotoxicology, and a comprehensive comparison of classific...

  9. [Metamizole (dipyrone): mode of action, drug-drug interactions, and risk of agranulocytosis].

    Science.gov (United States)

    Lampl, C; Likar, R

    2014-12-01

    Metamizole (dipyrone) is a nonsteroidal compound with strong analgesic as well as antipyretic and spasmolytic properties. Based on a small number of cases of agranulocytosis, metamizole was withdrawn from the market in some countries. Other countries restricted its use. This paper discusses the safety aspects of metamizole and compares it with other compounds used for similar indications.

  10. A Mini HIP HOP Assay Uncovers a Central Role for Copper and Zinc in the Antifungal Mode of Action of Allicin.

    Science.gov (United States)

    Prescott, Thomas A K; Panaretou, Barry

    2017-05-10

    Garlic contains the organosulfur compound allicin which exhibits potent antifungal activity. Here we demonstrate the use of a highly simplified yeast chemical genetic screen to characterize its mode of action. By screening 24 validated yeast gene deletion "signature" strains for which hypersensitivity is characteristic for common antifungal modes of action, yeast lacking the high affinity Cu 2+ transporter Ctr1 was found to be hypersensitive to allicin. Focusing on transition metal related genes identified two more hypersensitive strains lacking the Cu 2+ and Zn 2+ transcription factors Mac1 and Zap1. Hypersensitivity in these strains was reversed by the addition of Cu 2+ and Zn 2+ ions, respectively. The results suggest the antifungal activity of allicin is mediated through restricted Cu 2+ and Zn 2+ uptake or inhibition of Cu 2+ and Zn 2+ metalloproteins. As certain antimicrobial modes of action are much more common than others, the approach taken here provides a useful way to identify them early on.

  11. Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A

    Science.gov (United States)

    1989-07-15

    phospholipids preradiolabeled by feeding the cells 1.4C-fatty acids overnight. To develop potential prophylactic and therapeutic agents, pharmacological studies...PLAz neurotoxins. Experimental Methods: Materials. Vencm from 1 nAjA atra, CTX from Naja n9ja kaouthia venom (Lots 125F-4007), bee venom PLAz ( Apis ... mellifera ), melittin, B-bungarotoxin, Tris base, Hepes (4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid), Mes (4- morpholineethanesulfonic acid), bovine

  12. Specificity determinants for Cry insecticidal proteins: insights from their mode of action

    OpenAIRE

    Jurat-Fuentes, Juan Luis; Crickmore, Neil

    2017-01-01

    Insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) are used as active components of biopesticides and as plant incorporated protectants in transgenic crops. One of the most relevant attributes of these Bt protein-based insecticidal technologies is their high specificity, which assures lack of detrimental effects on non-target insects, vertebrates and the environment. The identification of specificity determinants in Bt insecticidal proteins could guide risk assessment for no...

  13. Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths.

    Science.gov (United States)

    Palli, S R; Tice, C M; Margam, V M; Clark, A M

    2005-04-01

    THQ (1-aroyl-4-(arylamino)-1,2,3,4-tetrahydroquinoline) compounds were identified by FMC Corporation in cell-based assays that used ecdysone receptors from Drosophila melanogaster, Heliothis virescens, or Plodia interpunctata. THQ compounds showed weak insecticidal activity against H. virescens and, therefore, were not developed further. Several ecdysone agonists based on THQ chemotype have been synthesized and tested for their activity against a number of EcRs in transactivation assays. The THQ compound, RG-120768, activated AaEcR (EcR from A. aegypti) but did not activate EcRs cloned from other insects. In transactivation assays, all six THQ ligands tested functioned through AaEcR but not through CfEcR (EcR from Choristoneura fumiferana). Three THQ compounds that showed higher activity in transactivation assays were tested in tobacco bud moth, H. virescens, and yellow fever mosquito, A. aegypti. These compounds showed higher activity in A. aegypti when compared to their activity in H. virescens. These data show that the THQ ligands are a new class of non-steroidal ecdysone agonists with preferential activity against mosquitoes. Copyright 2005 Wiley-Liss, Inc.

  14. QSAR analysis of nitroaromatics' toxicity in Tetrahymena pyriformis: structural factors and possible modes of action

    Science.gov (United States)

    Artemenko, A.G.; Muratov, E. N.; Kuz’min, V.E.; Muratov, N.N.; Varlamova, E.V.; Kuz'mina, A.V.; Gorb, L. G.; Golius, A.; Hill, F.C.; Leszczynski, J.; Tropsha, A.

    2012-01-01

    The Hierarchical Technology for Quantitative Structure - Activity Relationships (HiT QSAR) was applied to 95 diverse nitroaromatic compounds (including some widely known explosives) tested for their toxicity (50% inhibition growth concentration, IGC50) against the ciliate Tetrahymena pyriformis. The dataset was divided into subsets according to putative mechanisms of toxicity. Classification and Regression Trees (CART) approach implemented within HiT QSAR has been used for prediction of mechanism of toxicity for new compounds. The resulting models were shown to have ~80% accuracy for external datasets indicating that the mechanistic dataset division was sensible. Then, Partial Least Squares (PLS) statistical approach was used for the development of 2D QSAR models. Validated PLS models were explored to (i) elucidate the effects of different substituents in nitroaromatic compounds on toxicity; (ii) differentiate compounds by probable mechanisms of toxicity based on their structural descriptors; (iii) analyze the role of various physical-chemical factors responsible for compounds’ toxicity. Models were interpreted in terms of molecular fragments promoting or interfering with toxicity. It was also shown that mutual influence of substituents in benzene ring plays the determining role in toxicity variation. Although chemical mechanism based models were statistically significant and externally predictive (R2ext=0.64 for the external set of 63 nitroaromatics identified after all calculations have been completed), they were also shown to have limited coverage (57% for modeling and 76% for external set). PMID:21714735

  15. Application of the U.S. EPA Mode of Action Framework for Purposes of Guiding Future Research: A Case Study Involving the Oral Carcinogenicity of Hexavalent Chromium

    Science.gov (United States)

    Thompson, Chad M.; Haws, Laurie C.; Harris, Mark A.; Gatto, Nicole M.; Proctor, Deborah M.

    2011-01-01

    Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment. PMID:20947717

  16. Mode of action of dioxin-like versus non-dioxin-like PCBs

    Energy Technology Data Exchange (ETDEWEB)

    Schoeters, G. [VITO (Flemish Institute for Technological Research), Dept. of Environemental Toxicology (Belgium)]|[Antwerp Univ. (Belgium); Birnbaum, L. [United States Environmental Protection Agency, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory (United States)

    2004-09-15

    Exposure of humans to polychlorinated biphenyls has been associated with different adverse effects such as immune impairment, changes in hormone levels, reproductive and neuropsychological changes and cancer. It is difficult to attribute the observed effects to either dioxin-like, non-dioxin-like PCBs or to both. All known human exposures are mixed, comprising dioxin and non-dioxin like PCB congeners as well as dioxins and furans. The purpose of this work was to evaluate, based on mechanistic data available in the open literature, whether non-dioxin like PCBs (NDL-PCBs) themselves may pose specific health risks. It is clear that dioxin and NDL-PCBs differ in the spectrum of metabolizing enzymes they induce, but the mechanistic links to health of these biochemical changes remain unclear at the moment. NDL-PCBs also cause immunotoxicity and tumor promotion via different mechanisms than do dioxin-like PCBs. We focus on neurotoxicity which has been associated with developmental exposure to PCBs and which is considered as one of the most sensitive adverse health effects.

  17. Lithium chloride effectively kills the honey bee parasite Varroa destructor by a systemic mode of action.

    Science.gov (United States)

    Ziegelmann, Bettina; Abele, Elisabeth; Hannus, Stefan; Beitzinger, Michaela; Berg, Stefan; Rosenkranz, Peter

    2018-01-12

    Honey bees are increasingly important in the pollination of crops and wild plants. Recent reports of the weakening and periodical high losses of managed honey bee colonies have alarmed beekeeper, farmers and scientists. Infestations with the ectoparasitic mite Varroa destructor in combination with its associated viruses have been identified as a crucial driver of these health problems. Although yearly treatments are required to prevent collapses of honey bee colonies, the number of effective acaricides is small and no new active compounds have been registered in the past 25 years. RNAi-based methods were proposed recently as a promising new tool. However, the application of these methods according to published protocols has led to a surprising discovery. Here, we show that the lithium chloride that was used to precipitate RNA and other lithium compounds is highly effective at killing Varroa mites when fed to host bees at low millimolar concentrations. Experiments with caged bees and brood-free artificial swarms consisting of a queen and several thousand bees clearly demonstrate the potential of lithium as miticidal agent with good tolerability in worker bees providing a promising basis for the development of an effective and easy-to-apply control method for mite treatment.

  18. The history, chemistry and modes of action of carmine and related dyes.

    Science.gov (United States)

    Dapson, R W

    2007-08-01

    by heating. Each of the major classes of carmine-based stains is described as are possible mechanisms of attachment to specific substrates. Glycogen binds carmine through hydrogen bonding, and it is here that carmine decomposed by heat could have the greatest detrimental impact. Nuclei and chromosomes are stained via coordination bonds, perhaps supplemented by hydrogen bonds. Finally, acidic mucins react ionically with carmine. Specificity in the latter case may be due to unique polymeric carmine molecules that form in the presence of aluminum chloride.

  19. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  20. Mode of Action and Specificity of Bacillus thuringiensis Toxins in the Control of Caterpillars and Stink Bugs in Soybean Culture

    Science.gov (United States)

    Fiuza, Lidia Mariana

    2014-01-01

    The bacterium Bacillus thuringiensis (Bt) produces delta-endotoxins that possess toxic properties and can be used as biopesticides, as well as a source of genes for the construction of transgenic plants resistant to insects. In Brazil, the introduction of Bt soybean with insecticidal properties to the velvetbean caterpillar, the main insect pest of soybean, has been seen a promising tool in the management of these agroecosystems. However, the increase in stink bug populations in this culture, in various regions of the country, which are not susceptible to the existing genetically modified plants, requires application of chemicals that damage the environment. Little is known about the actual toxicity of Bt to Hemiptera, since these insects present sucking mouthparts, which hamper toxicity assays with artificial diets containing toxins of this bacterium. In recent studies of cytotoxicity with the gut of different hemipterans, susceptibility in the mechanism of action of delta-endotoxins has been demonstrated, which can generate promising subsidies for the control of these insect pests in soybean. This paper aims to review the studies related to the selection, application and mode of action of Bt in the biological control of the major pest of soybean, Anticarsia gemmatalis, and an analysis of advances in research on the use of Bt for control hemipterans. PMID:24575310

  1. Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action.

    Directory of Open Access Journals (Sweden)

    Chang Ji Zheng

    Full Text Available Bacterial enoyl-acyl carrier protein reductase (FabI is a promising novel antibacterial target. We isolated a new class of FabI inhibitor from Penicillium chrysogenum, which produces various antibiotics, the mechanisms of some of them are unknown. The isolated FabI inhibitor was determined to be meleagrin by mass spectroscopy and nuclear magnetic resonance spectral analyses, and its more active and inactive derivatives were chemically prepared. Consistent with their selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active derivatives directly bound to S. aureus FabI in a fluorescence quenching assay, inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and increased the minimum inhibitory concentration for fabI-overexpressing S. aureus. The compounds that were not effective against the FabK isoform, however, inhibited the growth of Streptococcus pneumoniae that contained only the FabK isoform. Additionally no resistant mutant to the compounds was obtained. Importantly, fabK-overexpressing Escherichia coli was not resistant to these compounds, but was resistant to triclosan. These results demonstrate that the compounds inhibited another target in addition to FabI. Thus, meleagrin is a new class of FabI inhibitor with at least one additional mode of action that could have potential for treating multidrug-resistant bacteria.

  2. Mode of action of cupping--local metabolism and pain thresholds in neck pain patients and healthy subjects.

    Science.gov (United States)

    Emerich, M; Braeunig, M; Clement, H W; Lüdtke, R; Huber, R

    2014-02-01

    Cupping worldwide has been part of traditional medicine systems and is in the western world used as CAM therapy mainly for treating pain syndromes. The mode of action is up to now unclear. In order to investigate its mechanism we measured in parallel metabolic changes in the tissue under the cupping glass and pressure pain thresholds. In 12 volunteers (6 healthy subjects and 6 patients with chronic neck pain) a microdialysis system was implanted subcutaneously on both sides (left and right) above the trapezius muscle. After baseline measures cupping was performed at one randomly selected side (left or right), the other side served as control. Every 20 min during baseline measures and for 280 min after cupping, microdialysis probes for detection of lactate, pyruvate, glucose and glycerin were taken. In addition, pain thresholds were measured before and after cupping with algometry. Cupping resulted in a strong increase of lactate (beginning 160 min after cupping until the end of the measurements) and the lactate/pyruvate ratio, indicating an anaerobe metabolism in the surrounding tissue. Baseline pain thresholds were non-significantly lower in neck pain patients compared to healthy controls and slightly increased immediately after cupping (pcupping in healthy subjects and on the foot in neck pain patients). After 280 min no more significant changes of pain thresholds were detected. Cupping induces >280 min lasting anaerobe metabolism in the subcutaneous tissue and increases immediate pressure pain thresholds in some areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Classifying chemical mode of action using gene networks and machine learning: a case study with the herbicide linuron.

    Science.gov (United States)

    Ornostay, Anna; Cowie, Andrew M; Hindle, Matthew; Baker, Christopher J O; Martyniuk, Christopher J

    2013-12-01

    The herbicide linuron (LIN) is an endocrine disruptor with an anti-androgenic mode of action. The objectives of this study were to (1) improve knowledge of androgen and anti-androgen signaling in the teleostean ovary and to (2) assess the ability of gene networks and machine learning to classify LIN as an anti-androgen using transcriptomic data. Ovarian explants from vitellogenic fathead minnows (FHMs) were exposed to three concentrations of either 5α-dihydrotestosterone (DHT), flutamide (FLUT), or LIN for 12h. Ovaries exposed to DHT showed a significant increase in 17β-estradiol (E2) production while FLUT and LIN had no effect on E2. To improve understanding of androgen receptor signaling in the ovary, a reciprocal gene expression network was constructed for DHT and FLUT using pathway analysis and these data suggested that steroid metabolism, translation, and DNA replication are processes regulated through AR signaling in the ovary. Sub-network enrichment analysis revealed that FLUT and LIN shared more regulated gene networks in common compared to DHT. Using transcriptomic datasets from different fish species, machine learning algorithms classified LIN successfully with other anti-androgens. This study advances knowledge regarding molecular signaling cascades in the ovary that are responsive to androgens and anti-androgens and provides proof of concept that gene network analysis and machine learning can classify priority chemicals using experimental transcriptomic data collected from different fish species. © 2013.

  4. Combined effect of enterocin and lipase from Enterococcus faecium NCIM5363 against food borne pathogens: mode of action studies.

    Science.gov (United States)

    Ramakrishnan, Vrinda; Narayan, Bhaskar; Halami, Prakash M

    2012-08-01

    Food borne diseases have a major impact on public health whose epidemiology is rapidly changing. The whole cells of pathogens involved or their toxins/metabolites affect the human health apart from spoiling sensory properties of the food products finally affecting the food industry as well as consumer health. With pathogens developing mechanisms of antibiotic resistance, there has been an increased need to replace antibiotics as well as chemical additives with naturally occurring bacteriocins. Bacteriocins are known to act mainly against Gram-positive pathogens and with little or no effect towards Gram-negative enteric bacteria. In the present study, combination effect of lipase and bacteriocin produced by Enterococcus faecium NCIM5363, a highly lipolytic lactic acid bacterium against various food pathogens was assessed. The lipase in combination with enterocin exhibited a lethal effect against Gram-negative pathogens. Scanning electron microscopy studies carried out to ascertain the constitutive mode of action of lipase and enterocin revealed that the lipase degrades the cell wall of Gram-negative bacteria and creates a pore through which enterocin enters thereby resulting in cell death. The novelty of this work is the fact that this is the first report revealing the synergistic effect of lipase with enterocin against Gram-negative bacteria.

  5. Cyanobacterial toxins: modes of actions, fate in aquatic and soil ecosystems, phytotoxicity and bioaccumulation in agricultural crops.

    Science.gov (United States)

    Corbel, Sylvain; Mougin, Christian; Bouaïcha, Noureddine

    2014-02-01

    The occurrence of harmful cyanobacterial blooms in surface waters is often accompanied by the production of a variety of cyanotoxins. These toxins are designed to target in humans and animals specific organs on which they act: hepatotoxins (liver), neurotoxins (nervous system), cytotoxic alkaloids, and dermatotoxins (skin), but they often have important side effects too. When introduced into the soil ecosystem by spray irrigation of crops they may affect the same molecular pathways in plants having identical or similar target organs, tissues, cells or biomolecules. There are also several indications that terrestrial plants, including food crop plants, can bioaccumulate cyanotoxins and present, therefore, potential health hazards for human and animals. The number of publications concerned with phytotoxic effects of cyanotoxins on agricultural plants has increased recently. In this review, we first examine different cyanotoxins and their modes of actions in humans and mammals and occurrence of target biomolecules in vegetable organisms. Then we present environmental concentrations of cyanotoxins in freshwaters and their fate in aquatic and soil ecosystems. Finally, we highlight bioaccumulation of cyanotoxins in plants used for feed and food and its consequences on animals and human health. Overall, our review shows that the information on the effects of cyanotoxins on non-target organisms in the terrestrial environment is particularly scarce, and that there are still serious gaps in the knowledge about the fate in the soil ecosystems and phytotoxicity of these toxins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Biological approaches to characterize the mode of action of two 5-nitroindazolinone prototypes on Trypanosoma cruzi bloodstream trypomastigotes.

    Science.gov (United States)

    Fonseca-Berzal, Cristina; DA Silva, Cristiane França; Menna-Barreto, Rubem F S; Batista, Marcos Meuser; Escario, José A; Arán, Vicente J; Gómez-Barrio, Alicia; Soeiro, Maria DE Nazaré C

    2016-09-01

    The phenotypic activity of two 5-nitroindazolinones, i.e. 2-benzyl-1-propyl (22) and 2-benzyl-1-butyl (24) derivatives, previously proposed as anti-Trypanosoma cruzi prototypes, was presently assayed on bloodstream trypomastigotes (BT) of the moderately drug-resistant Y strain. Further exploration of putative targets and cellular mechanisms involved in their activity was also carried out. Therefore, transmission electron microscopy, high-resolution respirometry and flow cytometry procedures were performed on BT treated for up to 24 h with the respective EC50 value of each derivative. Results demonstrated that although 22 and 24 were not as active as benznidazole in this in vitro assay on BT, both compounds triggered important damages in T. cruzi that lead to the parasite death. Ultrastructural alterations included shedding events, detachment of plasma membrane and nuclear envelope, loss of mitochondrial integrity, besides the occurrence of a large number of intracellular vesicles and profiles of endoplasmic reticulum surrounding cytoplasmic organelles such as mitochondrion. Moreover, both derivatives affected mitochondrion leading to this organelle dysfunction, as reflected by the inhibition in oxygen consumption and the loss of mitochondrial membrane potential. Altogether, the findings exposed in the present study propose autophagic processes and mitochondrial machinery as part of the mode of action of both 5-nitroindazolinones 22 and 24 on T. cruzi trypomastigotes.

  7. Efficacy of Combined Formulations of Fungicides with Different Modes of Action in Controlling Botrytis Gray Mold Disease in Chickpea

    Directory of Open Access Journals (Sweden)

    M. H. Rashid

    2014-01-01

    Full Text Available Botrytis gray mold (BGM caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L. and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur in Bangladesh for three years (2008, 2009, and 2010. Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%, and Protaf 250EC, propiconazole (0.05%], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%; Secure 600 WG, phenomadone + mancozeb (0.2%; and Companion, mancozeb 63% + carbendazim 12% (0.2%]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale and the highest increase (38% of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

  8. Developing Pantetheinase-Resistant Pantothenamide Antibacterials: Structural Modification Impacts on PanK Interaction and Mode of Action.

    Science.gov (United States)

    Barnard, Leanne; Mostert, Konrad J; van Otterlo, Willem A L; Strauss, Erick

    2018-01-23

    Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic precursor of coenzyme A (CoA), and show potent antimicrobial activity against several bacteria and the malaria parasite in vitro. However, pantetheinase enzymes that normally degrade pantetheine in human serum also act on the PanAms, thereby reducing their potency. In this study, we designed analogues of the known antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to pantetheinase by using three complementary structural modification strategies. We show that, while two of these are effective in imparting resistance, the introduced modifications have an impact on the analogues' interaction with pantothenate kinase (PanK, the first CoA biosynthetic enzyme), which acts as a metabolic activator and/or target of the PanAms. This, in turn, directly affects their mode of action. Importantly, we discover that the phosphorylated version of N7-Pan shows pantetheinase resistance and antistaphylococcal activity, providing a lead for future studies in the ongoing search of PanAm analogues that show in vivo efficacy.

  9. Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.

    Science.gov (United States)

    Ramirez, Tzutzuy; Strigun, Alexander; Verlohner, Andreas; Huener, Hans-Albrecht; Peter, Erik; Herold, Michael; Bordag, Natalie; Mellert, Werner; Walk, Tilmann; Spitzer, Michael; Jiang, Xiaoqi; Sperber, Saskia; Hofmann, Thomas; Hartung, Thomas; Kamp, Hennicke; van Ravenzwaay, Ben

    2017-09-30

    Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions. Here, we combined mass-spectroscopy metabolomics with an in vitro liver toxicity model. Metabolite profiles of HepG2 cells treated with 35 test substances resulted in 1114 cell supernatants and 3556 intracellular samples analyzed by metabolomics. Control samples showed relative standard deviations of about 10-15%, while the technical replicates were at 5-10%. Importantly, this procedure revealed concentration-response effects and patterns of metabolome changes that are consistent for different liver toxicity mechanisms (liver enzyme induction/inhibition, liver toxicity and peroxisome proliferation). Our findings provide evidence that identifying organ toxicity can be achieved in a robust, reliable, human-relevant system, representing a non-animal alternative for systemic toxicology.

  10. Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria

    NARCIS (Netherlands)

    Omardien, S.; Brul, S.; Zaat, S.A.J.

    2016-01-01

    Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the

  11. Use of Electroencephalography (EEG) to Assess CNS Changes Produced by Pesticides with different Modes of Action: Effects of Permethrin, Deltamethrin, Fipronil, Imidacloprid, Carbaryl, and Triadimefon

    Science.gov (United States)

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long-Evans rats...

  12. Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action

    Science.gov (United States)

    This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

  13. Meta-Analysis of Fish Early Life Stage Tests - Association of Toxic Ratios and Acute-To-Chronic Ratios with Modes of Action

    DEFF Research Database (Denmark)

    Scholz, Stefan; Schreiber, Rene; Armitage, James

    2018-01-01

    Fish early life stage (FELS) tests (OECD test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stage. In order to analyse whether certain modes of action are related to high toxic ratios (TR, i.e., rati...

  14. Developing Toxicogenomics as a Research Tool by Applying Benchmark Dose-Response Modeling to inform Chemical Mode of Action and Tumorigenic Potency

    Science.gov (United States)

    ABSTRACT Results of global gene expression profiling after short-term exposures can be used to inform tumorigenic potency and chemical mode of action (MOA) and thus serve as a strategy to prioritize future or data-poor chemicals for further evaluation. This compilation of cas...

  15. PROCEEDINGS OF THE 2008 Computers in Music Modeling and Retrieval and Network for Cross-Disciplinary Studies of Music and Meaning Conference

    DEFF Research Database (Denmark)

    and encouraged studies that linked sound modeling by analysis-synthesis to perception and cognition. CMMR 2008 seeks to enlarge upon the Sense of Sounds-concept by taking into account the musical structure as a whole. More precisely, the workshop will have as its theme Genesis of Meaning in Sound and Music...... of sound meaning and its implications in music, modelling and retrieval. as a step in this direction, NTSMb, the Network for Cross-Disciplinary Studies of Music and Meaning (www.ntsmb.dk) and JMM: The Journal of Music and Meaning (www.musicandmeaning.net will be joining as participants in CMMR 2008. CMMR...... the symposium as a post-event proceedings in the Springer verlag Lecture Notes in Computer Science (LNCS) Series is planned. an award for the best paper dealing with the theme of the conference - Genesis of Meaning in Sound and Music - will be given under the auspices of The Journal of Music and Meaning....

  16. The Mode of Action of Isocyanide in Three Aquatic Organisms, Balanus amphitrite, Bugula neritina and Danio rerio

    KAUST Repository

    Zhang, Yi-Fan

    2012-09-18

    Isocyanide is a potential antifouling compound in marine environments. In this study, we investigated its mode of action in three aquatic organisms. Two of them, the bryozoan Bugula neritina and the barnacle Balanus amphitrite, are major marine fouling invertebrates, and the other organism is the non-target species zebrafish Danio rerio. In the swimming larvae of B. neritina, isocyanide did not affect the total attachment rate (≤50 µg ml^(−1)), but it did change the attachment site by increasing the percentage of attachment on the bottom of the container rather than on the wall or air-water inter-surface. Isocyanide binds several proteins in B. neritina as identified via SDS-PAGE-LC-MS/MS: 1) a 30 kD protein band containing two proteins similar to voltage dependent anion channels (VDAC), which control the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol and the release of apoptogenic factors from mitochondria of mammalian cells; and 2) an unknown 39 kD protein. In B. amphitrite cyprids, the isocyanide binding protein were 1) a protein similar to NADH-ubiquinone oxidoreductase, which is the “entry enzyme” of oxidative phosphorylation in mitochondria; and 2) cytochrome P450. In Danio rerio embryos, isocyanide caused “wavy” notochords, hydrocephalus, pericardial edema, poor blood circulation, and defects in pigmentation and hematopoiesis, which phenocopied copper deficiency. This is the first report on isocyanide binding proteins in fouling organisms, as well as the first description of its phenotype and potential toxicology in zebrafish.

  17. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

    Directory of Open Access Journals (Sweden)

    Amrita Banerjee

    2014-01-01

    Full Text Available Mithramycin (MTR is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode or both histones and chromosomal DNA (dual binding mode. The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

  18. On the mode of action of emodepside: slow effects on membrane potential and voltage-activated currents in Ascaris suum

    Science.gov (United States)

    Buxton, SK; Neveu, C; Charvet, CL; Robertson, AP; Martin, RJ

    2011-01-01

    BACKGROUND AND PURPOSE Anthelmintics are required for treatment and prophylaxis of nematode parasites of humans and domestic animals. Emodepside, a cyclooctadepsipeptide, is a modern anthelmintic that has a novel mode of action involving a Ca-activated K channel (SLO-1) in Caenorhabditis elegans, sometimes mediated by a latrophilin (LAT) receptor. We examined mechanisms of action of emodepside in a parasitic nematode, Ascaris suum. EXPERIMENTAL APPROACH RT-PCR was used to investigate expression of slo-1 and lat-1 in A. suum muscle flaps, and two-micropipette current-clamp and voltage-clamp techniques were used to record electrophysiological effects of emodepside. KEY RESULTS Expression of slo-1 and lat-1 were detected. Emodepside produced a slow time-dependent (20 min), 4-aminopyridine sensitive, concentration-dependent hyperpolarization and increase in voltage-activated K currents. Sodium nitroprusside increased the hyperpolarizations and K currents. N-nitro-L-arginine inhibited the hyperpolarizations and K currents. Phorbol-12-myristate-13 acetate increased the K currents, while staurosporine inhibited the hyperpolarizations and K currents. Iberiotoxin reduced these emodepside K currents. The effect of emodepside was reduced in Ca-free solutions. Emodepside had no effect on voltage-activated Ca currents. CONCLUSIONS AND IMPLICATIONS Asu-slo-1 and Asu-lat-1 are expressed in adult A. suum muscle flaps and emodepside produces slow activation of voltage-activated Ca-dependent SLO-1-like K channels. The effect of emodepside was enhanced by stimulation of protein kinase C and NO pathways. The data are consistent with a model in which NO, PKC and emodepside signalling pathways are separate and converge on the K channels, or in which emodepside activates NO and PKC signalling pathways to increase opening of the K channels. PMID:21486286

  19. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action

    Science.gov (United States)

    Vijayakumar, Paul Priyesh; Muriana, Peter M.

    2015-01-01

    Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes. PMID:26111195

  20. Vasorelaxant mode of action of dichloromethane-soluble extract from Agastache mexicana and its main bioactive compounds.

    Science.gov (United States)

    Flores-Flores, Angélica; Hernández-Abreu, Oswaldo; Rios, María Yolanda; León-Rivera, Ismael; Aguilar-Guadarrama, Berenice; Castillo-España, Patricia; Perea-Arango, Irene; Estrada-Soto, Samuel

    2016-12-01

    Agastache mexicana (Kunth) Lint & Epling (Lamiaceae) is a plant used in Mexican traditional medicine for the treatment of hypertension, anxiety and so on. To determine the vasorelaxant effect and functional mode of action of dichloromethane-soluble extract from A. mexicana (DEAm) and isolate the constituents responsible for the pharmacological activity. Extracts were prepared from the aerial parts of A. mexicana (225.6 g) by successive maceration with hexane, dichloromethane and methanol (three times for 72 h at room temperature), respectively. DEAm (0.01-1000 μg/mL), fractions (at 174.27 μg/mL), acacetin and ursolic acid (UA) (0.5-500 μM) were evaluated to determine their vasorelaxant effect on ex vivo rat aorta ring model. In vivo UA antihypertensive action was determined on spontaneously hypertensive rats. DEAm induced a significant vasorelaxant effect in concentration-dependent and endothelium-independent manners (EC 50  =   174.276 ± 5.98 μg/mL) by a calcium channel blockade and potassium channel opening. Bio-guided fractionation allowed to isolate acacetin (112 mg), UA (2.830 g), acacetin/oleanolic acid (OA) (M1) (155 mg) and acacetin/OA/UA (M2) (1.382 g) mixtures, which also showed significant vasodilation. UA significantly diminished diastolic (80 mmHg) and systolic blood pressure (120 mmHg), but heart rate was not modified. DEAm produced significant vasorelaxant action by myogenic control cation. The presence of acacetin, OA and UA into the extract was substantial for the relaxant activity of DEAm. In vivo antihypertensive action of UA corroborates the use of A. mexicana as an antihypertensive agent on Mexican folk medicine.

  1. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action

    Directory of Open Access Journals (Sweden)

    Paul Priyesh Vijayakumar

    2015-06-01

    Full Text Available Lactic acid bacteria (LAB have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes.

  2. Antifungal activity, mode of action and anti-biofilm effects of Laurus nobilis Linnaeus essential oil against Candida spp.

    Science.gov (United States)

    Peixoto, Larissa Rangel; Rosalen, Pedro Luiz; Ferreira, Gabriela Lacet Silva; Freires, Irlan Almeida; de Carvalho, Fabíola Galbiatti; Castellano, Lúcio Roberto; de Castro, Ricardo Dias

    2017-01-01

    The present study demonstrated the antifungal potential of the chemically characterized essential oil (EO) of Laurus nobilis L. (bay laurel) against Candida spp. biofilm adhesion and formation, and further established its mode of action on C. albicans. L. nobilis EO was obtained and tested for its minimum inhibitory and fungicidal concentrations (MIC/MFC) against Candida spp., as well as for interaction with cell wall biosynthesis and membrane ionic permeability. Then we evaluated its effects on the adhesion, formation, and reduction of 48hC. albicans biofilms. The EO phytochemical profile was determined by gas chromatography coupled to mass spectrometry (GC/MS). The MIC and MFC values of the EO ranged from (250 to 500) μg/mL. The MIC values increased in the presence of sorbitol (osmotic protector) and ergosterol, which indicates that the EO may affect cell wall biosynthesis and membrane ionic permeability, respectively. At 2 MIC the EO disrupted initial adhesion of C. albicans biofilms (p0.05). When applied for 1min, every 8h, for 24h and 48h, the EO reduced the amount of C. albicans mature biofilm with no difference in relation to nystatin (p>0.05). The phytochemical analysis identified isoeugenol as the major compound (53.49%) in the sample. L. nobilis EO has antifungal activity probably due to monoterpenes and sesquiterpenes in its composition. This EO may affect cell wall biosynthesis and membrane permeability, and showed deleterious effects against C. albicans biofilms. Copyright © 2016. Published by Elsevier Ltd.

  3. Toward Understanding the Cold, Hot, and Neutral Nature of Chinese Medicines Using in Silico Mode-of-Action Analysis.

    Science.gov (United States)

    Fu, Xianjun; Mervin, Lewis H; Li, Xuebo; Yu, Huayun; Li, Jiaoyang; Mohamad Zobir, Siti Zuraidah; Zoufir, Azedine; Zhou, Yang; Song, Yongmei; Wang, Zhenguo; Bender, Andreas

    2017-03-27

    One important, however, poorly understood, concept of Traditional Chinese Medicine (TCM) is that of hot, cold, and neutral nature of its bioactive principles. To advance the field, in this study, we analyzed compound-nature pairs from TCM on a large scale (>23 000 structures) via chemical space visualizations to understand its physicochemical domain and in silico target prediction to understand differences related to their modes-of-action (MoA) against proteins. We found that overall TCM natures spread into different subclusters with specific molecular patterns, as opposed to forming coherent global groups. Compounds associated with cold nature had a lower clogP and contain more aliphatic rings than the other groups and were found to control detoxification, heat-clearing, heart development processes, and have sedative function, associated with "Mental and behavioural disorders" diseases. While compounds associated with hot nature were on average of lower molecular weight, have more aromatic ring systems than other groups, frequently seemed to control body temperature, have cardio-protection function, improve fertility and sexual function, and represent excitatory or activating effects, associated with "endocrine, nutritional and metabolic diseases" and "diseases of the circulatory system". Compounds associated with neutral nature had a higher polar surface area and contain more cyclohexene moieties than other groups and seem to be related to memory function, suggesting that their nature may be a useful guide for their utility in neural degenerative diseases. We were hence able to elucidate the difference between different nature classes in TCM on the molecular level, and on a large data set, for the first time, thereby helping a better understanding of TCM nature theory and bridging the gap between traditional medicine and our current understanding of the human body.

  4. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    Science.gov (United States)

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment. Copyright © 2016 The Authors. Published by

  5. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

    Directory of Open Access Journals (Sweden)

    Alison M Anderson

    Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

  6. Cardiac disorders and mode of action of the Egyptian scorpion venom Androctonus bicolor on isolated toad’s heart

    Directory of Open Access Journals (Sweden)

    Mohamed A. Abdel-Rahman

    2015-10-01

    Full Text Available Scorpion venom is a complex mixture of components with various pharmacological and toxicological effects. It is characterized by the presence of a large number of toxins that specifically interact with ion channels of excitable cells. The Egyptian scorpion Androctonus bicolor belongs to the family of Buthidae and until now no information is available about the effect of its venom on cardiac muscles. Using an in vitro approach, cardiotoxicity and mode of action of A. bicolor venom on isolated toad’s heart were investigated. Direct application of scorpion venom (0.5 μg/ml into isolated toad’s heart induced a remarkable bradycardia concomitant with a protraction in the conduction time (P–R interval. In the meantime, a significant increase in the R-wave amplitude (ventricular contraction was noticed after 5 min of venom perfusion. Various cases of cardiac disorders were recorded such as sinus arrhythmias, ectopic beats and different degrees of heart block. Through using different autonomic and ion channel blockers, the possible mechanism of action of A. bicolor venom on isolated toad’s heart was revealed. The application of both atropine (4 μg/ml and verapamil (5 μg/ml could not alleviate the pronounced negative chronotropic and positive inotropic effects. Meanwhile, a significant decrease in the R-wave amplitude was observed after propranolol (5 μg/ml application. In conclusion, our findings indicate that the venom of A. bicolor directly influenced the cardiac electrical activity of toads through β-adrenergic receptors. The direct effect of this venom on cardiac tissues may significantly contribute in the development of several cardiotoxic effects following scorpion sting.

  7. Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi: is oxidative stress involved?

    Science.gov (United States)

    Boiani, Mariana; Piacenza, Lucia; Hernández, Paola; Boiani, Lucia; Cerecetto, Hugo; González, Mercedes; Denicola, Ana

    2010-06-15

    Chagas disease is caused by the trypanosomatid parasite Trypanosoma cruzi and threatens millions of lives in South America. As other neglected diseases there is almost no research and development effort by the pharmaceutical industry and the treatment relies on two drugs, Nifurtimox and Benznidazole, discovered empirically more than three decades ago. Nifurtimox, a nitrofurane derivative, is believed to exert its biological activity through the bioreduction of the nitro-group to a nitro-anion radical which undergoes redox-cycling with molecular oxygen. This hypothesis is generally accepted, although arguments against it have been presented. In the present work we studied the ability of Nifurtimox and five N-oxide-containing heterocycles to induce oxidative stress in T. cruzi. N-Oxide-containing heterocycles represent a promising group of new trypanosomicidal agents and their mode of action is not completely elucidated. The results here obtained argue against the oxidative stress hypothesis almost for all the studied compounds, including Nifurtimox. A significant reduction in the level of parasitic low-molecular-weight thiols was observed after Nifurtimox treatment; however, it was not linked to the production of reactive oxidant species. Besides, redox-cycling is only observed at high Nifurtimox concentrations (>400microM), two orders of magnitude higher than the concentration required for anti-proliferative activity (5microM). Our results indicate that an increase in oxidative stress is not the main mechanism of action of Nifurtimox. Among the studied N-oxide-containing heterocycles, benzofuroxan derivatives strongly inhibited parasite dehydrogenase activity and affected mitochondrial membrane potential. The indazole derivative raised intracellular oxidants production, but it was the least effective as anti-T. cruzi. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Mechanistic insights into mode of action of potent natural antagonists of BACE-1 for checking Alzheimer’s plaque pathology

    Energy Technology Data Exchange (ETDEWEB)

    Dhanjal, Jaspreet Kaur [School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067 (India); Goyal, Sukriti [Apaji Institute of Mathematics and Applied Computer Technology, Banasthali University, Tonk 304022, Rajasthan (India); Sharma, Sudhanshu [Department of Biotechnology, Delhi Technological University, New Delhi 110042 (India); Hamid, Rabia [Department of Biochemistry, University of Kashmir, Srinagar 190006 (India); Grover, Abhinav, E-mail: abhinavgr@gmail.com [School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067 (India)

    2014-01-17

    Highlights: •Accumulation of Aβ plaques is one of the major pathology associated with Alzheimer’s disease. •Inhibition of β-Secretase or BACE-1 offers a viable prospect to check the growth of these plaques. •A large virtual dataset of natural compounds was screened against BACE-1. •Top two hits were analyzed for thermodynamic and structural stability using MD simulations. •Their detailed binding mode of actions were elucidated. -- Abstract: Alzheimer’s is a neurodegenerative disorder resulting in memory loss and decline in cognitive abilities. Accumulation of extracellular beta amyloidal plaques is one of the major pathology associated with this disease. β-Secretase or BACE-1 performs the initial and rate limiting step of amyloidic pathway in which 37–43 amino acid long peptides are generated which aggregate to form plaques. Inhibition of this enzyme offers a viable prospect to check the growth of these plaques. Numerous efforts have been made in recent years for the generation of BACE-1 inhibitors but many of them failed during the preclinical or clinical trials due to drug related or drug induced toxicity. In the present work, we have used computational methods to screen a large dataset of natural compounds to search for small molecules having BACE-1 inhibitory activity with low toxicity to normal cells. Molecular dynamics simulations were performed to analyze molecular interactions between the screened compounds and the active residues of the enzyme. Herein, we report two natural compounds of inhibitory nature active against β-secretase enzyme of amyloidic pathway and are potent lead molecules against Alzheimer’s disease.

  9. A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

    Science.gov (United States)

    Feltelius, N; Persson, I; Ahlqvist-Rastad, J; Andersson, M; Arnheim-Dahlström, L; Bergman, P; Granath, F; Adori, C; Hökfelt, T; Kühlmann-Berenzon, S; Liljeström, P; Maeurer, M; Olsson, T; Örtqvist, Å; Partinen, M; Salmonson, T; Zethelius, B

    2015-10-01

    In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar

  10. New insights into the structure and mode of action of Mo-CBP3, an antifungal chitin-binding protein of Moringa oleifera seeds.

    Directory of Open Access Journals (Sweden)

    Adelina B Batista

    Full Text Available Mo-CBP3 is a chitin-binding protein purified from Moringa oleifera Lam. seeds that displays inhibitory activity against phytopathogenic fungi. This study investigated the structural properties and the antifungal mode of action of this protein. To this end, circular dichroism spectroscopy, antifungal assays, measurements of the production of reactive oxygen species and microscopic analyses were utilized. Mo-CBP3 is composed of 30.3% α-helices, 16.3% β-sheets, 22.3% turns and 30.4% unordered forms. The Mo-CBP3 structure is highly stable and retains its antifungal activity regardless of temperature and pH. Fusarium solani was used as a model organism for studying the mechanisms by which this protein acts as an antifungal agent. Mo-CBP3 significantly inhibited spore germination and mycelial growth at 0.05 mg.mL-1. Mo-CBP3 has both fungistatic and fungicidal effects, depending on the concentration used. Binding of Mo-CBP3 to the fungal cell surface is achieved, at least in part, via electrostatic interactions, as salt was able to reduce its inhibitory effect. Mo-CBP3 induced the production of ROS and caused disorganization of both the cytoplasm and the plasma membrane in F. solani cells. Based on its high stability and specific toxicity, with broad-spectrum efficacy against important phytopathogenic fungi at low inhibitory concentrations but not to human cells, Mo-CBP3 has great potential for the development of new antifungal drugs or transgenic crops with enhanced resistance to phytopathogens.

  11. Toxicity ranking and toxic mode of action evaluation of commonly used agricultural adjuvants on the basis of bacterial gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Ingrid Nobels

    used agricultural adjuvants based on toxicity and toxic mode of action data.

  12. New insights into the structure and mode of action of Mo-CBP3, an antifungal chitin-binding protein of Moringa oleifera seeds.

    Science.gov (United States)

    Batista, Adelina B; Oliveira, José T A; Gifoni, Juliana M; Pereira, Mirella L; Almeida, Marina G G; Gomes, Valdirene M; Da Cunha, Maura; Ribeiro, Suzanna F F; Dias, Germana B; Beltramini, Leila M; Lopes, José Luiz S; Grangeiro, Thalles B; Vasconcelos, Ilka M

    2014-01-01

    Mo-CBP3 is a chitin-binding protein purified from Moringa oleifera Lam. seeds that displays inhibitory activity against phytopathogenic fungi. This study investigated the structural properties and the antifungal mode of action of this protein. To this end, circular dichroism spectroscopy, antifungal assays, measurements of the production of reactive oxygen species and microscopic analyses were utilized. Mo-CBP3 is composed of 30.3% α-helices, 16.3% β-sheets, 22.3% turns and 30.4% unordered forms. The Mo-CBP3 structure is highly stable and retains its antifungal activity regardless of temperature and pH. Fusarium solani was used as a model organism for studying the mechanisms by which this protein acts as an antifungal agent. Mo-CBP3 significantly inhibited spore germination and mycelial growth at 0.05 mg.mL-1. Mo-CBP3 has both fungistatic and fungicidal effects, depending on the concentration used. Binding of Mo-CBP3 to the fungal cell surface is achieved, at least in part, via electrostatic interactions, as salt was able to reduce its inhibitory effect. Mo-CBP3 induced the production of ROS and caused disorganization of both the cytoplasm and the plasma membrane in F. solani cells. Based on its high stability and specific toxicity, with broad-spectrum efficacy against important phytopathogenic fungi at low inhibitory concentrations but not to human cells, Mo-CBP3 has great potential for the development of new antifungal drugs or transgenic crops with enhanced resistance to phytopathogens.

  13. Control of postharvest soft rot caused by Erwinia carotovora of vegetables by a strain of Bacillus amyloliquefaciens and its potential modes of action.

    Science.gov (United States)

    Zhao, Yancun; Li, Pengxia; Huang, Kaihong; Wang, Yuning; Hu, Huali; Sun, Ya

    2013-03-01

    Erwinia carotovora subsp. carotovora (Ecc), the causal agent of bacterial soft rot, is one of the destructive pathogens of postharvest vegetables. In this study, a bacterial isolate (BGP20) from the vegetable farm soil showed strong antagonistic activity against Ecc in vitro, and its twofold cell-free culture filtrate showed excellent biocontrol effect in controlling the postharvest bacterial soft rot of potatoes at 25 °C. The anti-Ecc metabolites produced by the isolate BGP20 had a high resistance to high temperature, UV-light and protease K. Based on the colonial morphology, cellular morphology, sporulation, and partial nucleotide sequences of 16S rRNA and gyrB gene, the isolate BGP20 was identified as Bacillus amyloliquefaciens subsp. plantarum. Further in vivo assays showed that the BGP20 cell culture was more effective in controlling the postharvest bacterial soft rot of green peppers and Chinese cabbages than its twofold cell-free culture filtrate. In contrast, the biocontrol effect and safety of the BGP20 cell culture were very poor on potatoes. In the wounds of potatoes treated with both the antagonist BGP20 and the pathogen Ecc, the viable count of Ecc was 31,746 times that of BGP20 at 48 h of incubation at 25 °C. But in the wounds of green peppers, the viable count of BGP20 increased 182.3 times within 48 h, and that of Ecc increased only 51.3 %. In addition, the treatment with both BGP20 and Ecc induced higher activity of phenylalanine ammonia-lyase (PAL) than others in potatoes. But the same treatment did not induce an increase of PAL activity in green peppers. In conclusion, the present study demonstrated that the isolate BGP20 is a promising candidate in biological control of postharvest bacterial soft rot of vegetables, but its main mode of action is different among various vegetables.

  14. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  15. Thymus vulgaris essential oil and thymol against Alternaria alternata (Fr.) Keissler: effects on growth, viability, early infection and cellular mode of action.

    Science.gov (United States)

    Perina, Fabiano J; Amaral, Douglas C; Fernandes, Rafael S; Labory, Claudia Rg; Teixeira, Glauco A; Alves, Eduardo

    2015-10-01

    In initial assays, Thymus vulgaris essential oil (TEO) has demonstrated activity against several plant-pathogenic fungi and has reduced the fungal diseases to levels comparable with commercial fungicides. Thus, the goal of this work was to identify the mode of action in fungi of TEO and its major compound thymol (TOH) at the cellular level using an ultrastructure approach. TEO from leaves and TOH had minimum inhibitory concentrations (MICs) of 500 and 250 µg mL(-1) respectively against A. alternata; under the same conditions, MIC for a commercial fungicide was 1250 µg mL(-1) . Ultrastructure analysis showed that TOH phenolic substance prevented fungal growth, reduced fungal viability and prevented the penetration in fruits by a cell wall/plasma membrane interference mode of action with organelles targeted for destruction in the cytoplasm. Such mode of action differs from protective and preventive-curative commercial fungicides used as pattern control. These findings suggest that TOH was responsible for the antifungal activity of TEO. Therefore, both the essential oil and its major substance have potential for use in the development of new phenolic structures and analogues to control Alternaria brown spot disease caused by Alternaria alternata. © 2014 Society of Chemical Industry.

  16. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Directory of Open Access Journals (Sweden)

    Victoria S Paulsen

    Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  17. Marine neurotoxins: State of the art, bottlenecks, and perspectives for mode of action based methods of detection in seafood

    NARCIS (Netherlands)

    Nicolas, J.; Hendriksen, P.J.M.; Gerssen, A.; Bovee, T.F.H.; Rietjens, I.M.C.M.

    2014-01-01

    Marine biotoxins can accumulate in fish and shellfish, representing a possible threat for consumers. Many marine biotoxins affect neuronal function essentially through their interaction with ion channels or receptors, leading to different symptoms including paralysis and even death. The detection of

  18. Dynamics of regional brain activity in epilepsy: a cross-disciplinary study on both intracranial and scalp-recorded epileptic seizures

    Science.gov (United States)

    Minadakis, George; Ventouras, Errikos; Gatzonis, Stylianos D.; Siatouni, Anna; Tsekou, Hara; Kalatzis, Ioannis; Sakas, Damianos E.; Stonham, John

    2014-04-01

    Objective. Recent cross-disciplinary literature suggests a dynamical analogy between earthquakes and epileptic seizures. This study extends the focus of inquiry for the applicability of models for earthquake dynamics to examine both scalp-recorded and intracranial electroencephalogram recordings related to epileptic seizures. Approach. First, we provide an updated definition of the electric event in terms of magnitude and we focus on the applicability of (i) a model for earthquake dynamics, rooted in a nonextensive Tsallis framework, (ii) the traditional Gutenberg and Richter law and (iii) an alternative method for the magnitude-frequency relation for earthquakes. Second, we apply spatiotemporal analysis in terms of nonextensive statistical physics and we further examine the behavior of the parameters included in the nonextensive formula for both types of electroencephalogram recordings under study. Main results. We confirm the previously observed power-law distribution, showing that the nonextensive formula can adequately describe the sequences of electric events included in both types of electroencephalogram recordings. We also show the intermittent behavior of the epileptic seizure cycle which is analogous to the earthquake cycles and we provide evidence of self-affinity of the regional electroencephalogram epileptic seizure activity. Significance. This study may provide a framework for the analysis and interpretation of epileptic brain activity and other biological phenomena with similar underlying dynamical mechanisms.

  19. Post-genomic science: cross-disciplinary and large-scale collaborative research and its organizational and technological challenges for the scientific research process.

    Science.gov (United States)

    Welsh, Elaine; Jirotka, Marina; Gavaghan, David

    2006-06-15

    We examine recent developments in cross-disciplinary science and contend that a 'Big Science' approach is increasingly evident in the life sciences-facilitated by a breakdown of the traditional barriers between academic disciplines and the application of technologies across these disciplines. The first fruits of 'Big Biology' are beginning to be seen in, for example, genomics, (bio)-nanotechnology and systems biology. We suggest that this has profound implications for the research process and presents challenges both in technological design, in the provision of infrastructure and training, in the organization of research groups, and in providing suitable research funding mechanisms and reward systems. These challenges need to be addressed if the promise of this approach is to be fully realized. In this paper, we will draw on the work of social scientists to understand how these developments in science and technology relate to organizational culture, organizational change and the context of scientific work. We seek to learn from previous technological developments that seemed to offer similar potential for organizational and social change.

  20. From Multi-Sensors Observations Towards Cross-Disciplinary Study of Pre-Earthquake Signals. What have We Learned from the Tohoku Earthquake?

    Science.gov (United States)

    Ouzounov, D.; Pulinets, S.; Papadopoulos, G.; Kunitsyn, V.; Nesterov, I.; Hayakawa, M.; Mogi, K.; Hattori, K.; Kafatos, M.; Taylor, P.

    2012-01-01

    The lessons we have learned from the Great Tohoku EQ (Japan, 2011) how this knowledge will affect our future observation and analysis is the main focus of this presentation.We present multi-sensors observations and multidisciplinary research in our investigation of phenomena preceding major earthquakes. These observations revealed the existence of atmospheric and ionospheric phenomena occurring prior to theM9.0 Tohoku earthquake of March 11, 2011, which indicates s new evidence of a distinct coupling between the lithosphere and atmosphere/ionosphere, as related to underlying tectonic activity. Similar results have been reported before the catastrophic events in Chile (M8.8, 2010), Italy (M6.3, 2009) and Sumatra (M9.3, 2004). For the Tohoku earthquake, our analysis shows a synergy between several independent observations characterizing the state of the lithosphere /atmosphere coupling several days before the onset of the earthquakes, namely: (i) Foreshock sequence change (rate, space and time); (ii) Outgoing Long wave Radiation (OLR) measured at the top of the atmosphere; and (iii) Anomalous variations of ionospheric parameters revealed by multi-sensors observations. We are presenting a cross-disciplinary analysis of the observed pre-earthquake anomalies and will discuss current research in the detection of these signals in Japan. We expect that our analysis will shed light on the underlying physics of pre-earthquake signals associated with some of the largest earthquake events

  1. MDO and Cross-Disciplinary Practice in R&D: A Portrait of Principles and Current Practice

    Science.gov (United States)

    Rivas McGowan, Anna-Maria; Papalambros, Panos Y.; Baker, Wayne E.

    2014-01-01

    For several decades, Multidisciplinary Design Optimization (MDO) has served an important role in aerospace engineering by incorporating physics based disciplinary models into integrated system or sub-system models for use in research, development, (R&D) and design. This paper examines MDO's role in facilitating the integration of the researchers from different single disciplines during R&D and early design of large-scale complex engineered systems (LaCES) such as aerospace systems. The findings in this paper are summarized from a larger study on interdisciplinary practices and perspectives that included considerable empirical data from surveys, interviews, and ethnography. The synthesized findings were derived by integrating the data with theories from organization science and engineering. The over-arching finding is that issues related to cognition, organization, and social interrelations mostly dominate interactions across disciplines. Engineering issues, such as the integration of hardware or physics-based models, are not as significant. Correspondingly, the data showed that MDO is not the primary integrator of researchers working across disciplines during R&D and early design of LaCES. Cognitive focus such as analysis versus design, organizational challenges such as incentives, and social opportunities such as personal networks often drove the human interactive practices among researchers from different disciplines. Facilitation of the inherent confusion, argument, and learning in crossdisciplinary research was identified as one of several needed elements of enabling successful research across disciplines.

  2. Where High-Tech Meets High-Touch: an example of effective cross-disciplinary collaboration in education

    Science.gov (United States)

    Holzhauer, B.; Mooney, M. E.

    2012-12-01

    How can non-formal education programs effectively blend hands-on, place-based field science lessons with technology and digital media to teach abstract global concepts in a local setting? Using climate change as an overarching concept, the Aldo Leopold Nature Center (ALNC) in Madison, WI, is developing exhibits and digital curricula, strengthened through partnerships with local and national experts from scientific and education fields, to effectively increase the public's interest in and understanding of science and technology, how the world works, and what we can do to adapt, mitigate, and innovate sustainable solutions. The exhibits and multimedia content, centered on topics such as climate, energy, weather, and phenology, have been developed in consultation with partners like the National Academy of Sciences and various departments at the University of Wisconsin (UW). Outdoor "high-touch" programs are complemented with "high-tech" exhibits and media, including touchscreen kiosks and the National Oceanic and Atmospheric Administration's (NOAA) Science On a Sphere® global display system, tying together multimedia experiences with peer-reviewed cutting-edge science to ensure maximum comprehension by appealing and connecting to learners of all ages and learning modalities. The curriculum is being developed in alignment with local and national education standards and science and climate literacy frameworks (such as "The Essential Principles of Climate Sciences," U.S. Global Change Research Program / U.S. Climate Change Science Program). Its digital format allows it to be easily adapted to visitors' learning styles and cognitive levels and updated with relevant new content such as real-time climate data or current visualizations from the UW Cooperative Institute for Meteorological Satellite Studies. Drawing upon ALNC's award-winning environmental education experiences, professional development networks such as NOAA's Climate Stewards Education Program, and existing

  3. Cross-Disciplinary Perceptions of Structured Interprofessional Rounds in Promoting Teamwork Within an Academic Tertiary Care Obstetric Unit.

    Science.gov (United States)

    Chau, Anthony; Vijjeswarapu, Mary A; Hickey, Margaret; Acker, David; Huang, Chuan-Chin; Tsen, Lawrence C

    2017-06-01

    In 2005, physician and nursing leaders at Brigham and Women's Hospital initiated structured interprofessional rounds (SIPRs) on the labor and delivery (L&D) suite to improve team communication. We performed a cross-sectional analysis of providers' perceptions of SIPRs and their effectiveness in improving teamwork. We hypothesized that on average, providers would perceive SIPRs as being effective in promoting teamwork, but ratings would differ among professional groups. After a factor analysis and internal consistency assessment, a 19-item paper-based questionnaire was used to evaluate providers' perceptions using a 5-point Likert scale. Respondents included L&D nurses, midwives, obstetricians, and anesthesiologists who participate in SIPRs. The primary aim was to evaluate the providers' perceptions of SIPRs and their association with professional roles. The outcome was total response score for each provider, ranging from 19 to 95; perception of SIPRs as being effective in promoting teamwork was defined as having a total response score of >66.5 (mean score, >3.5 per question). A univariable linear regression model was performed, followed by a multivariable analysis adjusting for predictors that modified the outcome; predictors included years of professional practice, years of experience on the L&D suite, number of clinical work hours worked weekly, and principal shift assignment among nurses. The associations between these predictors and providers' perceptions were assessed as a secondary aim. A total of 234 practitioners responded (100% response rate). The mean total response score (SD) for all providers was 73.3 (9.5). After multivariable adjustment, the mean total response scores were significantly higher for obstetric providers than for anesthesia (Δ mean, 6.5, 95% CI, 0.3, 12.7 P = .036) and midwifery (Δ mean, 12.5, 95% CI, 2.0, 23.0, P = .009) providers. Providers scored significantly lower if they worked >60 clinical hours per week compared with ≤20 (

  4. Lowering the Barrier to Cross-Disciplinary Scientific Data Access via a Brokering Service Built Around a Unified Data Model

    Science.gov (United States)

    Lindholm, D. M.; Wilson, A.

    2012-12-01

    The steps many scientific data users go through to use data (after discovering it) can be rather tedious, even when dealing with datasets within their own discipline. Accessing data across domains often seems intractable. We present here, LaTiS, an Open Source brokering solution that bridges the gap between the source data and the user's code by defining a unified data model plus a plugin framework for "adapters" to read data from their native source, "filters" to perform server side data processing, and "writers" to output any number of desired formats or streaming protocols. A great deal of work is being done in the informatics community to promote multi-disciplinary science with a focus on search and discovery based on metadata - information about the data. The goal of LaTiS is to go that last step to provide a uniform interface to read the dataset into computer programs and other applications once it has been identified. The LaTiS solution for integrating a wide variety of data models is to return to mathematical fundamentals. The LaTiS data model emphasizes functional relationships between variables. For example, a time series of temperature measurements can be thought of as a function that maps a time to a temperature. With just three constructs: "Scalar" for a single variable, "Tuple" for a collection of variables, and "Function" to represent a set of independent and dependent variables, the LaTiS data model can represent most scientific datasets at a low level that enables uniform data access. Higher level abstractions can be built on top of the basic model to add more meaningful semantics for specific user communities. LaTiS defines its data model in terms of the Unified Modeling Language (UML). It also defines a very thin Java Interface that can be implemented by numerous existing data interfaces (e.g. NetCDF-Java) such that client code can access any dataset via the Java API, independent of the underlying data access mechanism. LaTiS also provides a

  5. The first toxicological study of the antiozonant and research tool ethylene diurea (EDU) using a Lemna minor L. bioassay: Hints to its mode of action.

    Science.gov (United States)

    Agathokleous, Eugenios; Mouzaki-Paxinou, Akrivi-Chara; Saitanis, Costas J; Paoletti, Elena; Manning, William J

    2016-06-01

    The antiozonant and research tool ethylene diurea (EDU) is widely studied as a phytoprotectant against the widespread pollutant ground-surface ozone. Although it has been extensively used, its potential toxicity in the absence of ozone is unknown and its mode of action is unclear. The purpose of this research was to toxicologically assess EDU and to further investigate its mode of action using Lemna minor L. as a model organism. Application of EDU concentrations greater than 593 mg L(-1) (practically 600 mg L(-1)) resulted in adverse inhibition of colony growth. As no-observed-toxic-effects concentration (NOEL) we recommend a concentration of 296 mg L(-1) (practically 300 mg L(-1)). A hormetic response was detected, i.e. stimulatory effects of low EDU concentrations, which may indicate overcompensation in response to disruption in homeostasis. Growth inhibition and suppressed biomass were associated with impacted chlorophyll a fluorescence (ΦPSII, qP and ETR). Furthermore, EDU increased mesophyll thickness, as indicated by frond succulence index. Applications of concentrations ≥593 mg L(-1) to uncontrolled environments should be avoided due to potential toxicity to sensitive organisms and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Partial Purification and Characterization of the Mode of Action of Enterocin S37: A Bacteriocin Produced by Enterococcus faecalis S37 Isolated from Poultry Feces

    Directory of Open Access Journals (Sweden)

    Y. Belguesmia

    2010-01-01

    Full Text Available The aim of this research was to purify and characterize the mode of action of enterocin S37, a bacteriocin produced by Enterococcus faecalis S37, a strain recently isolated from the chicken feces. Enterocin S37 has a molecular weight comprised between 4 and 5 kDa. It remained active after 1 h at 80oC and at pH values ranging from 4.0 to 9.0. Furthermore, cell-free supernatant of Enterococcus faecalis S37 and purified enterocin S37 were active against Gram-positive bacteria including Listeria monocytogenes EGDe, L. innocua F, Enterococcus faecalis JH2-2, and Lactobacillus brevis F145. The purification of enterocin S37 was performed by ammonium sulfate precipitation followed up by hydrophobic-interaction chromatography procedures. Treatment of enterocin S37 with proteinase K, -chymotrypsin, and papain confirmed its proteinaceous nature, while its treatment with lysozyme and lipase resulted in no alteration of activity. Enterocin S37 is hydrophobic, anti-Listeria and likely acting by depletion of intracellular K+ ions upon action on KATP channels. This study contributed to gain more insights into the mode of action of enterocins.

  7. Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study.

    Science.gov (United States)

    de Castro, Ricardo Dias; de Souza, Trícia Murielly Pereira Andrade; Bezerra, Louise Morais Dornelas; Ferreira, Gabriela Lacet Silva; Costa, Edja Maria Melo de Brito; Cavalcanti, Alessandro Leite

    2015-11-24

    Limitations of antifungal agents used in the treatment of oral candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to evaluate the antifungal activity of thymol against Candida albicans, Candida tropicalis and Candida krusei strains and to determine its mode of action and synergistic effect when combined with the synthetic antifungal nystatin. The minimum inhibitory concentration (MIC) was determined using a microdilution technique, and the minimum fungicidal concentration (MFC) was determined via subculture sowing. The mode of action of thymol was established by verifying fungal growth in the presence of sorbitol or ergosterol. The fractional inhibitory concentration index (FIC) was determined using the checkerboard method. Thymol presented an antifungal effect, with MICs of 39 μg/mL for C. albicans and C. krusei and 78 μg/mL for C. tropicalis. The results of the antifungal test remained unchanged in the presence of sorbitol; however, the MIC value of thymol against C. albicans increased eight times (from 39.0 to 312.5 μg/mL) in presence of exogenous ergosterol. The combination of thymol and nystatin reduced the MIC values of both products by 87.4%, generating an FIC index of 0.25. Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with nystatin.

  8. Mode of action of leucocin K7 produced by Leuconostoc mesenteroides K7 against Listeria monocytogenes and its potential in milk preservation.

    Science.gov (United States)

    Shi, Feng; Wang, Yanwei; Li, Yongfu; Wang, Xiaoyuan

    2016-09-01

    To investigate the mode of action of leucocin K7 against Listeria monocytogenes and to assess its inhibitory effect on Lis. monocytogenes in refrigerated milk. A bacteriocin-producing strain, Leuconostoc mesenteroides K7, was isolated from a fermented pickle. The bacteriocin, leucocin K7, exhibited antagonistic activity against Lis. monocytogenes with an MIC of 28 µg/ml. It was sensitive to proteaseS and displayed good thermal stability and broad active pH range. Leucocin K7 had no effect on the efflux of ATP from Lis. monocytogenes but triggered the efflux of K(+) and the intracellular hydrolysis of ATP. It also dissipated the transmembrane electrical potential completely and transmembrane pH gradient partially. It 80 AU/ml inhibited the growth of Lis. monocytogenes by 2.3-3.9 log units in milk; when combined with glycine (5 mg/ml), it completely eliminated viable Lis. monocytogenes over 7 days Leucocin K7 shows different mode of action from nisin and may have potential application in milk preservation.

  9. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  10. Biological control of the cucurbit powdery mildew pathogen Podosphaera xanthii by means of the epiphytic fungus Pseudozyma aphidis and parasitism as a mode of action

    Directory of Open Access Journals (Sweden)

    Aviva eGafni

    2015-03-01

    Full Text Available Epiphytic yeasts, which colonize plant surfaces, may possess activity that can be harnessed to help plants defend themselves against various pathogens. Due to their unique characteristics, epiphytic yeasts belonging to the genus Pseudozyma hold great potential for use as biocontrol agents. We identified a unique, biologically active isolate of the epiphytic yeast Pseudozyma aphidis that is capable of inhibiting Botrytis cinerea via a dual mode of action, namely induced resistance and antibiosis. Here, we show that strain L12 of P. aphidis can reduce the severity of powdery mildew caused by Podosphaera xanthii on cucumber plants with an efficacy of 75%. Confocal and scanning electron microscopy analyses demonstrated P. aphidis proliferation on infected tissue and its production of long hyphae that parasitize the powdery mildew hyphae and spores as an ectoparasite. We also show that crude extract of P. aphidis metabolites can inhibit P. xanthii spore germination in planta. Our results suggest that in addition to its antibiosis mode of action, P. aphidis may also act as an ectoparasite on P. xanthii. These results indicate that P. aphidis strain L12 has the potential to control powdery mildew.

  11. The economic importance of acaricides in the control of phytophagous mites and an update on recent acaricide mode of action research.

    Science.gov (United States)

    Van Leeuwen, Thomas; Tirry, Luc; Yamamoto, Atsushi; Nauen, Ralf; Dermauw, Wannes

    2015-06-01

    Acaricides are one of the cornerstones of an efficient control program for phytophagous mites. An analysis of the global acaricide market reveals that spider mites such as Tetranychus urticae, Panonychus citri and Panonychus ulmi are by far the most economically important species, representing more than 80% of the market. Other relevant mite groups are false spider mites (mainly Brevipalpus), rust and gall mites and tarsonemid mites. Acaricides are most frequently used in vegetables and fruits (74% of the market), including grape vines and citrus. However, their use is increasing in major crops where spider mites are becoming more important, such as soybean, cotton and corn. As revealed by a detailed case study of the Japanese market, major shifts in acaricide use are partially driven by resistance development and the commercial availability of compounds with novel mode of action. The importance of the latter cannot be underestimated, although some compounds are successfully used for more than 30 years. A review of recent developments in mode of action research is presented, as such knowledge is important for devising resistance management programs. This includes spirocyclic keto-enols as inhibitors of acetyl-CoA carboxylase, the carbazate bifenazate as a mitochondrial complex III inhibitor, a novel class of complex II inhibitors, and the mite growth inhibitors hexythiazox, clofentezine and etoxazole that interact with chitin synthase I. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Design thinking - crossing disciplinary borders

    CSIR Research Space (South Africa)

    Viljoen, NM

    2009-01-01

    Full Text Available /MS. Human-centred in focus/empathy. Design is client and user directed. Designers imagine the world from multiple viewpoints and imagine appropriate solutions for these viewpoints (Brown 2008:87). Design solutions are also adaptive to the evolving needs... of design thinking for OR/MS is empathy; this refers to the ability to observe reality from multiple viewpoints. Empathy can in turn lead to imagined solutions for these multiple viewpoints (Brown 2008:87). It becomes clear when comparing Figures 2 and 4...

  13. Use of electroencephalography (EEG) to assess CNS changes produced by pesticides with different modes of action: Effects of permethrin, deltamethrin, fipronil, imidacloprid, carbaryl, and triadimefon

    Energy Technology Data Exchange (ETDEWEB)

    Freeborn, Danielle L., E-mail: Freeborn.danielle@epa.gov; McDaniel, Katherine L., E-mail: McDaniel.kathy@epa.gov; Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Herr, David W., E-mail: Herr.david@epa.gov

    2015-01-15

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long–Evans rats. The EEG was recorded using two montages (visual cortex referenced to the cerebellum and to the frontal cortex) in unrestrained rats at the time of peak behavioral effects. Pesticides included: permethrin and deltamethrin (Type I and Type II pyrethroids; 2 h), fipronil (single and repeated doses; phenylpyrazole; 6 h), imidacloprid (neonicotinoid; 2 h), carbaryl (carbamate; 0.5 h), and triadimefon (triazole; 1 h), using dosages that produced approximately an ED{sub 30} or an ED{sub 50}–ED{sub 80} change in motor activity. Permethrin (43, 100 mg/kg) increased amplitudes or areas (delta, alpha, or gamma bands) in the EEG. Deltamethrin (2.5, 5.5 mg/kg) reduced the amplitudes or areas of the delta, theta, alpha, beta, and gamma bands, but the changes were not dose-related. A single treatment with fipronil (25, 50 mg/kg, but not 5, 10 mg/kg) decreased gamma band area. Additional changes in the delta, theta, and gamma bands were observed when fipronil (5, 10 mg/kg) was administered for 14 days. Imidacloprid (50, 100 mg/kg) did not alter the EEG. Carbaryl (10, 50 mg/kg) decreased theta area, and decreased delta and increased beta frequency. Triadimefon (75, 150 mg/kg) produced minimal changes in the EEG. The results show that the EEG is affected differently by approximately equipotent doses of pesticides with different modes of action. - Highlights: • Pesticides with different modes of action have different effects on in vivo rodent EEG. • The EEG was also changed differently after single vs. repeated treatment with fipronil. • The data suggest that EEG may be used as an apical measure for detecting chemical effects on the central nervous system.

  14. Use of the antiozonant ethylenediurea (EDU) in Italy: verification of the effects of ambient ozone on crop plants and trees and investigation of EDU's mode of action.

    Science.gov (United States)

    Paoletti, Elena; Contran, Nicla; Manning, William J; Ferrara, Anna M

    2009-05-01

    Twenty-four experiments where EDU was used to protect plants from ozone (O(3)) in Italy are reviewed. Doses of 150 and 450 ppm EDU at 2-3 week intervals were successfully applied to alleviate O(3)-caused visible injury and growth reductions in crop and forest species respectively. EDU was mainly applied as soil drench to crops and by stem injection or infusion into trees. Visible injury was delayed and reduced but not completely. In investigations on mode of action, EDU was quickly (8 days), as it cannot move via phloem. EDU did not enter cells, suggesting it does not directly affect cell metabolism. EDU delayed senescence, did not affect photosynthesis and foliar nitrogen content, and stimulated antioxidant responses to O(3) exposure. Preliminary results suggest developing an effective soil application method for forest trees is warranted.

  15. Use of electroencephalography (EEG) to assess CNS changes produced by pesticides with different modes of action: effects of permethrin, deltamethrin, fipronil, imidacloprid, carbaryl, and triadimefon.

    Science.gov (United States)

    Freeborn, Danielle L; McDaniel, Katherine L; Moser, Virginia C; Herr, David W

    2015-01-15

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long-Evans rats. The EEG was recorded using two montages (visual cortex referenced to the cerebellum and to the frontal cortex) in unrestrained rats at the time of peak behavioral effects. Pesticides included: permethrin and deltamethrin (Type I and Type II pyrethroids; 2 h), fipronil (single and repeated doses; phenylpyrazole; 6 h), imidacloprid (neonicotinoid; 2 h), carbaryl (carbamate; 0.5 h), and triadimefon (triazole; 1 h), using dosages that produced approximately an ED30 or an ED50-ED80 change in motor activity. Permethrin (43, 100 mg/kg) increased amplitudes or areas (delta, alpha, or gamma bands) in the EEG. Deltamethrin (2.5, 5.5 mg/kg) reduced the amplitudes or areas of the delta, theta, alpha, beta, and gamma bands, but the changes were not dose-related. A single treatment with fipronil (25, 50 mg/kg, but not 5, 10 mg/kg) decreased gamma band area. Additional changes in the delta, theta, and gamma bands were observed when fipronil (5, 10 mg/kg) was administered for 14 days. Imidacloprid (50, 100 mg/kg) did not alter the EEG. Carbaryl (10, 50 mg/kg) decreased theta area, and decreased delta and increased beta frequency. Triadimefon (75, 150 mg/kg) produced minimal changes in the EEG. The results show that the EEG is affected differently by approximately equipotent doses of pesticides with different modes of action. Published by Elsevier Inc.

  16. Coriandrum sativum L. (Coriander essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    Directory of Open Access Journals (Sweden)

    Irlan de Almeida Freires

    Full Text Available Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis, as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  17. Probable neuro sexual mode of action of Casimiroa edulis seed extract versus [correction of verses] sildenafil citrate (Viagra(tm)) on mating behavior in normal male rats.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2008-01-01

    The present study deals with the aphrodisiac actions of the aqueous extract of the seeds of the hypotensive plant Casimiroa edulis on the sexual behavior of normal male rats. In this investigation 30 healthy male Wister strain white albino rats showing the brisk sexual activity age 15 weeks, weighing 400-450 grams were included. Female rats were artificially brought into estrous by hormonal treatment. Receptivity was checked by exposing them to the male rats and the most receptive females were selected for the stud The mating responses including Mounting Frequency (MF), Intromission Frequency (IF), Mounting Latency (ML), Intromission Latency (IL), Ejaculatory Latency in first and second series (EL1 and EL2) and Post Ejaculatory Interval (PEI) were recorded after treating the animals with 250 mg/kg casimiroa edulis extract (test reference) and 5 mg/kg sildenafil citrate (standard reference) respectively orally per day for 7 days. Both the groups exhibited a significant increase in Mounting Frequency, Intromission Frequency, and first and second ejaculatory latencies, where as Mounting and Intromission latencies and the Post Ejaculatory Interval showed a significant reduction than the controls. Although a similar pattern of mating behavior was observed among the test and the standard groups, however in all the cases as expected, sildenafil produced greater activity than the casimiroa edulis extract. These results suggest the possibility of a similar mode of action of casimiroa edulis and sildenafil citrate on mating behavior in these animals. Our work reported in this research thus provide preliminary evidence that the aqueous seed extract of casimiroa edulis possesses alphrodisiac activity and may be used as an alternative drug therapy to restore sexual functions probably via a neurogenic mode of action.

  18. Significando o risco sanitário: modos de atuação sobre o risco na vigilância sanitária / Meaning the health risk: modes of action on the risk in health surveillance

    Directory of Open Access Journals (Sweden)

    Ana Valesca Fernandes GIlson Silva

    2014-05-01

    intervention there are processes that mixture the rationality, subjectivity, authority, control, experience, the formal knowledge acquired. The act of the HS professional consists of knowledge, acquired experience, socio-cultural contexts, and interactions that define and redefine the modes of action. The actions are based on the meanings of the risk that moves in the planes of objectivity and subjectivity and, the legislation is an important instrument of decision and persuasion. Although there is an offset to the use of the knowledge and experience, it is the legal framework that prints what should or should not be controlled.

  19. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development (SETAC abstract)

    Science.gov (United States)

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limit...

  20. Comparative Systems Biology Analysis To Study the Mode of Action of the Isothiocyanate Compound Iberin on Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Tan, Sean Yang-Yi; Liu, Yang; Chua, Song Lin

    2014-01-01

    each other and provide a thorough overview of the impact of iberin on P. aeruginosa. RNA sequencing-based transcriptomics showed that iberin inhibits the expression of the GacA-dependent small regulatory RNAs RsmY and RsmZ; this was verified by using gfp-based transcriptional reporter fusions...... Pseudomonas aeruginosa. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of P. aeruginosa. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement....../Rsm QS network, which in turn leads to the repression of QS-regulated virulence factors, such as pyoverdine, chitinase, and protease IV. Lastly, as expected from the observed repression of small regulatory RNA synthesis, we also show that iberin effectively reduces biofilm formation. This suggests...

  1. Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro

    Science.gov (United States)

    Fang, Zhijia; Zhao, Min; Zhen, Hong; Chen, Lifeng; Shi, Ping; Huang, Zhiwei

    2014-01-01

    Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo. PMID:25111056

  2. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

    Directory of Open Access Journals (Sweden)

    Dominika Mániková

    2014-08-01

    Full Text Available Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the “redox link” which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

  4. The role of blood cell membrane lipids on the mode of action of HIV-1 fusion inhibitor sifuvirtide

    Energy Technology Data Exchange (ETDEWEB)

    Matos, Pedro M.; Freitas, Teresa; Castanho, Miguel A.R.B. [Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal); Santos, Nuno C., E-mail: nsantos@fm.ul.pt [Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal)

    2010-12-17

    Research highlights: {yields} Sifuvirtide interacts with erythrocyte and lymphocyte membrane in a concentration dependent manner by decreasing its dipole potential. {yields} Dipole potential variations in lipid vesicles show sifuvirtide's lipid selectivity towards saturated phosphatidylcholines. {yields} This peptide-membrane interaction may direct the drug towards raft-like membrane domains where the receptors used by HIV are located, facilitating its inhibitory action. -- Abstract: Sifuvirtide is a gp41 based peptide that inhibits HIV-1 fusion with the host cells and is currently under clinical trials. Previous studies showed that sifuvirtide partitions preferably to saturated phosphatidylcholine lipid membranes, instead of fluid-phase lipid vesicles. We extended the study to the interaction of the peptide with circulating blood cells, by using the dipole potential sensitive probe di-8-ANEPPS. Sifuvirtide decreased the dipole potential of erythrocyte and lymphocyte membranes in a concentration dependent manner, demonstrating its interaction. Also, the lipid selectivity of the peptide towards more rigid phosphatidylcholines was confirmed based on the dipole potential variations. Overall, the interaction of the peptide with the cell membranes is a contribution of different lipid preferences that presumably directs the peptide towards raft-like domains where the receptors are located, facilitating the reach of the peptide to its molecular target, the gp41 in its pre-fusion conformation.

  5. Mode of action of plectasin-derived peptides against gas gangrene-associated Clostridium perfringens type A

    Science.gov (United States)

    Zheng, Xueling; Wang, Xiumin; Teng, Da; Mao, Ruoyu; Hao, Ya; Yang, Na; Zong, Lifen

    2017-01-01

    NZ2114 and MP1102 are novel plectasin-derived peptides with potent activity against Gram-positive bacteria. The antibacterial characteristics and mechanism of NZ2114 and MP1102 against gas gangrene-associated Clostridium perfringens were studied for the first time. The minimal inhibitory concentration and minimal bactericidal concentration of NZ2114 and MP1102 against resistant C. perfringens type A strain CVCC 46 were 0.91 μM. Based on the fractional inhibitory concentration index (FICI) result, an additive or synergic effect was observed between NZ2114 (FICI = 0.5~0.75) or MP1102 (FICI = 0.375~1.0) and antibiotics. The flow cytometry, scanning and transmission electron microscopy analysis showed that both NZ2114 and MP1102 induced obviously membrane damage, such as the leakage of cellular materials, partial disappearance of the cell membrane and membrane peeling, as well as retracting cytoplasm and ghost cell. The gel retardation and circular dichroism (CD) detection showed that NZ2114 and MP1102 could bind to C. perfringens genomic DNA and change the DNA conformation. Moreover, NZ2114 also interfered with the double helix and unwind the genomic DNA. The cell cycle analysis showed that C. perfringens CVCC 46 cells exposed to NZ2114 and MP1102 were arrested at the phase I. These data indicated that both NZ2114 and MP1102 have potential as new antimicrobial agents for gas gangrene infection resulting from resistant C. perfringens. PMID:28934314

  6. The nonantibiotic anti-inflammatory effect of antimicrobial growth promoters, the real mode of action? A hypothesis.

    Science.gov (United States)

    Niewold, T A

    2007-04-01

    Societal concern and government regulations increasingly press for restricting the use of antibiotics as antimicrobial growth promoters (AGP). The search for alternatives is on, hampered by a lack of knowledge about the exact mechanism of AGP. Feed additives, such as AGP and alternatives, interact with the intestine. In the intestine, feed components, microbiota, and the mucosa interact in a very complex and dynamic way. Various mechanisms for AGP have been proposed, invariably based on the direct antibiotic influence on the microbial composition of the intestines. In the literature on antibiotics, however, the direct effects of antibiotics on host cells, in particular inflammatory cells, have been described. It is curious that this has never been considered in the literature on AGP. Presently, a case is being made that AGP most likely work as growth permitters by inhibiting the production and excretion of catabolic mediators by intestinal inflammatory cells. Concomitant or subsequent changes in microflora are most likely the consequence of an altered condition of the intestinal wall. This common, basic mechanism potentially offers an excellent explanation for the highly reproducible effects of AGP, as opposed to those obtained by alternatives aimed at microflora management. Therefore, the search for alternatives could be aimed at nonantibiotic compounds with an effect on the inflammatory system similar to that of AGP.

  7. Mode of action of plectasin-derived peptides against gas gangrene-associated Clostridium perfringens type A.

    Science.gov (United States)

    Zheng, Xueling; Wang, Xiumin; Teng, Da; Mao, Ruoyu; Hao, Ya; Yang, Na; Zong, Lifen; Wang, Jianhua

    2017-01-01

    NZ2114 and MP1102 are novel plectasin-derived peptides with potent activity against Gram-positive bacteria. The antibacterial characteristics and mechanism of NZ2114 and MP1102 against gas gangrene-associated Clostridium perfringens were studied for the first time. The minimal inhibitory concentration and minimal bactericidal concentration of NZ2114 and MP1102 against resistant C. perfringens type A strain CVCC 46 were 0.91 μM. Based on the fractional inhibitory concentration index (FICI) result, an additive or synergic effect was observed between NZ2114 (FICI = 0.5~0.75) or MP1102 (FICI = 0.375~1.0) and antibiotics. The flow cytometry, scanning and transmission electron microscopy analysis showed that both NZ2114 and MP1102 induced obviously membrane damage, such as the leakage of cellular materials, partial disappearance of the cell membrane and membrane peeling, as well as retracting cytoplasm and ghost cell. The gel retardation and circular dichroism (CD) detection showed that NZ2114 and MP1102 could bind to C. perfringens genomic DNA and change the DNA conformation. Moreover, NZ2114 also interfered with the double helix and unwind the genomic DNA. The cell cycle analysis showed that C. perfringens CVCC 46 cells exposed to NZ2114 and MP1102 were arrested at the phase I. These data indicated that both NZ2114 and MP1102 have potential as new antimicrobial agents for gas gangrene infection resulting from resistant C. perfringens.

  8. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action

    Directory of Open Access Journals (Sweden)

    Jana Subarna

    2006-02-01

    Full Text Available Abstract Background Inorganic arsenic is a major water pollutant and a known human carcinogen that has a suppressive influence on spermatogenesis and androgenesis in male reproductive system. However, the actual molecular events resulting in male reproductive dysfunctions from exposure to arsenic remain unclear. In this context, we evaluated the mode of action of chronic oral exposure of sodium arsenite on hypothalamo-pituitary- testicular activities in mature male albino rats. Methods The effect of chronic oral exposure to sodium arsenite (5 mg/kg body weight/day via drinking water without or with hCG (5 I.U./kg body weight/day and oestradiol (25 micrograms oestradiol 3-benzoate suspended in 0.25 ml olive oil/rat/day co-treatments for 6 days a week for 4 weeks (about the duration of two spermatogenic cycle was evaluated in adult male rats. Changes in paired testicular weights, quantitative study of different varieties of germ cells at stage VII of spermatogenic cycle, epididymal sperm count, circulatory concentrations of hormones (LH, FSH, testosterone and corticosterone, testicular activities of delta 5, 3beta-hydroxysteroid dehydrogenase (delta 5, 3beta-HSD, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD, sorbitol dehydrogenase (SDH, acid phosphatase (ACP, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH, as well as the levels of biogenic amines (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT in the hypothalamus and pituitary were monitored in this study. Hormones were assayed by radioimmuno- assay or enzyme- linked immunosorbent assay and the enzymes were estimated after spectrophotometry as well as the biogenic amines by HPLC electrochemistry. Results Sodium arsenite treatment resulted in: decreased paired testicular weights; epididymal sperm count; plasma LH, FSH, testosterone and testicular testosterone concentrations; and increased plasma concentration of corticosterone. Testicular enzymes such as delta 5, 3 beta

  9. QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degradation on the toxicity and mode of action of diuron in algae and daphnids.

    Science.gov (United States)

    Neuwoehner, Judith; Zilberman, Tobias; Fenner, Kathrin; Escher, Beate I

    2010-04-01

    Even though the environmental occurrence of pesticide transformation products is well established, ecotoxicological data for transformation products are often lacking. Therefore, it remains an open question for regulators how to handle transformation products in the process of authorization and risk assessment. Transformation products may (1) possess a similar mode of toxic action as the parent compound, (2) exhibit unexpected effects towards non-target organisms or (3) contribute to overall mixture toxicity through baseline toxicity even if the specific activity of the parent compound is lost. In the present study, a systematic and integrated approach is presented to differentiate between these three options with the goal of identifying transformation products that significantly add to the risk posed by the parent compound. Quantitative structure-activity relationships (QSAR) and a toxic ratio (TR) analysis were used to evaluate the toxicity and mode of toxic action of the transformation products relative to the parent compound. In addition, mixture toxicity experiments were used as diagnostic tools to underpin the mode of action analysis and to elucidate whether the transformation products possess a similar risk potential as the parent compound. As an illustrative example, the phenylurea herbicide diuron was chosen since a sound basis of ecotoxicological data was available not only for diuron itself but also for most of its transformation products. Effects were investigated using the most sensitive species, algae, and the non-target organism Daphnia magna, for which a previous QSAR-analysis of literature data suggested a specific hazard. In the present study the primary transformation products 1-(3,4-dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of the methylurea group during

  10. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Zheng, Suqing [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Huang, Jeffrey T.-J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Honda, Tadashi [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Dinkova-Kostova, Albena T., E-mail: a.dinkovakostova@dundee.ac.uk [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States)

    2015-09-25

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in

  11. Mode of action illudin S.

    Science.gov (United States)

    Walser, J; Heinstein, P F

    1973-03-01

    The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from Escherichia coli pol A(1) (-), with E. coli DNA-dependent RNA polymerase, with E. coli pol A(1) (-) spheroplasts, and with frozen and thawed Bacillus subtilis cells. A protein fraction isolated from B. subtilis capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore, (14)C-illudin S taken up by B. subtilis cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis.

  12. Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA) Mode of Action within the Neurodegenerative Pathway: Facts and Controversy

    Science.gov (United States)

    Claudepierre, Thomas; Maignien, Thomas; Arnich, Nathalie

    2017-01-01

    The implication of the cyanotoxin β-N-methylamino-l-alanine (BMAA) in long-lasting neurodegenerative disorders is still a matter of controversy. It has been alleged that chronic ingestion of BMAA through the food chain could be a causative agent of amyotrophic lateral sclerosis (ALS) and several related pathologies including Parkinson syndrome. Both in vitro and in vivo studies of the BMAA mode of action have focused on different molecular targets, demonstrating its toxicity to neuronal cells, especially motoneurons, and linking it to human neurodegenerative diseases. Historically, the hypothesis of BMAA-induced excitotoxicity following the stimulation of glutamate receptors has been established. However, in this paradigm, most studies have shown acute, rather than chronic effects of BMAA. More recently, the interaction of this toxin with neuromelanin, a pigment present in the nervous system, has opened a new research perspective. The issues raised by this toxin are related to its kinetics of action, and its possible incorporation into cellular proteins. It appears that BMAA neurotoxic activity involves different targets through several mechanisms known to favour the development of neurodegenerative processes. PMID:29271898

  13. Mode of action and in vitro susceptibility of mastitis pathogens to macedocin ST91KM and preparation of a teat seal containing the bacteriocin

    Directory of Open Access Journals (Sweden)

    Renee Pieterse

    2010-03-01

    Full Text Available Mastitis is considered to be the most economically costly disease affecting the dairy industry. Regular dosage of animals with antibiotics, including use of prophylactic concentrations, may select for resistant strains. The purpose of this study was to determine the mode of action of a new bacteriocin (macedocin ST91KM, to evaluate the antimicrobial resistance of mastitis pathogens to antibiotics commonly used in treatment remedies, and to introduce the possible use of an alternative antimicrobial agent. The bacteriocin macedocin ST91KM, produced by Streptococcus gallolyticus subsp. macedonicus ST91KM, is bactericidal to Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Staphylococcus aureus associated with mastitis infections, including strains resistant to methicillin and oxacillin. Sensitive cells were deformed and secreted nucleotides, K+ and β-galactosidase when exposed to macedocin ST91KM. Adsorption of the peptide to target cells decreased in the presence of solvents, suggesting that receptors on the cell surfaces have lipid moieties. No adsorption was recorded in the presence of MgCl2, KI and Na2CO3, suggesting that ionic strength plays an important role. A teat seal preparation containing macedocin ST91KM effectively released the peptide and inhibited the growth of S. agalactiae. Macedocin ST91KM could form the basis for alternative dry cow therapy to prevent mastitis infections in dairy cows as it is effective against pathogens that display resistance to conventional antibiotic therapy.

  14. An Amphipathic Undecapeptide with All d-Amino Acids Shows Promising Activity against Colistin-Resistant Strains of Acinetobacter baumannii and a Dual Mode of Action.

    Science.gov (United States)

    Oddo, Alberto; Thomsen, Thomas T; Kjelstrup, Susanne; Gorey, Ciara; Franzyk, Henrik; Frimodt-Møller, Niels; Løbner-Olesen, Anders; Hansen, Paul R

    2015-11-16

    Multiple strains of Acinetobacter baumannii have developed multidrug resistance (MDR), leaving colistin as the only effective treatment. The cecropin-α-melittin hybrid BP100 (KKLFKKILKYL-NH2) and its analogs have previously shown activity against a wide array of plant and human pathogens. In this study, we investigated the in vitro antibacterial activities of 18 BP100 analogs (four known and 14 new) against the MDR A. baumannii strain ATCC BAA-1605, as well as against a number of other clinically relevant human pathogens. Selected peptides were further evaluated against strains of A. baumannii that acquired resistance to colistin due to mutations of the lpxC, lpxD, pmrA, and pmrB genes. The novel analogue BP214 showed antimicrobial activity at 1 to 2 μM and a hemolytic 50% effective concentration (EC50) of >150 μM. The lower activity of its enantiomer suggests a dual, specific and nonspecific mode of action. Interestingly, colistin behaved antagonistically to BP214 when pmrAB and lpxC mutants were challenged. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

    Science.gov (United States)

    Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Kirman, Christopher R.; Harris, Mark A.

    2013-01-01

    Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors. PMID:23445218

  16. Mode of Action Temu Kunci (Kaempferia pandurata Essential Oil on E. coli K1.1 Cell Determined by Leakage of Material Cell and Salt Tolerance Assays

    Directory of Open Access Journals (Sweden)

    MIKSUSANTI

    2008-06-01

    Full Text Available The essential oil of Kaempferia pandurata consist of terpen and oxygenated terpen that exhibits broad-spectrum antimicrobial activity. It's mode of action against the gram-negative bacterium E. coli K1.1 has been investigated using a range of treatments. The mode action of the essential oil were analyzed by it's ability to leakage E. coli K1.1 cell, to change permeability of the cell, and to alter salt tolerance of the cell. Ion leakage from the cell were analyzed by atomic absorption spectrophotometer. Salt tolerance assays was conducted by investigating the ability of E. coli K1.1 treated with temu kunci essential oil to grow on NA supplemented with NaCl. Protein and acid nucleic leakage were analyzed by UV spectrophotometer. There were inorganic compound leakage (potassium, calcium ion and organic compound leakage (nucleic acid, protein from cytoplasmic membrane, after exposing this organism to essential oil of Kaempferia pandurata. The more concentration of oil added, the more leakage was observed due to the loss of absorbing material such as nucleic acid (260 nm and protein (280 nm, the loss of potassium and calcium ion, and loss of the salt tolerance of E. coli K1.1.

  17. Antibacterial Mode of Action of the Essential Oil Obtained from Chamaecyparis obtusa Sawdust on the Membrane Integrity of Selected Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Vivek K. Bajpai

    2014-01-01

    Full Text Available The present study examines the possible antibacterial mechanism of action of the essential oil obtained from Chamaecyparis obtusa (COEO sawdust against foodborne pathogenic bacteria. The COEO was obtained by microwave-assisted hydrodistillation of C. obtusa sawdust. The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC values of COEO against the tested foodborne pathogens including Bacillus cereus ATCC 13061, Listeria monocytogenes ATCC 7644, Staphylococcus aureus ATCC 12600, Salmonella Typhimurium ATCC 43174 and Escherichia coli ATCC 43889 were found in the range from 62.5 to 500 μg/mL and from 125 to 1000 μg/mL, respectively. At the MIC concentrations, the COEO had potential inhibitory effect on the cell viability of the tested bacteria. In addition, the scanning electron microscopic analysis confirmed the inhibitory effect of COEO by revealing significant morphological alterations or rupture of the cell membranes of B. cereus ATCC 13061 and E. coli ATCC 43889. Moreover, the mode of action of COEO on the cell membrane of both Gram-positive B. cereus ATCC 13061 and Gram-negative E. coli ATCC 43889 bacteria was confirmed by marked release of extracellular adenosine 5’-triphosphate (ATP and cellular material that absorbs at 260 nm, and by efflux of potassium ions. These findings suggest that COEO holds a broad-spectrum antibacterial efficacy, confirming its influence on the membrane integrity and morphological characteristics of tested foodborne pathogens.

  18. Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA Mode of Action within the Neurodegenerative Pathway: Facts and Controversy

    Directory of Open Access Journals (Sweden)

    Nicolas Delcourt

    2017-12-01

    Full Text Available The implication of the cyanotoxin β-N-methylamino-l-alanine (BMAA in long-lasting neurodegenerative disorders is still a matter of controversy. It has been alleged that chronic ingestion of BMAA through the food chain could be a causative agent of amyotrophic lateral sclerosis (ALS and several related pathologies including Parkinson syndrome. Both in vitro and in vivo studies of the BMAA mode of action have focused on different molecular targets, demonstrating its toxicity to neuronal cells, especially motoneurons, and linking it to human neurodegenerative diseases. Historically, the hypothesis of BMAA-induced excitotoxicity following the stimulation of glutamate receptors has been established. However, in this paradigm, most studies have shown acute, rather than chronic effects of BMAA. More recently, the interaction of this toxin with neuromelanin, a pigment present in the nervous system, has opened a new research perspective. The issues raised by this toxin are related to its kinetics of action, and its possible incorporation into cellular proteins. It appears that BMAA neurotoxic activity involves different targets through several mechanisms known to favour the development of neurodegenerative processes.

  19. Effect of mitochondrially targeted carboxy proxyl nitroxide on Akt-mediated survival in Daudi cells: Significance of a dual mode of action.

    Directory of Open Access Journals (Sweden)

    Gokul Variar

    Full Text Available Vicious cycles of mutations and reactive oxygen species (ROS generation contribute to cancer progression. The use of antioxidants to inhibit ROS generation promotes cytostasis by affecting the mutation cycle and ROS-dependent survival signaling. However, cancer cells select mutations to elevate ROS albeit maintaining mitochondrial hyperpolarization (Δψm, even under hypoxia. From this perspective, the use of drugs that disrupt both ROS generation and Δψm is a viable anticancer strategy. Hence, we studied the effects of mitochondrially targeted carboxy proxyl nitroxide (Mito-CP and a control ten carbon TPP moiety (Dec-TPP+ in the human Burkitt lymphoma cell line (Daudi and normal peripheral blood mononuclear cells under hypoxia and normoxia. We found preferential localization, Δψm and adenosine triphosphate loss, and significant cytotoxicity by Mito-CP in Daudi cells alone. Interestingly, ROS levels were decreased and maintained in hypoxic and normoxic cancer cells, respectively, by Mito-CP but not Dec-TPP+, therefore preventing any adaptive signaling. Moreover, dual effects on mitochondrial bioenergetics and ROS by Mito-CP curtailed the cancer survival via Akt inhibition, AMPK-HIF-1α activation and promoted apoptosis via increased BCL2-associated X protein and poly (ADP-ribose polymerase expression. This dual mode of action by Mito-CP provides a better explanation of the application of antioxidants with specific relevance to cancerous transformation and adaptations in the Daudi cell line.

  20. Sources and modes of action of invasive knotweed allelopathy: the effects of leaf litter and trained soil on the germination and growth of native plants

    Directory of Open Access Journals (Sweden)

    Madalin Parepa

    2012-05-01

    Full Text Available Invasive knotweeds, native to Eastern Asia, are among the most dominant plant invaders of European and North American temperate ecosystems. Recent studies indicate that one cause of this dominance might be allelopathy, but the possible sources and modes of action of this allelopathy are insufficiently understood. Here, we asked whether the invasive knotweed Fallopia × bohemica can exert allelopathic effects on native plants also through its leaf litter, or through persistent soil contaminants, and whether these affect the germination or growth of native plants. In a germination experiment with nine native species neither litter leachate, an aqueous extract of knotweed leaves added to the soil, nor trained soil with a history of Fallopia pre-cultivation suppressed the germination or early growth of natives. A mesocosm study with experimental native communities showed that the presence of F. × bohemica, although not a dominant in these communities, caused significant shifts of life-history strategy in two dominant natives, and that similar effects could be elicited through litter leachates or trained soil alone. However, there were hardly any effects on the biomass of natives. Our study indicates that knotweed allelopathy acts on the growth rather than germination of natives, and that soil contamination through persistent allelochemicals may not be a significant problem in habitat restoration. It also shows that allelopathic effects can sometimes be subtle changes in life-history and allocation patterns of the affected species.

  1. Mode of action of RNase BN/RNase Z on tRNA precursors: RNase BN does not remove the CCA sequence from tRNA.

    Science.gov (United States)

    Dutta, Tanmay; Deutscher, Murray P

    2010-07-23

    RNase BN, the Escherichia coli homolog of RNase Z, was previously shown to act as both a distributive exoribonuclease and an endoribonuclease on model RNA substrates and to be inhibited by the presence of a 3'-terminal CCA sequence. Here, we examined the mode of action of RNase BN on bacteriophage and bacterial tRNA precursors, particularly in light of a recent report suggesting that RNase BN removes CCA sequences (Takaku, H., and Nashimoto, M. (2008) Genes Cells 13, 1087-1097). We show that purified RNase BN can process both CCA-less and CCA-containing tRNA precursors. On CCA-less precursors, RNase BN cleaved endonucleolytically after the discriminator nucleotide to allow subsequent CCA addition. On CCA-containing precursors, RNase BN acted as either an exoribonuclease or endoribonuclease depending on the nature of the added divalent cation. Addition of Co(2+) resulted in higher activity and predominantly exoribonucleolytic activity, whereas in the presence of Mg(2+), RNase BN was primarily an endoribonuclease. In no case was any evidence obtained for removal of the CCA sequence. Certain tRNA precursors were extremely poor substrates under any conditions tested. These findings provide important information on the ability of RNase BN to process tRNA precursors and help explain the known physiological properties of this enzyme. In addition, they call into question the removal of CCA sequences by RNase BN.

  2. IARC use of oxidative stress as key mode of action characteristic for facilitating cancer classification: Glyphosate case example illustrating a lack of robustness in interpretative implementation.

    Science.gov (United States)

    Bus, James S

    2017-06-01

    The International Agency for Research on Cancer (IARC) has formulated 10 key characteristics of human carcinogens to incorporate mechanistic data into cancer hazard classifications. The analysis used glyphosate as a case example to examine the robustness of IARC's determination of oxidative stress as "strong" evidence supporting a plausible cancer mechanism in humans. The IARC analysis primarily relied on 14 human/mammalian studies; 19 non-mammalian studies were uninformative of human cancer given the broad spectrum of test species and extensive use of formulations and aquatic testing. The mammalian studies had substantial experimental limitations for informing cancer mechanism including use of: single doses and time points; cytotoxic/toxic test doses; tissues not identified as potential cancer targets; glyphosate formulations or mixtures; technically limited oxidative stress biomarkers. The doses were many orders of magnitude higher than human exposures determined in human biomonitoring studies. The glyphosate case example reveals that the IARC evaluation fell substantially short of "strong" supporting evidence of oxidative stress as a plausible human cancer mechanism, and suggests that other IARC monographs relying on the 10 key characteristics approach should be similarly examined for a lack of robust data integration fundamental to reasonable mode of action evaluations. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Discovery of the aryl heterocyclic amine insecticides: synthesis, insecticidal activity, field results, mode of action and bioavailability of a leading field candidate.

    Science.gov (United States)

    Dent, William H; Pobanz, Mark A; Geng, Chaoxian; Sparks, Thomas C; Watson, Gerald B; Letherer, Theodore J; Beavers, Kenneth W; Young, Cathy D; Adelfinskaya, Yelena A; Ross, Ronald R; Whiteker, Greg; Renga, James

    2017-04-01

    γ-Amino butyric acid (GABA) antagonists are proven targets for control of lepidopteran and other pests. New heterocyclic compounds with high insecticidal activity were discovered using a competitive-intelligence-inspired scaffold-hopping approach to generate analogs of fipronil, a known GABA antagonist. These novel aryl heterocyclic amines (AHAs) displayed broad-spectrum activity on a number of chewing insect pests. Through >370 modifications of the core AHA structure, a 7-pyrazolopyridine lead molecule was found to exhibit much improved activity on a number of insect pests. In field trial studies, its performance was 2-4 times lower than commercial standards and also appeared to be species dependent, with good activity seen for larvae of Spodoptera exigua, but inactivity on larvae of Trichoplusia ni. An extensive investigational biology effort demonstrated that these AHA analogs appear to have multiple modes of action, including GABA receptor antagonism and mitopotential or uncoupler activity. The limited capability in larvae of T. ni to convert the lead molecule to its associated open form correlates with the low toxicity of the lead molecule in this species. This work has provided information that could aid investigations of novel GABA antagonists. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  4. Effects of three pesticides that differ in mode of action on the ecology of small indoor aquatic microcosms; an evaluation of the effects of the insecticide chlorpyrifos, the herbicide atrazine and the fungicide carbendazim

    NARCIS (Netherlands)

    Daam, M.A.; Brink, van den P.J.

    2003-01-01

    In the current study, the usefulness of an eight litre microcosm for the ecological risk assessment of pesticides is examined. Risk assessment studies were performed for three pesticides with different modes of action, viz. an insecticide (chlorpyrifos), fungicide (carbendazim) and herbicide

  5. A quasi-experimental cross-disciplinary evaluation of the impacts of education outside the classroom on pupils’ physical activity, well-being and learning: the TEACHOUT study protocol

    Directory of Open Access Journals (Sweden)

    Glen Nielsen

    2016-10-01

    Full Text Available Abstract Background Education Outside the Classroom (EOTC is a teaching method that aims to promote schoolchildren’s learning, physical activity (PA, social relations, motivation, and well-being. EOTC activities are characterized by teachers using the local environment in their teaching, and involve innovative teaching methods, child-led approaches to problem-solving, experimentation, cooperation, PA, and play. EOTC has become common practice for many teachers in Scandinavia; however, only case studies have evaluated its impacts. The TEACHOUT study aims to evaluate the impacts of EOTC on Danish schoolchildren’s PA, social relations, motivation, well-being, and learning. Methods TEACHOUT is a quasi-experimental, cross-disciplinary study. Sixteen schools participated, containing 19 EOTC school classes and 19 parallel non-EOTC classes, with a total of 834 children aged 9 to 13 years. Measures of the children’s social relations, motivation for school, well-being, and academic performance were collected at the beginning and end of the school year. Data on PA levels were collected over ten-day periods during the school year using accelerometers. The amount and characteristics of the actual EOTC provided in both EOTC and non-EOTC classes were monitored day-to-day throughout the school year, using an online teacher survey platform. The effects of EOTC are mainly analysed by comparing EOTC pupils to non-EOTC (i.e. control pupils based on their scores on the outcome variables (i.e. school performance, well-being, motivation, and social relations at the end of the school year, adjusting for the baseline values (from the beginning of the year. The impacts of EOTC on PA are evaluated by comparing the total as well as context-specific amounts of PA of children participating in EOTC to those of children in their parallel non-EOTC classes. Furthermore, the interdependencies between PA, social relations, well-being, motivation, and learning are explored

  6. A quasi-experimental cross-disciplinary evaluation of the impacts of education outside the classroom on pupils' physical activity, well-being and learning: the TEACHOUT study protocol.

    Science.gov (United States)

    Nielsen, Glen; Mygind, Erik; Bølling, Mads; Otte, Camilla Roed; Schneller, Mikkel Bo; Schipperijn, Jasper; Ejbye-Ernst, Niels; Bentsen, Peter

    2016-10-24

    Education Outside the Classroom (EOTC) is a teaching method that aims to promote schoolchildren's learning, physical activity (PA), social relations, motivation, and well-being. EOTC activities are characterized by teachers using the local environment in their teaching, and involve innovative teaching methods, child-led approaches to problem-solving, experimentation, cooperation, PA, and play. EOTC has become common practice for many teachers in Scandinavia; however, only case studies have evaluated its impacts. The TEACHOUT study aims to evaluate the impacts of EOTC on Danish schoolchildren's PA, social relations, motivation, well-being, and learning. TEACHOUT is a quasi-experimental, cross-disciplinary study. Sixteen schools participated, containing 19 EOTC school classes and 19 parallel non-EOTC classes, with a total of 834 children aged 9 to 13 years. Measures of the children's social relations, motivation for school, well-being, and academic performance were collected at the beginning and end of the school year. Data on PA levels were collected over ten-day periods during the school year using accelerometers. The amount and characteristics of the actual EOTC provided in both EOTC and non-EOTC classes were monitored day-to-day throughout the school year, using an online teacher survey platform. The effects of EOTC are mainly analysed by comparing EOTC pupils to non-EOTC (i.e. control) pupils based on their scores on the outcome variables (i.e. school performance, well-being, motivation, and social relations) at the end of the school year, adjusting for the baseline values (from the beginning of the year). The impacts of EOTC on PA are evaluated by comparing the total as well as context-specific amounts of PA of children participating in EOTC to those of children in their parallel non-EOTC classes. Furthermore, the interdependencies between PA, social relations, well-being, motivation, and learning are explored using path analysis. To help describe and

  7. Insight into the mode of action and selectivity of PBRM, a covalent steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type 1.

    Science.gov (United States)

    Trottier, Alexandre; Maltais, René; Ayan, Diana; Barbeau, Xavier; Roy, Jenny; Perreault, Martin; Poulin, Richard; Lagüe, Patrick; Poirier, Donald

    2017-11-15

    17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM), has recently been described as a non-estrogenic, irreversible inhibitor of 17β-HSD1. However, the mode of action of this inhibitor and its selectivity profile have not yet been elucidated. We assessed PBRM potency via in vitro kinetic measurements. The mechanism of enzyme inactivation was also investigated using interspecies (human, mouse, pig and monkey) comparisons via both in vitro assays and in silico analysis. Mouse and human plasma protein binding of PBRM was determined, whereas its selectivity of action was studied using a wide range of potential off-targets (e.g. GPCR, hERG, CYPs, etc.). The affinity constant (Ki=368nM) and the enzyme inactivation rate (kinact=0.087min-1) values for PBRM were determined with purified 17β-HSD1. PBRM was found to be covalently linked to the enzyme. A long delay period (i.e. 3-5days) is required to recover 17β-HSD1 activity following a pretreatment of breast and placenta cell lines with PBRM. Mechanistic analyses showed important interspecies differences of 17β-HSD1 inhibition which support the importance of inactivation for PBRM effect. Evidences of the potency and selectivity of action presented herein for this first non-estrogenic and steroidal covalent irreversible inhibitor of 17β-HSD1 warrant its further development as a potential drug candidate for estrogen-dependent disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life.

    Science.gov (United States)

    Guedj, Jeremie; Dahari, Harel; Rong, Libin; Sansone, Natasha D; Nettles, Richard E; Cotler, Scott J; Layden, Thomas J; Uprichard, Susan L; Perelson, Alan S

    2013-03-05

    The nonstructural 5A (NS5A) protein is a target for drug development against hepatitis C virus (HCV). Interestingly, the NS5A inhibitor daclatasvir (BMS-790052) caused a decrease in serum HCV RNA levels by about two orders of magnitude within 6 h of administration. However, NS5A has no known enzymatic functions, making it difficult to understand daclatasvir's mode of action (MOA) and to estimate its antiviral effectiveness. Modeling viral kinetics during therapy has provided important insights into the MOA and effectiveness of a variety of anti-HCV agents. Here, we show that understanding the effects of daclatasvir in vivo requires a multiscale model that incorporates drug effects on the HCV intracellular lifecycle, and we validated this approach with in vitro HCV infection experiments. The model predicts that daclatasvir efficiently blocks two distinct stages of the viral lifecycle, namely viral RNA synthesis and virion assembly/secretion with mean effectiveness of 99% and 99.8%, respectively, and yields a more precise estimate of the serum HCV half-life, 45 min, i.e., around four times shorter than previous estimates. Intracellular HCV RNA in HCV-infected cells treated with daclatasvir and the HCV polymerase inhibitor NM107 showed a similar pattern of decline. However, daclatasvir treatment led to an immediate and rapid decline of extracellular HCV titers compared to a delayed (6-9 h) and slower decline with NM107, confirming an effect of daclatasvir on both viral replication and assembly/secretion. The multiscale modeling approach, validated with in vitro kinetic experiments, brings a unique conceptual framework for understanding the mechanism of action of a variety of agents in development for the treatment of HCV.

  9. Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer naphthoquinone plumbagin with enhanced efficacy against resistant cancer cells and a genuine mode of action.

    Science.gov (United States)

    Spoerlein-Guettler, Cornelia; Mahal, Katharina; Schobert, Rainer; Biersack, Bernhard

    2014-09-01

    A series of ferrocene and (arene)ruthenium(II) complexes attached to the naturally occurring anticancer naphthoquinones plumbagin and juglone was tested for efficacy against various cancer cell lines and for alterations in the mode of action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and showed IC50 (72 h) values around 1 μM in growth inhibition assays using 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter cell line, for their substrate character for the P-glycoprotein drug eflux pump via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS levels were significantly increased upon treatment with 1c and 2a. These compounds also showed a greater affinity to linear DNA than plumbagin. While plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives 1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated calcein-AM efflux relative to the clinically established sensitizer verapamil. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Mode of action of human pharmaceuticals in fish: the effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study.

    Science.gov (United States)

    Margiotta-Casaluci, Luigi; Hannah, Robert E; Sumpter, John P

    2013-03-15

    In recent years, a growing number of human pharmaceuticals have been detected in the aquatic environment, generally at low concentrations (sub-ng/L-low μg/L). In most cases, these compounds are characterised by highly specific modes of action, and the evolutionary conservation of drug targets in wildlife species suggests the possibility that pharmaceuticals present in the environment may cause toxicological effects by acting through the same targets as they do in humans. Our research addressed the question of whether or not dutasteride, a pharmaceutical used to treat benign prostatic hyperplasia, may cause adverse effects in a teleost fish, the fathead minnow (Pimephales promelas), by inhibiting the activity of both isoforms of 5α-reductase (5αR), the enzyme that converts testosterone into dihydrotestosterone (DHT). Mammalian pharmacological and toxicological information were used to guide the experimental design and the selection of relevant endpoints, according to the so-called "read-across approach", suggesting that dutasteride may affect male fertility and steroid hormone dynamics. Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 μg/L) on fish reproduction. Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females. However, none of the observed adverse effects occurred at concentrations of exposure lower than 32 μg/L; this, together with the low volume of drug prescribed every year (10.34 kg in the UK in 2011), and the extremely low predicted environmental concentration (0.03 ng/L), suggest that, at present, the potential presence of dutasteride in the environment does not represent a threat to wild fish populations. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The anti-adhesive mode of action of a purified mushroom (Lentinus edodes) extract with anticaries and antigingivitis properties in two oral bacterial phatogens.

    Science.gov (United States)

    Signoretto, Caterina; Marchi, Anna; Bertoncelli, Anna; Burlacchini, Gloria; Papetti, Adele; Pruzzo, Carla; Zaura, Egija; Lingström, Peter; Ofek, Itzhak; Pratten, Jonathan; Spratt, David A; Wilson, Michael; Canepari, Pietro

    2014-02-24

    In previous works we have shown that a low-molecular-mass (LMM) fraction from mushroom (Lentinus edodes) homogenate interferes with binding of Streptococcus mutans to hydroxyapatite and Prevotella intermedia to gingival cells. Additionally, inhibition of biofilm formation of both odonto- and periodonto-pathogenic bacteria and detachment from preformed biofilms have been described for this compound. Further purification of mushroom extract has been recently achieved and a sub-fraction (i.e. # 5) has been identified as containing the majority of the mentioned biological activities. The aim of this study was to characterise the bacterial receptors for the purified mushroom sub-fraction #5 in order to better elucidate the mode of action of this compound when interfering with bacterial adhesion to host surfaces or with bacteria-bacteria interactions in the biofilm state. Candidate bacterial molecules to act as target of this compound were bacterial surface molecules involved in cell adhesion and biofilm formation, and, thus, we have considered cell wall associated proteins (CWPs), teichoic acid (TA) and lipoteichoic acid (LTA) of S. mutans, and outer membrane proteins (OMPs) and lipopolysaccharide (LPS) of P. intermedia. Fifteen S. mutans CWPs and TA were capable of binding sub-fraction #5, while LTA did not. As far as P. intermedia is concerned, we show that five OMPs interact with sub-fraction # 5. Capacity of binding to P. intermedia LPS was also studied but in this case negative results were obtained. Binding sub-fraction # 5 to surface molecules of S. mutans or P. intermedia may result in inactivation of their physiological functions. As a whole, these results indicate, at molecular level, the bacterial surface alterations affecting adhesion and biofim formation. For these antimicrobial properties, the compound may find use in daily oral hygiene.

  12. Toxicity assessment of four insecticides with different modes of action on pupae and adults of Eriopis connexa (Coleoptera: Coccinellidae), a relevant predator of the Neotropical Region.

    Science.gov (United States)

    Fogel, Marilina Noelia; Schneider, Marcela Inés; Rimoldi, Federico; Ladux, Lorena Sabrina; Desneux, Nicolas; Ronco, Alicia Estela

    2016-08-01

    Pesticides can be toxic to nontarget organisms including the natural enemies of agricultural pests, thus reducing the biodiversity of agroecosystems. The lethal and sublethal effects of four insecticides with different modes of action-pyriproxyfen, teflubenzuron, acetamiprid, and cypermethrin-were evaluated on pupae and adults of Eriopis connexa, an effective predator in horticultural crops. Pupal survival was reduced by pyriproxyfen (26 %) and cypermethrin (41 %). Malformations in adults emerged from treated pupae were observed after acetamiprid (82.7 and 100 % for 100 and 200 mg a.i./l, respectively), pyriproxyfen (48.6 %), and cypermethrin (13.3 %) treatments. A longer mean oviposition time was also observed in adults emerged from pupae treated with cypermethrin. Moreover, the latter insecticide as well as teflubenzuron did not reduce reproductive parameters, whereas females emerged from pyriproxyfen-treated pupae were not be able to lay eggs even when females showed large abdomens. Upon exposure of adults, survival was reduced to approximately 90 % by acetamiprid, but no reduction occurred with pyriproxyfen, teflubenzuron, or cypermethrin though the fecundity at fifth oviposition time of the female survivors was reduced. Pyriproxyfen decreased the hatching at all the oviposition times tested, whereas fertility was reduced in the fourth and fifth ovipositions by teflubenzuron and in the first and third ovipositions by cypermethrin. In conclusion, all four insecticides tested exhibited lethal or sublethal effects, or both, on E. connexa. The neurotoxic insecticides were more harmful than the insect-growth regulators, and pupae were more susceptible than adults. The toxicity of insecticides on the conservation of predators in agroecosystems of the Neotropical Region is discussed.

  13. Investigation of the Mode of Action Underlying the Tumorigenic Response Induced in B6C3F1 Mice Exposed Orally to Hexavalent Chromium

    Science.gov (United States)

    Thompson, Chad M.; Proctor, Deborah M.; Haws, Laurie C.; Hébert, Charles D.; Grimes, Sheila D.; Shertzer, Howard G.; Kopec, Anna K.; Hixon, J.Gregory; Zacharewski, Timothy R.; Harris, Mark A.

    2011-01-01

    Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice. To investigate the mode of action (MOA) underlying these tumors, a 90-day drinking water study was conducted using similar exposure conditions as in a previous cancer bioassay, as well as lower (heretofore unexamined) drinking water concentrations. Tissue samples were collected in mice exposed for 7 or 90 days and subjected to histopathological, biochemical, toxicogenomic, and toxicokinetic analyses. Described herein are the results of toxicokinetic, biochemical, and pathological findings. Following 90 days of exposure to 0.3–520 mg/l of sodium dichromate dihydrate (SDD), total chromium concentrations in the duodenum were significantly elevated at ≥ 14 mg/l. At these concentrations, significant decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed. Beginning at 60 mg/l, intestinal lesions were observed including villous cytoplasmic vacuolization. Atrophy, apoptosis, and crypt hyperplasia were evident at ≥ 170 mg/l. Protein carbonyls were elevated at concentrations ≥ 4 mg/l SDD, whereas oxidative DNA damage, as assessed by 8-hydroxydeoxyguanosine, was not increased in any treatment group. Significant decreases in the GSH/GSSG ratio and similar histopathological lesions as observed in the duodenum were also observed in the jejunum following 90 days of exposure. Cytokine levels (e.g., interleukin-1β) were generally depressed or unaltered at the termination of the study. Overall, the data suggest that Cr(VI) in drinking water can induce oxidative stress, villous cytotoxicity, and crypt hyperplasia in the mouse intestine and may underlie the MOA of intestinal carcinogenesis in mice. PMID:21712504

  14. Deciphering the mode of action of a mutant Allium sativum Leaf Agglutinin (mASAL), a potent antifungal protein on Rhizoctonia solani.

    Science.gov (United States)

    Ghosh, Prithwi; Roy, Amit; Hess, Daniel; Ghosh, Anupama; Das, Sampa

    2015-10-26

    Mutant Allium sativum leaf agglutinin (mASAL) is a potent, biosafe, antifungal protein that exhibits fungicidal activity against different phytopathogenic fungi, including Rhizoctonia solani. The effect of mASAL on the morphology of R.solani was monitored primarily by scanning electron and light microscopic techniques. Besides different fluorescent probes were used for monitoring various intracellular changes associated with mASAL treatment like change in mitochondrial membrane potential (MMP), intracellular accumulation of reactive oxygen species (ROS) and induction of programmed cell death (PCD). In addition ligand blot followed by LC-MS/MS analyses were performed to detect the putative interactors of mASAL. Knowledge on the mode of function for any new protein is a prerequisite for its biotechnological application. Detailed morphological analysis of mASAL treated R. solani hyphae using different microscopic techniques revealed a detrimental effect of mASAL on both the cell wall and the plasma membrane. Moreover, exposure to mASAL caused the loss of mitochondrial membrane potential (MMP) and the subsequent intracellular accumulation of reactive oxygen species (ROS) in the target organism. In conjunction with this observation, evidence of the induction of programmed cell death (PCD) was also noted in the mASAL treated R. solani hyphae. Furthermore, we investigated its interacting partners from R. solani. Using ligand blots followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses, we identified different binding partners including Actin, HSP70, ATPase and 14-3-3 protein. Taken together, the present study provides insight into the probable mode of action of the antifungal protein, mASAL on R. solani which could be exploited in future biotechnological applications.

  15. Bacterial ribonuclease binase exerts an intra-cellular anti-viral mode of action targeting viral RNAs in influenza a virus-infected MDCK-II cells.

    Science.gov (United States)

    Shah Mahmud, Raihan; Mostafa, Ahmed; Müller, Christin; Kanrai, Pumaree; Ulyanova, Vera; Sokurenko, Yulia; Dzieciolowski, Julia; Kuznetsova, Irina; Ilinskaya, Olga; Pleschka, Stephan

    2018-01-05

    Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase from Bacillus pumilus. Treatment with binase was shown to improve survival of laboratory animals infected with different RNA viruses. Although binase reduced IAV titer in vitro and in vivo, the mode of action (MOA) of binase against IAV at the molecular level has yet not been studied in depth and remains elusive. To analyze whether binase impairs virus replication by direct interaction with the viral particle we applied a hemagglutination inhibition assay and monitored the integrity of the viral RNA within the virus particle by RT-PCR. Furthermore, we used Western blot and confocal microscopy analysis to study whether binase can internalize into MDCK-II cells. By primer extension we examined the effect of binase on the integrity of viral RNAs within the cells and using a mini-genome system we explored the effect of binase on the viral expression. We show that (i) binase does not to attack IAV particle-protected viral RNA, (ii) internalized binase could be detected within the cytosol of MDCK-II cells and that (iii) binase impairs IAV replication by specifically degrading viral RNA species within the infected MDCK-II cells without obvious effect on cellular mRNAs. Our data provide novel evidence suggesting that binase is a potential anti-viral agent with specific intra-cellular MOA.

  16. Inhibition of spoilage mould conidia by acetic acid and sorbic acid involves different modes of action, requiring modification of the classical weak-acid theory.

    Science.gov (United States)

    Stratford, Malcolm; Plumridge, Andrew; Nebe-von-Caron, Gerhardt; Archer, David B

    2009-11-30

    Fungal spoilage of many foods is prevented by weak-acid preservatives such as sorbic acid or acetic acid. We show that sorbic and acetic acids do not both inhibit cells by lowering of internal pH alone and that the "classical weak-acid theory" must be revised. The "classical weak-acid theory" suggests that all lipophilic acids with identical pK(a) values are equally effective as preservatives, causing inhibition by diffusion of molecular acids into the cell, dissociation, and subsequent acidification of the cytoplasm. Using a number of spoilage fungi from different genera, we have shown that sorbic acid was far more toxic than acetic acid, and no correlation existed between resistance to acetic acid and resistance to sorbic acid. The molar ratio of minimum inhibitory concentrations (MICs) (acetic: sorbic) was 58 for Paecilomyces variotii and 14 for Aspergillus phoenicis. Using flow cytometry on germinating conidia of Aspergillusniger, acetic acid at pH 4.0 caused an immediate decline in the mean cytoplasmic pH (pH(i)) falling from neutrality to approximately pH 4.7 at the MIC (80 mM). Sorbic acid also caused a rapid but far smaller drop in pH(i), at the MIC (4.5 mM); the pH remained above pH 6.3. Over 0-5 mM, a number of other weak acids caused a similar fall in cytoplasmic pH. It was concluded that while acetic acid inhibition of A. niger conidia was due to cytoplasmic acidification, inhibition by sorbic acid was not. A possible membrane-mediated mode of action of sorbic acid is discussed.

  17. FTIR Metabolomic Fingerprint Reveals Different Modes of Action Exerted by Structural Variants of N-Alkyltropinium Bromide Surfactants on Escherichia coli and Listeria innocua Cells

    Science.gov (United States)

    Corte, Laura; Tiecco, Matteo; Roscini, Luca; De Vincenzi, Sergio; Colabella, Claudia; Germani, Raimondo; Tascini, Carlo; Cardinali, Gianluigi

    2015-01-01

    Surfactants are extremely important agents to clean and sanitize various environments. Their biocidal activity is a key factor determined by the interactions between amphiphile structure and the target microbial cells. The object of this study was to analyze the interactions between four structural variants of N-alkyltropinium bromide surfactants with the Gram negative Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological and conductometric methods with a previously described FTIR bioassay were used to assess the metabolomic damage exerted by these compounds. All surfactants tested showed more biocidal activity in L. innocua than in E. coli. N-tetradecyltropinium bromide was the most effective compound against both species, while all the other variants had a reduced efficacy as biocides, mainly against E. coli cells. In general, the most prominent metabolomic response was observed for the constituents of the cell envelope in the fatty acids (W1) and amides (W2) regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions). This response was particularly strong and negative in L. innocua, when cells were challenged by N-tetradecyltropinium bromide, and by the variant with a smaller head and a 12C tail (N-dodecylquinuclidinium bromide). Tail length was critical for microbial inhibition especially when acting against E. coli, maybe due the complex nature of Gram negative cell envelope. Statistical analysis allowed us to correlate the induced mortality with the metabolomic cell response, highlighting two different modes of action. In general, gaining insights in the interactions between fine structural properties of surfactants and the microbial diversity can allow tailoring these compounds for the various operative conditions. PMID:25588017

  18. FTIR metabolomic fingerprint reveals different modes of action exerted by structural variants of N-alkyltropinium bromide surfactants on Escherichia coli and Listeria innocua cells.

    Directory of Open Access Journals (Sweden)

    Laura Corte

    Full Text Available Surfactants are extremely important agents to clean and sanitize various environments. Their biocidal activity is a key factor determined by the interactions between amphiphile structure and the target microbial cells. The object of this study was to analyze the interactions between four structural variants of N-alkyltropinium bromide surfactants with the Gram negative Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological and conductometric methods with a previously described FTIR bioassay were used to assess the metabolomic damage exerted by these compounds. All surfactants tested showed more biocidal activity in L. innocua than in E. coli. N-tetradecyltropinium bromide was the most effective compound against both species, while all the other variants had a reduced efficacy as biocides, mainly against E. coli cells. In general, the most prominent metabolomic response was observed for the constituents of the cell envelope in the fatty acids (W1 and amides (W2 regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions. This response was particularly strong and negative in L. innocua, when cells were challenged by N-tetradecyltropinium bromide, and by the variant with a smaller head and a 12C tail (N-dodecylquinuclidinium bromide. Tail length was critical for microbial inhibition especially when acting against E. coli, maybe due the complex nature of Gram negative cell envelope. Statistical analysis allowed us to correlate the induced mortality with the metabolomic cell response, highlighting two different modes of action. In general, gaining insights in the interactions between fine structural properties of surfactants and the microbial diversity can allow tailoring these compounds for the various operative conditions.

  19. Mode of action of long-term low-dose macrolide therapy for chronic sinusitis in the light of neutrophil recruitment.

    Science.gov (United States)

    Suzuki, Hideaki; Ikeda, Katsuhisa

    2002-03-01

    transcription factors such as nuclear factor-kB and activator protein-1. Further investigation of the mode of action of macrolides at the molecular level would lead to the development of safer and more effective drugs for the treatment of chronic sinusitis. In addition, the possible risk of this therapy such as the occurrence of resistant strains have to be carefully surveyed hereafter.

  20. Cytotoxicity and modes of action of four Cameroonian dietary spices ethno-medically used to treat cancers: Echinops giganteus, Xylopia aethiopica, Imperata cylindrica and Piper capense.

    Science.gov (United States)

    Kuete, Victor; Sandjo, Louis P; Wiench, Benjamin; Efferth, Thomas

    2013-08-26

    Echinops giganteus, Imperata cylindrica, Piper capense and Xylopia aethiopica are four medicinal spices used in Cameroon to treat cancers. The above plants previously displayed cytotoxicity against leukemia CCRF-CEM and CEM/ADR5000 cell lines as well as human pancreatic MiaPaCa-2 cells. The present study aims at emphasizing the study of the cytotoxicity and the modes of action of the above plants on a panel of ten cancer cell lines including various sensitive and drug-resistant phenotypes. The study has been extended to the isolation of the bioactive constituents from Echinops giganteus. The cytotoxicity of the extracts was determined using a resazurin reduction assay, whereas the caspase-Glo assay was used to detect the activation of caspases 3/7, caspase 8 and caspase 9 in cells treated with the four extracts. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells, analysis of mitochondrial membrane potential (MMP) as well as measurement of reactive oxygen species (ROS). The four tested extracts inhibited the proliferation of all tested cancer cell lines including sensitive and drug-resistant phenotypes. Collateral sensitivity of cancer cells to the extract of Echinops giganteus was generally better than to doxorubicin. The recorded IC50 ranges were 3.29 µg/mL [against human knockout clones HCT116 (p53(-/-)) colon cancer cells] to 14.32 µg/mL (against human liver hepatocellular carcinoma HepG2 cells) for the crude extract from Echinops giganteus, 4.17 µg/mL (against breast cancer cells transduced with control vector MDA-MB231 cells) to 19.45 µg/mL (against MDA-MB-231 BCRP cells) for that of Piper capense, 4.11 µg/mL (against leukemia CCRF-CEM cells) to 30.60 µg/mL (against leukemia HL60AR cells) for Xylopia aethiopica, 3.28 µg/mL [against HCT116 (p53(-/-)) cells] to 33.43 µg/mL (against HepG2 cells) for Imperata cylindica and 0.11 µg/mL (against CCRF-CEM cells) to 132.47 µg/mL (against HL60AR cells) for doxorubicin. The four

  1. Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-01-30

    As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting

  2. A trial of cross-disciplinary classes at the university and the high school on the seasonal transition and the seasonal feeling from autumn to winter in East Asia (joint activity of meteorology with Japanese classical literature, music and art)

    Science.gov (United States)

    Kato, K.; Sato, S.; Kato, H.; Akagi, R.; Sueishi, N.; Mori, T.; Nakakura, T.; Irie, I.

    2012-04-01

    There are many steps of the rapid seasonal transitions in East Asia influenced by the seasonal cycle of the Asian monsoon system, resulting in the variety of "seasonal feeling" there. For example, the extremely cold air flowing from the Siberian continent to the Japan Islands is transformed by the huge supply of heat and moisture from the underlying sea (the Japan Sea) in midwinter, which brings the large amount of snowfall in the Japan Sea side of the Japan Islands. However, although the air temperature there is still rather higher from November to early December than in the midwinter, such wintertime weather pattern often appears due to the early development of the Siberian high (however, the precipitation is brought not as in snow but as rain). The intermittent rainfall in such situation due to the shallow cumulus clouds from late autumn to early winter is called the word "Shi-gu-re" in Japanese. It is also well known that the "Shi-gu-re" is often used for expression of the "seasonal feeling" in the Japanese classical literature (especially we can see in the Japanese classic poems called "Wa-Ka"). The present study reports a trial of cross-disciplinary class on the seasonal cycle in East Asia in association with the "seasonal feeling" from autumn to winter, by the joint activity of meteorology with the Japanese classical literature, the music, and the art. Firstly, we will summarize the characteristics of the large-scale climate systems and the daily weather situations from autumn to winter. We will also introduce some examples of the expression of the weather situation found in the Japanese classical poems. Next the outline of the cross-disciplinary classes on such topics at the Faculty of Education, Okayama University, and those at Okayama-Ichinomiya High School and Attached Junior High School of Okayama University will be presented together with the analyses of these practices. We should note that the present trial of the classes might also contribute to

  3. Scaling-up impact in perinatology through systems science: Bridging the collaboration and translational divides in cross-disciplinary research and public policy.

    Science.gov (United States)

    Munar, Wolfgang; Hovmand, Peter S; Fleming, Carrie; Darmstadt, Gary L

    2015-08-01

    Despite progress over the past decade in reducing the global burden of newborn deaths, gaps in the knowledge base persist, and means of translating empirical findings into effective policies and programs that deliver life-saving interventions remain poorly understood. Articles in this issue highlight the relevance of transdisciplinary research in perinatology and calls for increased efforts to translate research into public policy and to integrate interventions into existing primary care delivery systems. Given the complexity and multi-causality of many of the remaining challenges in newborn health, and the effects that social and economic factors have over many newborn conditions, it has further been proposed that integrated, multi-sector public policies are also required. In this article, we discuss the application of systems science methods to advance transdisciplinary research and public policy-making in perinatology. Such approaches to research and public policy have been used to address various global challenges but have rarely been implemented in developing country settings. We propose that they hold great promise to improve not only our understanding of complex perinatology problems but can also help translate research-based insights into effective, multi-pronged solutions that deliver positive, intended effects. Examples of successful transdisciplinary science exist, but successes and failures are context specific, and there are no universal blueprints or formulae to reproduce what works in a specific context into different social system settings. Group model building is a tool, based in the field of System Dynamics, that we have used to facilitate transdisciplinary research and, to a lesser extent, policy formulation in a systematic and replicable way. In this article, we describe how group model building can be used and argue for scaling its use to further the translation of empirical evidence and insights into policy and action that increase maternal

  4. South-to-North, cross-disciplinary training in global health practice: ten years of lessons learned from an infectious disease field course in Jamaica.

    Science.gov (United States)

    Scarlett, Henroy P; Nisbett, Richard A; Stoler, Justin; Bain, Brendan C; Bhatta, Madhav P; Castle, Trevor; Harbertson, Judith; Brodine, Stephanie K; Vermund, Sten H

    2011-09-01

    Global commerce, travel, and emerging and resurging infectious diseases have increased awareness of global health threats and opportunities for collaborative and service learning. We review course materials, knowledge archives, data management archives, and student evaluations for the first 10 years of an intensive summer field course in infectious disease epidemiology and surveillance offered in Jamaica. We have trained 300 students from 28 countries through collaboration between the University of the West Indies and U.S. partner universities. Participants were primarily graduate students in public health, but also included health professionals with terminal degrees, and public health nurses and inspectors. Strong institutional synergies, committed faculty, an emphasis on scientific and cultural competencies, and use of team-based field research projects culminate in a unique training environment that provides participants with career-developing experiences. We share lessons learned over the past decade, and conclude that South-to-North leadership is critical in shaping transdisciplinary, cross-cultural, global health practice.

  5. Implementation of palliative care as a mandatory cross-disciplinary subject (QB13 at the Medical Faculty of the Heinrich-Heine-University Düsseldorf, Germany

    Directory of Open Access Journals (Sweden)

    Schulz, Christian

    2015-02-01

    Full Text Available Background: By means of the revision of the Medical Licensure Act for Physicians (ÄAppO in 2009, undergraduate palliative care education (UPCE was incorporated as a mandatory cross sectional examination subject (QB13 in medical education in Germany. Its implementation still constitutes a major challenge for German medical faculties. There is a discrepancy between limited university resources and limited patient availabilities and high numbers of medical students. Apart from teaching theoretical knowledge and skills, palliative care education is faced with the particular challenge of imparting a professional and adequate attitude towards incurably ill and dying patients and their relatives.Project description: Against this background, an evidence-based longitudinal UPCE curriculum was systematically developed following Kern’s Cycle and partly implemented and evaluated by the students participating in the pilot project. Innovative teaching methods (virtual standardised/simulated patient contacts, e-learning courses, interdisciplinary and interprofessional collaborative teaching, and group sessions for reflective self-development aim at teaching palliative care-related core competencies within the clinical context and on an interdisciplinary and interprofessional basis.Results: After almost five years of development and evaluation, the UPCE curriculum comprises 60 teaching units and is being fully implemented and taught for the first time in the winter semester 2014/15. The previous pilot phases were successfully concluded. To date, the pilot phases (n=26, the subproject “E-learning in palliative care” (n=518 and the blended-learning elective course “Communication with dying patients” (n=12 have been successfully evaluated.Conclusion: All conducted development steps and all developed programmes are available for other palliative care educators (Open Access. The integrated teaching formats and methods (video, e-learning module

  6. Implementation of palliative care as a mandatory cross-disciplinary subject (QB13) at the Medical Faculty of the Heinrich-Heine-University Düsseldorf, Germany.

    Science.gov (United States)

    Schulz, Christian; Wenzel-Meyburg, Ursula; Karger, André; Scherg, Alexandra; In der Schmitten, Jürgen; Trapp, Thorsten; Paling, Andreas; Bakus, Simone; Schatte, Gesa; Rudolf, Eva; Decking, Ulrich; Ritz-Timme, Stephanie; Grünewald, Matthias; Schmitz, Andrea

    2015-01-01

    By means of the revision of the Medical Licensure Act for Physicians (ÄAppO) in 2009, undergraduate palliative care education (UPCE) was incorporated as a mandatory cross sectional examination subject (QB13) in medical education in Germany. Its implementation still constitutes a major challenge for German medical faculties. There is a discrepancy between limited university resources and limited patient availabilities and high numbers of medical students. Apart from teaching theoretical knowledge and skills, palliative care education is faced with the particular challenge of imparting a professional and adequate attitude towards incurably ill and dying patients and their relatives. Against this background, an evidence-based longitudinal UPCE curriculum was systematically developed following Kern's Cycle [1] and partly implemented and evaluated by the students participating in the pilot project. Innovative teaching methods (virtual standardised/simulated patient contacts, e-learning courses, interdisciplinary and interprofessional collaborative teaching, and group sessions for reflective self-development) aim at teaching palliative care-related core competencies within the clinical context and on an interdisciplinary and interprofessional basis. After almost five years of development and evaluation, the UPCE curriculum comprises 60 teaching units and is being fully implemented and taught for the first time in the winter semester 2014/15. The previous pilot phases were successfully concluded. To date, the pilot phases (n=26), the subproject "E-learning in palliative care" (n=518) and the blended-learning elective course "Communication with dying patients" (n=12) have been successfully evaluated. All conducted development steps and all developed programmes are available for other palliative care educators (Open Access). The integrated teaching formats and methods (video, e-learning module, interprofessional education, group sessions for reflexive self-development) and

  7. South-to-North, Cross-Disciplinary Training in Global Health Practice: Ten Years of Lessons Learned from an Infectious Disease Field Course in Jamaica

    Science.gov (United States)

    Scarlett, Henroy P.; Nisbett, Richard A.; Stoler, Justin; Bain, Brendan C.; Bhatta, Madhav P.; Castle, Trevor; Harbertson, Judith; Brodine, Stephanie K.; Vermund, Sten H.

    2011-01-01

    Global commerce, travel, and emerging and resurging infectious diseases have increased awareness of global health threats and opportunities for collaborative and service learning. We review course materials, knowledge archives, data management archives, and student evaluations for the first 10 years of an intensive summer field course in infectious disease epidemiology and surveillance offered in Jamaica. We have trained 300 students from 28 countries through collaboration between the University of the West Indies and U.S. partner universities. Participants were primarily graduate students in public health, but also included health professionals with terminal degrees, and public health nurses and inspectors. Strong institutional synergies, committed faculty, an emphasis on scientific and cultural competencies, and use of team-based field research projects culminate in a unique training environment that provides participants with career-developing experiences. We share lessons learned over the past decade, and conclude that South-to-North leadership is critical in shaping transdisciplinary, cross-cultural, global health practice. PMID:21896794

  8. O fenômeno psicológico como objeto de estudo transdisciplinar The psychological phenomenon as a cross-disciplinary subject of study

    Directory of Open Access Journals (Sweden)

    Antonio Marcos Chaves

    2000-01-01

    Full Text Available Fundamentando-se no pressuposto teórico de que o processo de subjetivação individual ocorre em um ambiente cultural circunscrito, produzido pelas relações sociais dos indivíduos de uma dada sociedade, argumenta-se sobre a intercomplementariedade dos conhecimentos da Sociologia, Antropologia e Psicologia. Contudo, as culturas e as formas de relação social têm uma história. Uma história que esclarece as condições de desenvolvimento dos significados das formas de relação social, econômicas e políticas. Sendo assim, todo contexto cultural, político, social e econômico no qual se constrói a subjetividade individual, para ser compreendido em qualquer dos seus momentos, requer a sua reconstrução histórica.Based on the theoretical assumption that the individual subjectivity process takes place in a restricted cultural context in a given society, we discuss the cross-complementarity of the knowledge from Sociology, Anthropology, and Psychology. However, the cultures and the types of social relationships have a history that illuminates the developmental conditions of the meanings of the types of social, economic, and political relationships. Thus, to understand the whole cultural, political, social, and economic context in which the individual subjectivity is built, its historical reconstruction is required.

  9. Use of the antiozonant ethylenediurea (EDU) in Italy: Verification of the effects of ambient ozone on crop plants and trees and investigation of EDU's mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Paoletti, Elena, E-mail: e.paoletti@ipp.cnr.i [IPP-CNR, Via Madonna del Piano 10, I-50019 Sesto Fiorentino, Florence (Italy); Contran, Nicla [Department of Biotechnology and Biology, University of Milano-Bicocca, Piazza della Scienza 1, Milan (Italy); Manning, William J. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Amherst, MA 01003-9320 (United States); Ferrara, Anna M. [IPLA, Corso Casale 476, I-10128 Turin (Italy)

    2009-05-15

    Twenty-four experiments where EDU was used to protect plants from ozone (O{sub 3}) in Italy are reviewed. Doses of 150 and 450 ppm EDU at 2-3 week intervals were successfully applied to alleviate O{sub 3}-caused visible injury and growth reductions in crop and forest species respectively. EDU was mainly applied as soil drench to crops and by stem injection or infusion into trees. Visible injury was delayed and reduced but not completely. In investigations on mode of action, EDU was quickly (<2 h) uptaken and translocated to the leaf apoplast where it persisted long (>8 days), as it cannot move via phloem. EDU did not enter cells, suggesting it does not directly affect cell metabolism. EDU delayed senescence, did not affect photosynthesis and foliar nitrogen content, and stimulated antioxidant responses to O{sub 3} exposure. Preliminary results suggest developing an effective soil application method for forest trees is warranted. - EDU was successful as a tool in determining ozone effects on vegetation in Italy, but while progress was made, its mode of action remains unresolved.

  10. A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC

    Directory of Open Access Journals (Sweden)

    Ashokkumar A. Patel

    2007-01-01

    Full Text Available Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1 for bioinformatics and a repository of serum and tissue samples; (2 a data model for biomarker data storage; and (3 a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual

  11. Cross-disciplinary, authentic student research projects

    NARCIS (Netherlands)

    Heck, A.; Uylings, P.; Kędzierska, E.; Ellermeijer, T.

    2010-01-01

    In the Dutch secondary education system, students must carry out at the end of their school career a rather large research or design project to demonstrate their ability to apply acquired knowledge and skills while pursuing a research question or design goal in some depth. They are encouraged to

  12. Bacteriocins from Lactobacillus plantarum production, genetic organization and mode of action: produção, organização genética e modo de ação Bacteriocinas de Lactobacillus plantarum

    Directory of Open Access Journals (Sweden)

    Svetoslav D. Todorov

    2009-06-01

    Full Text Available Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented.Bacteriocinas são proteínas ou complexos protéicos biologicamente ativos que apresentam atividade bactericida contra espécies relacionadas. Nas ultimas duas décadas, várias cepas de Lactobacillus plantarum produtoras de bacteriocinas foram isoladas de diferentes nichos ecológicos como carnes, peixes, frutas, vegetais e produtos lácteos e de cereais. Várias plantaricinas foram caracterizadas e suas seqüências de aminoácidos determinadas. Diferentes aspectos do modo de ação, otimização da fermentação e organização genética já foram estudados. Entretanto, muitas bacteriocinas produzidas por diferentes cepas de Lactobacillus plantarum ainda não foram completamente caracterizadas.Nesse artigo, apresenta-se uma breve revisão sobre a classificação, genética, caracterização, modo de ação, e otimização da produção de bacteriocinas de bactérias láticas em geral, e, quando apropriado, de bacteriocinas de Lactobacillus plantarum.

  13. Integrating transcriptomics and metabonomics to unravel modes-of-action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells

    NARCIS (Netherlands)

    Jennen, D.G.J.; Ruiz-Aracama, A.; Magkoufopoulou, C.; Peijnenburg, A.A.C.M.; Lommen, A.; Delft, van J.; Kleinjans, J.C.S.

    2011-01-01

    Background The integration of different 'omics' technologies has already been shown in several in vivo studies to offer a complementary insight into cellular responses to toxic challenges. Being interested in developing in vitro cellular models as alternative to animal-based toxicity assays, we

  14. A peripherally restricted P2Y12 receptor antagonist altered rat tumor incidences with no human relevance: Mode of action consistent with dopamine agonism

    Directory of Open Access Journals (Sweden)

    David A. Brott

    2014-01-01

    Discussion: Similar to Ticagrelor, centrally active dopamine agonists induce the same altered tumor incidence patterns that according to literature do not translate into the clinical setting, with a MOA involving decreased prolactin secretion. The Ticagrelor MOA data and literature suggest that altered dopamine levels in the hypophyseal part of the hypothalamus–hypophyseal axis (by Ticagrelor will result in similar altered tumor incidences in rat that do not translate into the clinical setting, based on qualitative species differences. In conclusion Ticagrelor increased uterine tumors in the rat carcinogenesis study by a MOA consistent with reduced dopamine inhibition of prolactin, which is not a patient safety risk.

  15. First insights into the mode of action of a "lachrymatory factor synthase"--implications for the mechanism of lachrymator formation in Petiveria alliacea, Allium cepa and Nectaroscordum species.

    Science.gov (United States)

    He, Quan; Kubec, Roman; Jadhav, Abhijit P; Musah, Rabi A

    2011-11-01

    A study of an enzyme that reacts with the sulfenic acid produced by the alliinase in Petiveria alliacea L. (Phytolaccaceae) to yield the P. alliacea lachrymator (phenylmethanethial S-oxide) showed the protein to be a dehydrogenase. It functions by abstracting hydride from sulfenic acids of appropriate structure to form their corresponding sulfines. Successful hydride abstraction is dependent upon the presence of a benzyl group on the sulfur to stabilize the intermediate formed on abstraction of hydride. This dehydrogenase activity contrasts with that of the lachrymatory factor synthase (LFS) found in onion, which catalyzes the rearrangement of 1-propenesulfenic acid to (Z)-propanethial S-oxide, the onion lachrymator. Based on the type of reaction it catalyzes, the onion LFS should be classified as an isomerase and would be called a "sulfenic acid isomerase", whereas the P. alliacea LFS would be termed a "sulfenic acid dehydrogenase". Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Baseline Susceptibility of Filarial Vector Culex quinquefasciatus (Diptera: Cu-licidae to Five Insecticides with Different Modes of Action in Southeast of Iran

    Directory of Open Access Journals (Sweden)

    Yaser Salim-Abadi

    2017-12-01

    Full Text Available Background: Culex quinquefasciatus (Diptera: Culicidae is an important vector for many human diseases. The aim of this study was to evaluate the susceptibility level of larval and adult stages of Cu. quinquefasciatus to different groups of WHO recommended insecticides for vector control.Methods: Larval stages of the Culex mosquitoes were collected from their natural habitats in Rafsanjan County at Kerman Province, southeast of Iran in 2016. Insecticide susceptibility status of adult female Cx. quinquefasciatus against DDT (4%, deltamethrin (0.05%, malathion 5%, and bendiocarb (0.1% were determined using WHO stand­ard insecticide susceptibility test. Additional test was carried out to determine the susceptibility status of larvae of Cx. quinquefasciatus to temephos. Bioassay data were analyzed by Probit program.Results: Cx. quinquefasciatus adults showed resistance to all four groups of the tested insecticides according to the WHO criteria for resistance evaluation. The lethal concentrations for 50% mortality (LC50 and 90% mortality (LC90 of temephos against Cx. quinquefasciatus larvae were 0.18mg/l and 0.78mg/l, respectively. This finding also con­firms resistance to temephos based on the WHO recommended instructions for resistance evaluation.Conclusion: Resistance to all groups of the tested insecticides should be considered for future vector control investi­gations in the study area.

  17. Purification, Characterization, and Mode of Action of Pentocin JL-1, a Novel Bacteriocin Isolated from Lactobacillus pentosus, against Drug-Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Han Jiang

    2017-01-01

    Full Text Available Staphylococcus aureus and its drug-resistant strains, which threaten public health and food safety, are in need of effective control by biopreservatives. A novel bacteriocin, pentocin JL-1, produced by Lactobacillus pentosus that was isolated from the intestinal tract of Chiloscyllium punctatum, was purified by a four-step chromatographic process. Mass spectrometry based on MALDI-TOF indicated that pentocin JL-1 has a molecular mass of 2987.23 Da. Only six of the twenty-five amino acids could be identified by Edman degradation. This bacteriocin is thermostable and tolerates a pH range of 5–7. Also, it is sensitive to proteinase K, trypsin, pepsin, and alkaline protease. This bacteriocin has a broad inhibitory spectrum against both Gram-positive and Gram-negative strains and in particular is effective against multidrug-resistant S. aureus. Additionally, we showed that the cell membrane is the target of pentocin JL-1 against methicillin-resistant S. aureus (MRSA, causing a loss of proton motive force. Furthermore, pentocin JL-1 has a drastic impact on the structure and integrity of MRSA cells. These results suggest that pentocin JL-1 has potential as a biopreservative in the food industry.

  18. Determination of the modes of action and synergies of xylanases by analysis of xylooligosaccharide profiles over time using fluorescence-assisted carbohydrate electrophoresis.

    Science.gov (United States)

    Gong, Weili; Zhang, Huaiqiang; Tian, Li; Liu, Shijia; Wu, Xiuyun; Li, Fuli; Wang, Lushan

    2016-07-01

    The structure of xylan, which has a 1,4-linked β-xylose backbone with various substituents, is much more heterogeneous and complex than that of cellulose. Because of this, complete degradation of xylan needs a large number of enzymes that includes GH10, GH11, and GH3 family xylanases together with auxiliary enzymes. Fluorescence-assisted carbohydrate electrophoresis (FACE) is able to accurately differentiate unsubstituted and substituted xylooligosaccharides (XOS) in the heterogeneous products generated by different xylanases and allows changes in concentrations of specific XOS to be analyzed quantitatively. Based on a quantitative analysis of XOS profiles over time using FACE, we have demonstrated that GH10 and GH11 family xylanases immediately degrade xylan into sizeable XOS, which are converted into smaller XOS in a much lower speed. The shortest substituted XOS produced by hydrolysis of the substituted xylan backbone by GH10 and GH11 family xylanases were MeGlcA(2) Xyl3 and MeGlcA(2) Xyl4 , respectively. The unsubstituted xylan backbone was degraded into xylose, xylobiose, and xylotriose by both GH10 and GH11 family xylanases; the product profiles are not family-specific but, instead, depend on different subsite binding affinities in the active sites of individual enzymes. Synergystic action between xylanases and β-xylosidase degraded MeGlcA(2) Xyl4 into xylose and MeGlcA(2) Xyl3 but further degradation of MeGlcA(2) Xyl3 required additional enzymes. Synergy between xylanases and β-xylosidase was also found to significantly accelerate the conversion of XOS into xylose. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Pharmacodynamic studies on the central mode of action of S-adenosyl-L-methionine (SAMe) infusions in elderly subjects, utilizing EEG mapping and psychometry.

    Science.gov (United States)

    Saletu, B; Anderer, P; Linzmayer, L; Semlitsch, H V; Lindeck-Pozza, E; Assandri, A; di Padova, C; Saletu-Zyhlarz, G M

    2002-12-01

    In a double-blind, placebo-controlled cross-over study, the acute and subacute effects of S-adenosyl-L-methionine (SAMe), or ademetionine, on brain function and behavior of 10 elderly normal healthy volunteers (5 males and 5 females, aged 56-71 years, mean: 59.3 years) were investigated by means of EEG mapping and psychometry. In random order they received infusions of 800 mg SAMe and placebo, administered over 30 minutes for 7 days, with a wash-out period of 3 weeks in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 hours after drug administration on days 1 and 7. Multivariate analysis based on MANOVA/Hotelling T(2) tests demonstrated significant central effects of SAMe as compared with placebo after acute, subacute and superimposed drug administration. Acute SAMe-induced changes were characterized by a decrease in total power, an increase in absolute delta and a decrease in absolute alpha power, further by an increase in relative delta and a decrease in relative alpha power, a slowing of the delta/theta centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. After one week of daily infusions there was a marked increase in total power, reminiscent of nootropic drug effects. One additional superimposed dosage mitigated these effects in the direction of an antidepressant profile, with the inter-drug differences waning in the 6(th) hour. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects underlying the antidepressant properties of SAMe well-documented in clinical trials. Psychometric tests concerning noopsychic and thymopsychic measures as well as critical flicker frequency generally demonstrated a lack of differences between SAMe and placebo, which again reflects a good tolerability of the drug in elderly subjects.

  20. Mortality in dioxin-exposed mice infected with influenza: mitochondrial toxicity (reye's-like syndrome) versus enhanced inflammation as the mode of action.

    Science.gov (United States)

    Luebke, Robert W; Copeland, Carey B; Bishop, Lisa R; Daniels, Mary J; Gilmour, M Ian

    2002-09-01

    Increased mortality following influenza A infection was reported in B6C3F1 mice exposed to a low (0.01 micro g/kg) dose of dioxin. However, mortality was not associated with increased viral load and antibody titers to the virus were not decreased at doses of TCDD Reye's syndrome (RS) in humans, is responsible for increased mortality in dioxin-exposed, infected B6C3F1 female mice, based on similarities in the biochemical and immunological events that occur in RS and in TCDD-exposed animals. Endpoints were also included to test the hypothesis that increased pulmonary inflammation following dioxin exposure, in the absence of mitochondrial toxicity, was associated with increased mortality. Dose-related effects of TCDD alone, infection with influenza A alone, and combined TCDD exposure/influenza infection were evaluated. Mice were given a single ip injection of 0, 0.001, 0.01, 0.1, or 1.0 micro g TCDD/kg, 7 days before infection by intranasal instillation of an estimated LD(10-20) of influenza A Hong Kong/8/68 (H3N2) and were terminated 1, 7, and 10 days after infection. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for various measurements, including clinical chemistries, cell counts, cytokine analysis, and viral titers. Exposure to < or = 1.0 micro g TCDD/kg did not increase mortality; virus titers were similar at all doses of TCDD and there was no dioxin-related effect on serum NH(3) or glucose concentrations, two prominent indicators of the altered mitochondrial oxidative metabolism typically observed in RS. A study was therefore conducted over a wider range of TCDD doses. A single injection of 0, 0.025, 0.5, or 10 micro g TCDD/kg preceded infection by 7 days; subgroups of noninfected control and highest dose group (10 micro g TCDD/kg) mice were also evaluated for biochemical and immunological endpoints on the equivalent of infection day 4 to provide baseline data. Five days after infection the same endpoints described above were

  1. mode of action (Part 2 of 4)

    African Journals Online (AJOL)

    Production of anti-microbial substances. One of the most important mechanisms though which probiotic bacteria exert their effects on pathogens invading the human body, is the production of a range of compounds with strong anti- microbial properties. During fermentation, lactic acid bacteria produce a range of short-chain.

  2. Mode of Action of Illudin S

    Science.gov (United States)

    Walser, J.; Heinstein, P. F.

    1973-01-01

    The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from Escherichia coli pol A1−, with E. coli DNA-dependent RNA polymerase, with E. coli pol A1− spheroplasts, and with frozen and thawed Bacillus subtilis cells. A protein fraction isolated from B. subtilis capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore, 14C-illudin S taken up by B. subtilis cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis. PMID:4208286

  3. Lactococcins : Mode of action, immunity and secretion

    NARCIS (Netherlands)

    Venema, K; Kok, J; Venema, Gerhardus

    1995-01-01

    Lactococcus lactis subsp. cremoris 9B4 produces three small (around 5kDa), heat-stable, non-lanthionine containing, membrane active bacteriocins. Amino acid uptake experiments and proton motive force measurements have indicated that these peptides most probably form pores in the cytoplasmic membrane

  4. Azelaic acid: Properties and mode of action.

    Science.gov (United States)

    Sieber, M A; Hegel, J K E

    2014-01-01

    Acne is a common skin disorder that can be problematic for adults as well as for adolescents. It has several key pathophysiological features such as follicular hyperkeratosis, elevated Propionibacterium acnes proliferation, and reactive inflammation, all of which should be targeted for an optimal outcome. Azelaic acid (AzA) has profound anti-inflammatory, antioxidative effects, and is bactericidal against a range of Gram-negative and Gram-positive microorganisms as well, including antibiotic-resistant bacterial strains. In addition, AzA's antikeratinizing effects are inhibitory toward comedones. AzA is effective overall in targeting multiple causes of acne and has been proven to be well tolerated in numerous clinical trials. © 2013 S. Karger AG, Basel.

  5. Deciphering Mode of Action of Functionally Important Regions in the Intrinsically Disordered Paxillin (Residues 1-313 Using Its Interaction with FAT (Focal Adhesion Targeting Domain of Focal Adhesion Kinase.

    Directory of Open Access Journals (Sweden)

    Muniasamy Neerathilingam

    Full Text Available Intrinsically disordered proteins (IDPs play a major role in various cellular functions ranging from transcription to cell migration. Mutations/modifications in such IDPs are shown to be associated with various diseases. Current strategies to study the mode of action and regulatory mechanisms of disordered proteins at the structural level are time consuming and challenging. Therefore, using simple and swift strategies for identifying functionally important regions in unstructured segments and understanding their underlying mechanisms is critical for many applications. Here we propose a simple strategy that employs dissection of human paxillin (residues 1-313 that comprises intrinsically disordered regions, followed by its interaction study using FAT (Focal adhesion targeting domain of focal adhesion kinase as its binding partner to retrace structural behavior. Our findings show that the paxillin interaction with FAT exhibits a masking and unmasking effect by a putative intra-molecular regulatory region. This phenomenon suggests how cancer associated mutations in paxillin affect its interactions with Focal Adhesion Kinase (FAK. The strategy could be used to decipher the mode of regulations and identify functionally relevant constructs for other studies.

  6. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

  7. Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

    Science.gov (United States)

    Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

    2016-06-01

    The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

  8. Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: Evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna, E-mail: anna@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Hagiwara, Akihiro; Imai, Norio [DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113 (Japan); Nagano, Kasuke [Nagano Toxicologic-Pathology Consulting, Ochiai, Hadano, Kanagawa 257-0025 (Japan); Nishimaki, Fukumi [Biofuel Assessment Group, New Fuels Dept., Japan Petroleum Energy Center (JPEC), 4-3-9 Toranomon, Minato-ku, Tokyo 105-0001 (Japan); Banton, Marcy [Toxicology and Risk Assessment, LyondellBasell Industries, LyondellBasell Corporate HSE/Product Safety, One Houston Center, Suite 700, 1221 McKinney Street, Houston, TX 770 10 (United States); Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0011 (Japan); Wanibuchi, Hideki [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2013-12-01

    To elucidate possible mode of action (MOA) and human relevance of hepatotumorigenicity in rats for ethyl tertiary-butyl ether (ETBE), male F344 rats were administered ETBE at doses of 0, 150 and 1000 mg/kg body weight twice a day by gavage for 1 and 2 weeks. For comparison, non-genotoxic carcinogen phenobarbital (PB) was applied at a dose of 500 ppm in diet. Significant increase of P450 total content and hydroxyl radical levels by low, high doses of ETBE and PB treatments at weeks 1 and 2, and 8-OHdG formation at week 2, accompanied accumulation of CYP2B1/2B2, CYP3A1/3A2 and CYP2C6, and downregulation of DNA oxoguanine glycosylase 1, induction of apoptosis and cell cycle arrest in hepatocytes, respectively. Up-regulation of CYP2E1 and CYP1A1 at weeks 1 and 2, and peroxisome proliferation at week 2 were found in high dose ETBE group. Results of proteome analysis predicted activation of upstream regulators of gene expression altered by ETBE including constitutive androstane receptor (CAR), pregnane-X-receptor (PXR) and peroxisome proliferator-activated receptors (PPARs). These results indicate that the MOA of ETBE hepatotumorigenicity in rats may be related to induction of oxidative stress, 8-OHdG formation, subsequent cell cycle arrest, and apoptosis, suggesting regenerative cell proliferation after week 2, predominantly via activation of CAR and PXR nuclear receptors by a mechanism similar to that of PB, and differentially by activation of PPARs. The MOA for ETBE hepatotumorigenicity in rats is unlikely to be relevant to humans. - Highlights: • We focus on MOA and human relevance of hepatotumorigenicity in rats for ETBE. • ETBE was administered to F344 rats for 1 and 2 weeks. • Oxidative stress formation, proliferation and apoptosis in the liver are analyzed. • ETBE-induced changes of gene and protein expression in the liver are examined. • The effects are compared with those induced by non-genotoxic carcinogen PB.

  9. Rule Based Expert System for Cerebral Palsy Diagnosis

    OpenAIRE

    Borgohain, Rajdeep; Sanyal, Sugata

    2012-01-01

    The use of Artificial Intelligence is finding prominence not only in core computer areas, but also in cross disciplinary areas including medical diagnosis. In this paper, we present a rule based Expert System used in diagnosis of Cerebral Palsy. The expert system takes user input and depending on the symptoms of the patient, diagnoses if the patient is suffering from Cerebral Palsy. The Expert System also classifies the Cerebral Palsy as mild, moderate or severe based on the presented symptoms.

  10. A quasi-experimental cross-disciplinary evaluation of the impacts of education outside the classroom on pupils’ physical activity, well-being and learning: the TEACHOUT study protocol

    DEFF Research Database (Denmark)

    Nielsen, Glen; Mygind, Erik; Bølling, Mads

    2016-01-01

    Background: Education Outside the Classroom (EOTC) is a teaching method that aims to promote schoolchildren’s learning, physical activity (PA), social relations, motivation, and well-being. EOTC activities are characterized by teachers using the local environment in their teaching, and involve...... innovative teaching methods, child-led approaches to problem-solving, experimentation, cooperation, PA, and play. EOTC has become common practice for many teachers in Scandinavia; however, only case studies have evaluated its impacts. The TEACHOUT study aims to evaluate the impacts of EOTC on Danish...... in both EOTC and nonEOTC classes were monitored day-to-day throughout the school year, using an online teacher survey platform. The effects of EOTC are mainly analysed by comparing EOTC pupils to non-EOTC (i.e. control) pupils based on their scores on the outcome variables (i.e. school performance, well...

  11. Modelling in cross-disciplinary authentic student research projects

    NARCIS (Netherlands)

    Heck, A.

    2010-01-01

    In the Dutch secondary education system, students must carry out at the end of their school career a rather large research or design project to demonstrate their ability to apply acquired knowledge and skills while pursuing a research question or design goal in some depth. They are encouraged to

  12. A Semantic Approach to Cross-Disciplinary Research Collaboration

    Directory of Open Access Journals (Sweden)

    Laurens De Vocht

    2012-11-01

    Full Text Available The latest developments in ICT, more specifically Social Media and Web 2.0 tools, facilitate the use of online services in research and education. This is also known as Research 2.0 and Technology Enhanced Learning. Web 2.0 tools are especially useful in cases where experts from different disciplines want to collaborate. We suggest an integrated method that embeds these services in research and learning processes, because it is a laborious task for researchers and learners to check and use all varying types of tools and services. We explain a flexible model that uses state-of-the-art semantic technologies to model both structured and unstructured research data. The research data is extracted from many online resources and Social Media. We implement learning objects as an abstraction of the semantically modeled research data. We propose an environment that improves the scientific research and learning process by allowing researchers to efficiently browse the information and concepts represented as learning objects.

  13. [Implementing the Cross-Disciplinary Subject Palliative Care - Lecture's Perspective].

    Science.gov (United States)

    Isermeyer, Leonie; Ilse, Benjamin; Marx, Gabriella; Seidemann, Stephanie; Jünger, Jana; Nauck, Friedemann; Alt-Epping, Bernd

    2017-11-01

    Introduction  In 2009, palliative care was introduced as a mandatory subject in the undergraduate medical curriculum in Germany. Despite all efforts to integrate this subject into the curriculum, research suggests substantial differences and deficits in the quality of education between the medical schools. The aim of this research was to find out promoting as well as impedimental aspects of implementing palliative care in the medical training program. By this, a suitable framework in terms of content and structure for palliative care teaching should be extracted. Methods  We performed guided interviews with 15 of the in total 36 lecturers responsible for the implementation of palliative care teaching at their respective medical schools. We focused on content, design and methods of implementation within the palliative care curriculum. Data was evaluated by content analysis according to Meuser and Nagel. Results  We found that a lack of recognition of this subject within the medical faculties, coupled with entrenched structures of an already packed syllabus, were considered to be most relevant for the given heterogeneity in the implementation process. Deficits in personnel, financial and time resources also contributed to the perceived deficits. Faced with these difficulties, inner- and cross-faculty teamwork and support, extracurricular activities as well as external funds have proven to be important resources. Discussion  To promote the implementation process, medical faculties need established palliative care structures that meet the interests and needs of the students more effectively. Analysis of structural needs (for instance, the amount of apprenticeships and teachings units) would be an important step to prove political claims. Moreover, the development of suitable and resource-saving teaching and assessment methods should be promoted. © Georg Thieme Verlag KG Stuttgart · New York.

  14. How University Teachers Design Assessments: A Cross-Disciplinary Study

    Science.gov (United States)

    Bearman, Margaret; Dawson, Phillip; Bennett, Sue; Hall, Matt; Molloy, Elizabeth; Boud, David; Joughin, Gordon

    2017-01-01

    There are dissonances between educators' aspirations for assessment design and actual assessment implementation in higher education. Understanding how assessment is designed "on the ground" can assist in resolving this tension. Thirty-three Australian university educators from a mix of disciplines and institutions were interviewed. A…

  15. How university teachers design assessments: a cross disciplinary study

    OpenAIRE

    Bearman, Margaret; Dawson, Phillip; Bennett, Sue; Hall, Matt; Molloy, Elizabeth; Boud, David; Joughin, Gordon

    2017-01-01

    There are dissonances between educators’ aspirations for assessment design and actual assessment implementation in higher education. Understanding how assessment is designed ‘on the ground’ can assist in resolving this tension. Thirty-three Australian university educators from a mix of disciplines and institutions were interviewed. A thematic analysis of the transcripts indicated that assessment design begins as a response to an impetus for change. The design process itself was shaped by envi...

  16. CIDER: a cross-disciplinary institute with educational mission

    Science.gov (United States)

    Dziewonski, A.; Romanowicz, B.

    2003-04-01

    CIDER (Cooperative Institute for Deep Earth Research) is an emerging initiative within the solid Earth community in the US, designed to remedy the lack of satisfactory communication and cooperation among the geoscience fields dealing with the Earth's deep interior, defined here as anything between the crust and the Earth's center. It has been 35 years since the acceptance of plate tectonics theory, but no definitive agreement has yet been reached among geoscientists on the fundamental nature of the global dynamic processes that drive plate motions. There are still vigorous debates about the proportion of heat coming from the core, vs. radiogenic heating in the mantle, about the degree to which the 670 km discontinuity impedes whole mantle circulation, about the origin of mantle plumes, or the chemical or thermal nature of heterogeneity in the deepest mantle. The principal mission of Cider is to provide a long-range intellectual framework that will allow a more effective cross-fertilization of the different disciplines, whereby senior and junior scientists alike can be thoroughly educated about the approaches, the fundamental achievements, the future potential and limitations of the "other disciplines", in order to gain a common language. Given the enormous amount and diversity of observations becoming available across the relevant disciplines, a quantum leap in the understanding of our planet's interior - the constitution and evolution of the Earth - is about to take place if we can better understand the key issues and how to address them by fully utilizing complementary disciplinary data and modeling tools. This will be accomplished through a series of short and long courses, workshops, and interdisciplinary research programs focused on a specific topic. A related goal is to attract to geophysics more talented and better prepared graduate students.

  17. A Cross-Disciplinary Examination of Print Resources on Abortion

    Science.gov (United States)

    Johnson, Wendell G.

    2011-01-01

    Abortion is a highly-charged, emotional topic which often appears in the news, particularly during the confirmation process for a Supreme Court nominee. Community College students continue to ask reference librarians for print resources dealing with this controversial issue. Often we turn to the reliable series "Current Controversies," "At Issue,"…

  18. Modelling in Cross-Disciplinary Authentic Student Research Projects

    Science.gov (United States)

    Heck, Andre

    2010-01-01

    In the Dutch secondary education system, students must carry out at the end of their school career a research or design project to demonstrate their ability to apply acquired knowledge and skills while pursuing a rather large research question or design goal in some depth. They are encouraged to choose the topic themselves and they are to some…

  19. Cross-disciplinary academic partnership produces new materials journal

    OpenAIRE

    Nystrom, Lynn A.

    2005-01-01

    Virginia Tech's staff of the Journal of Undergraduate Materials Research (JUMR), a journal created for undergraduate student research in materials science and engineering, has published the "Alfred Knobler Inaugural Issue" and presented it to the Virginia Tech Materials Science and Engineering Advisory Board.

  20. Cross-Disciplinary Ethics Education in MBA Programs

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich; Schedel, Ingo

    : business schools increasingly risk creating a gap between their upbeat rhetoric around ethics education and their actual MBA curriculum. Such decoupling is likely to emerge because schools face a tension between increasing institutional pressures to legitimize their MBA programs and internal impediments...

  1. Cross-Disciplinary Ethics Education in MBA Programs

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich; Schedel, Ingo

    2013-01-01

    : business schools increasingly risk creating a gap between their upbeat rhetoric around ethics education and their actual MBA curriculum. Such decoupling is likely to emerge because schools face a tension between increasing institutional pressures to legitimize their MBA programs and internal impediments...

  2. Cross-Disciplinary Scientific Foundation for Sustainability: Qualitative Economics

    DEFF Research Database (Denmark)

    Fast, Alf Michael; Clark, Woodrow

    2017-01-01

    We need to understand everyday interactions as “qualitative economics” as they have their roots in the historical, subjectivist, and philosophical tradition. As a starting point, we use the philosophy of science perspective and analysis. As the 21st century moves rapidly into a new economic era...

  3. Stress among healthcare students--a cross disciplinary perspective.

    Science.gov (United States)

    Jacob, Tamar; Itzchak, Esther Ben; Raz, Olga

    2013-07-01

    Perceived stress (PS) among healthcare students worldwide is a recognized problem. To address the paucity of data about the actual degree of PS, this study aimed to: 1) evaluate and compare PS across three healthcare programs (Physical Therapy [PT], Communication Disorders [CD], and Nutrition Sciences [NS]) in one university; 2) evaluate changes in PS across study years; 3) identify the contribution of academic- and socio-demographic-related variables to PS; and 4) determine whether the Israeli students' PS levels differ from those of their peers in other countries. A cross-sectional survey was performed among all undergraduate PT, CD, and NS students from one university. Data were collected using anonymous questionnaires. Instruments included the Perceived Stress Scale 10 (PSS) and the Undergraduate Sources of Stress (USOS). ANOVA was used to evaluate the differences between the three programs, and regression analysis to evaluate the contribution of socio-demographic factors to PS and USOS. A total of 312 students (PT--154; CD--92; NS--66) participated in the study. Mean PSS (range: 13.5-13.6) was similar in the three programs. The USOS academic factor was the most reported source of stress in all programs. Most socio-demographic variables were not related to either PS or USOS. Students from PT, CD, and NS programs perceived similar levels of stress. The academic factor was perceived as the most important source of stress by students from the three departments, despite differences in the academic educational programs. Further studies are needed to generalize these results and enable a comparison between healthcare students and other students' stress perceptions.

  4. EUDAT: A New Cross-Disciplinary Data Infrastructure For Science

    Science.gov (United States)

    Lecarpentier, Damien; Michelini, Alberto; Wittenburg, Peter

    2013-04-01

    In recent years significant investments have been made by the European Commission and European member states to create a pan-European e-Infrastructure supporting multiple research communities. As a result, a European e-Infrastructure ecosystem is currently taking shape, with communication networks, distributed grids and HPC facilities providing European researchers from all fields with state-of-the-art instruments and services that support the deployment of new research facilities on a pan-European level. However, the accelerated proliferation of data - newly available from powerful new scientific instruments, simulations and the digitization of existing resources - has created a new impetus for increasing efforts and investments in order to tackle the specific challenges of data management, and to ensure a coherent approach to research data access and preservation. EUDAT is a pan-European initiative that started in October 2011 and which aims to help overcome these challenges by laying out the foundations of a Collaborative Data Infrastructure (CDI) in which centres offering community-specific support services to their users could rely on a set of common data services shared between different research communities. Although research communities from different disciplines have different ambitions and approaches - particularly with respect to data organization and content - they also share many basic service requirements. This commonality makes it possible for EUDAT to establish common data services, designed to support multiple research communities, as part of this CDI. During the first year, EUDAT has been reviewing the approaches and requirements of a first subset of communities from linguistics (CLARIN), solid earth sciences (EPOS), climate sciences (ENES), environmental sciences (LIFEWATCH), and biological and medical sciences (VPH), and shortlisted four generic services to be deployed as shared services on the EUDAT infrastructure. These services are data replication from site to site, data staging to compute facilities, metadata, and easy storage. A number of enabling services such as distributed authentication and authorization, persistent identifiers, hosting of services, workspaces and centre registry were also discussed. The services being designed in EUDAT will thus be of interest to a broad range of communities that lack their own robust data infrastructures, or that are simply looking for additional storage and/or computing capacities to better access, use, re-use, and preserve their data. The first pilots were completed in 2012 and a pre-production ready operational infrastructure, comprised of five sites (RZG, CINECA, SARA, CSC, FZJ), offering 480TB of online storage and 4PB of near-line (tape) storage, initially serving four user communities (ENES, EPOS, CLARIN, VPH) was established. These services shall be available to all communities in a production environment by 2014. Although EUDAT has initially focused on a subset of research communities, it aims to engage with other communities interested in adapting their solutions or contributing to the design of the infrastructure. Discussions with other research communities - belonging to the fields of environmental sciences, biomedical science, physics, social sciences and humanities - have already begun and are following a pattern similar to the one we adopted with the initial communities. The next step will consist of integrating representatives from these communities into the existing pilots and task forces so as to include them in the process of designing the services and, ultimately, shaping the future CDI.

  5. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action

    DEFF Research Database (Denmark)

    Lehmann, Anders; Antonsson, Madeleine; Holmberg, Ann Aurell

    2009-01-01

    brain; AZD3355, but not baclofen, was concentrated in circumventricular organs as a result of active uptake (shown by avid intracellular sequestration) and related to binding of AZD3355 to native GABA transporters in rat cerebrocortical membranes. AZD3355 was also shown to be transported by all four......Gastroesophageal reflux disease (GERD) affects >10% of the Western population. Conventionally, GERD is treated by reducing gastric acid secretion, which is effective in most patients but inadequate in a significant minority. We describe a new therapeutic approach for GERD, based on inhibition...... recombinant human GABA transporters. AR-H061719 [(R/S)-(3-amino-2-fluoropropyl)phosphinic acid], (the racemate of AZD3355) inhibited the response of ferret mechanoreceptors to gastric distension, further supporting its peripheral site of action on TLESR. In summary, AZD3355 probably inhibits TLESR through...

  6. Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action.

    Science.gov (United States)

    Sun, Ning; Du, Ruo-Lan; Zheng, Yuan-Yuan; Huang, Bao-Hua; Guo, Qi; Zhang, Rui-Fang; Wong, Kwok-Yin; Lu, Yu-Jing

    2017-07-28

    The emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Targeting at the inhibition of bacterial cell division via the control of FtsZ function is one of the effective and promising approaches. Some natural extracts from plants such as sanguinarine and berberine (analogs of pyridinium compounds) are known to alter FtsZ function. In this study, a series of novel quaternary pyridinium compounds was constructed based on the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and their antibacterial activity against nine significant pathogens was investigated using broth microdilution method. In the in vitro assay, the compounds showed strong antibacterial activities against various testing strains, which include some drug-resistant strains such as methicillin-resistant S. aureus and vancomycin-resistant E. faecium. Our results of morphology change of B. subtilis cells and molecular docking proved that the compounds functioned as an effective inhibitor to suppress FtsZ polymerization and FtsZ GTPase activity and thus the compound stops cell division and cause cell death through interacting with C-terminal interdomain cleft of FtsZ. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

    Directory of Open Access Journals (Sweden)

    Sheeja Aravindan

    Full Text Available Pancreatic cancer (PC remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27. Total anti-oxidant capacity (TAC analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.

  8. Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

    Science.gov (United States)

    Aravindan, Sheeja; Delma, Caroline R; Thirugnanasambandan, Somasundaram S; Herman, Terence S; Aravindan, Natarajan

    2013-01-01

    Pancreatic cancer (PC) remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27). Total anti-oxidant capacity (TAC) analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol) identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent) inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation) in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.

  9. Anti-Pancreatic Cancer Deliverables from Sea: First-Hand Evidence on the Efficacy, Molecular Targets and Mode of Action for Multifarious Polyphenols from Five Different Brown-Algae

    Science.gov (United States)

    Aravindan, Sheeja; Delma, Caroline R.; Thirugnanasambandan, Somasundaram S.; Herman, Terence S.; Aravindan, Natarajan

    2013-01-01

    Pancreatic cancer (PC) remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27). Total anti-oxidant capacity (TAC) analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol) identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent) inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation) in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process. PMID:23613993

  10. Mode of Action of Insecticides Used in Vector Management

    OpenAIRE

    DURMUŞOĞLU, Enver

    2015-01-01

    Since it was understood that many of the diseases which caused mass human deaths are carried by vectors, their management has become increasingly important. The fact that humans are living in larger settlements with large populations, the improvements in international commerce and transportation and also the increase of the traveled distance as well as the frequency of human travels have had an important part in this matter. On the other hand, as in other cases while the increase of knowledge...

  11. Ecdysone Agonist: New Insecticides with Novel Mode of Action

    Directory of Open Access Journals (Sweden)

    Y. Andi Trisyono

    2002-12-01

    Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

  12. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

    Directory of Open Access Journals (Sweden)

    Shiyao Jiang

    2017-02-01

    Full Text Available Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  13. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

    OpenAIRE

    Shiyao Jiang; Maia Tsikolia; Bernier, Ulrich R.; Bloomquist, Jeffrey R.

    2017-01-01

    Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal do...

  14. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

    Science.gov (United States)

    Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R; Bloomquist, Jeffrey R

    2017-02-06

    Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  15. Antimicrobial peptides (AMPs): peptide structure and mode of action.

    Science.gov (United States)

    Park, Yoonkyung; Hahm, Kyung-Soo

    2005-09-30

    Antimicrobial peptides (AMPs) have been isolated and characterized from tissues and organisms representing virtually every kingdom and phylum. Their amino acid composition, amphipathicity, cationic charge, and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of AMP activity, their relevance to resolving how peptides damage and kill microorganisms still needs to be clarified. Moreover, many AMPs employ sophisticated and dynamic mechanisms of action to carry out their likely roles in antimicrobial host defense. Recently, it has been speculated that transmembrane pore formation is not the only mechanism of microbial killing by AMPs. In fact, several observations suggest that translocated AMPs can alter cytoplasmic membrane septum formation, reduce cell-wall, nucleic acid, and protein synthesis, and inhibit enzymatic activity. In this review, we present the structures of several AMPs as well as models of how AMPs induce pore formation. AMPs have received special attention as a possible alternative way to combat antibiotic-resistant bacterial strains. It may be possible to design synthetic AMPs with enhanced activity for microbial cells, especially those with antibiotic resistance, as well as synergistic effects with conventional antibiotic agents that lack cytotoxic or hemolytic activity.

  16. Mode of Action and Synergy of Ceftazidime and Baicalein against ...

    African Journals Online (AJOL)

    Purpose: To investigate the antibacterial activity of baicalein used alone, or in combination with ceftazidime, against Streptococcus pyogenes. Methods: Minimum inhibitory concentration (MIC), checkerboard assay parameters, and viability curves were determined for S. pyogenes DMST 30653, 30654, and 30655.

  17. Mode of Action and Synergy of Ceftazidime and Baicalein against ...

    African Journals Online (AJOL)

    Cytoplasmic membrane (CM) permeability technique, enzyme assays, transmission electron microscopy and Fourier transforminfrared microspectroscopy were used to investigate the changes in the bacterial biomolecules. Results: The MIC of ceftazidime and baicalein against all the S. pyogenes strains were 0.50 and ...

  18. Artemisinin inhibits chloroplast electron transport activity: mode of action.

    Directory of Open Access Journals (Sweden)

    Adyasha Bharati

    Full Text Available Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo, behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.

  19. Mode of action of lipoic acid in diabetes

    Indian Academy of Sciences (India)

    Administrator

    effect of these changes in the key enzymic activities is seen in the increased rates of oxidation of glucose and a reduction in fatty acid oxidation in diabetes following lipoic acid admini- stration. Keywords. Lipoic acid; diabetes; Coenzyme A; pyruvate dehydrogenase; lipid biosynthesis; acetoacetate metabolism. Introduction.

  20. Antimicrobial activity of GN peptides and their mode of action

    DEFF Research Database (Denmark)

    Godballe, Troels; Mojsoska, Biljana; Nielsen, Hanne M

    2015-01-01

    and the observed anti-bacterial and cytotoxic activity for this set of peptides. In conjunction, these findings provide strong indications of membrane disruption as the primary mechanism of bacterial growth inhibition for the tested peptides. This article is protected by copyright. All rights reserved....... peptides due to their characteristics as naturally derived compounds with antimicrobial activity. In this study we aimed at characterizing the mechanism of action of a small set of in silico optimized peptides. Following determination of peptide activity against E. coli, S. aureus and P. aeruginosa...... demonstrated bacterial membrane disruption after 10 minutes for the most active peptides. The membrane disrupting effect was verified by measuring the release of calcein from bacterial mimicking liposomes. This revealed the most active peptides as inducers of immediate release, indicating the kinetics...

  1. Neurotoxicological effects and the mode of action of pyrethroid insecticides

    NARCIS (Netherlands)

    Vijverberg, H.P.M.; Bercken, Joep van den

    1990-01-01

    Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system. Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and

  2. On the antifungal mode of action of tridemorph

    NARCIS (Netherlands)

    Kerkenaar, A.; Barug, D.; Kaars Sijpesteijn, A.

    1979-01-01

    Tridemorph (2,6-dimethyl-N-tridecylmorpholine) was active against representative of nearly all taxonomic groups of fungi; gram-positive bacteria were also sensitive although gram-negative were not. Tridemorph, 3–10 μg/ml, inhibited the multiplication of sporidia of Ustilago maydis more strongly than

  3. Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antibacterial effect of ethanol extract of Mentha arvensis against multi-drug resistant Acinetobacter baumannii using liquid chromatography–mass spectrometry (LC-ESI-MS). Methods: Disc diffusion and microdilution assays were used to evaluate the antibacterial effect of the extract by measuring ...

  4. Antibiotic growth promoters in agriculture: history and mode of action.

    Science.gov (United States)

    Dibner, J J; Richards, J D

    2005-04-01

    This report will review the history of antibiotic growth promoter (AGP) use in the animal industry, concerns about development of antimicrobial resistance, and response in the European Union and United States to these concerns. A brief description of the history of legislation regarding feed use of antimicrobials in Denmark and the experience of animal producers following the 1998 ban will serve to illustrate the consequences on animal performance and health of withdrawing the approval for this use. The biological basis for antibiotic effects on animal growth efficiency will consider effects on intestinal microbiota and effects on the host animal and will use the germ-free animal to illustrate effects of the conventional microflora. The probability that no single compound will replace all of the functions of antimicrobial growth promoters will be considered, and methods to consolidate and analyze the enlarging database will be discussed.

  5. Mode of action of plant defensins suggests therapeutic potential

    NARCIS (Netherlands)

    Thomma, B.P.H.J.; Cammue, B.P.A.; Thevissen, K.

    2003-01-01

    Higher vertebrates can rely both on an innate as well as an adaptive immune system for defense against invading pathogens. In contrast, plants can only employ an innate immune system that largely depends on the production of antimicrobial compounds such as plant defensins and other

  6. Catechin as an antimutagen: its mode of action.

    Science.gov (United States)

    Nagabhushan, M; Maru, G B; Amonkar, A J; Nair, U J; Santhanam, U; Ammigan, N; D'Souza, A V; Bhide, S V

    1988-01-01

    In the present study, we report that the betel quid ingredient catechu, its extract and pure principle catechin were nonmutagenic in Salmonella typhimurium TA 100, TA 1535, TA 98, and TA 1538 assays with or without metabolic activation. They also exhibited dose-dependent decreases in mutagenicity of benzo(a)pyrene [B(a)P] and dimethylbenz(a)anthracene (DMBA) in strain TA 98 with metabolic activation. We further report that these compounds inhibited activities of cytochrome P-450 and had no effect on glutathione-S-transferase but increased the glutathione content in rat liver tissue. Simultaneous treatment of catechin prevented the mutagenic activity of B(a)P and DMBA metabolites in strain TA 98 in the absence of metabolic activation. Pre- and post-treatment of bacteria with catechin had no effect on the mutagenicity of B(a)P and DMBA metabolites. Catechin also inhibited the in vitro binding of 3H-B(a)P metabolites to calf thymus DNA. Catechu extract and catechin inhibited the nitrosation of methylurea by nitrite at pH 3.6 and 30 degrees C. The formation of nitrosomethylurea in the reaction mixture was monitored by measuring the histidine revertants of strain TA 1535 in the absence of metabolic activation. Pre- and post-treatment of catechu extract or catechin had no effect on the mutagenicity of nitrosomethylurea in TA 1535. The nitrosation inhibition by catechin was through scavenging of nitrite observed at pH 3.6. The above study indicates that catechu in betel quid may act as an antimutagen and may suppress the mutagenic potential of other betel quid mutagens.

  7. Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index ..... the Medical Science and Technology Innovation. Fund of ...

  8. Mode of action of anticancer peptides (ACPs) from amphibian origin.

    Science.gov (United States)

    Oelkrug, Christopher; Hartke, Martin; Schubert, Andreas

    2015-02-01

    Although cancer belongs to one of the leading causes of death around the world, fortunately studies have shown that tumor cells have various targets that are susceptible to attack. Interestingly, tumor cells are comprised of cellular membranes, which are altered in chemical composition relative to non-neoplastic cells, giving them an increased net negative charge. These altered membranes are ideal targets for antimicrobial peptides (AMPs) shown to have additional tumoricidal properties and, hence, named anticancer peptides (ACPs). Several hundred ACPs have been explored in vitro and in vivo on various types of cancer. Novel anticancer agents are supposed not to cause serious side effects and the formation of multidrug-resistant tumor cells. During the quest for potent ACPs, promising candidates were isolated from skin secretions of amphibians, such as the granular glands of the Chinese brown frog, Rana chensinensis. ACPs have to be selective to cancer cells and should not induce strong immune responses or be cleared from the body rapidly. Several modifications can improve ACPs either by optimizing the primary structure rationally or randomly or even by introducing other chemical modifications. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Synthesis and mode of action of oligomeric sesquiterpene lactones.

    Science.gov (United States)

    Li, Chao; Jones, Alexander X; Lei, Xiaoguang

    2016-05-04

    Covering: up to 2015In this highlight we describe two case studies from our laboratory, involving the biomimetic syntheses and the biological mechanism elucidation of the bioactive oligomeric sesquiterpenoids, (+)-ainsliadimer A () and (-)-ainsliatrimer A (). Ainsliadimer A possesses potent anti-inflammatory activity by inhibition of the NF-κB signalling pathway via binding at a previously untargeted allosteric site. (-)-Ainsliatrimer A induces apoptosis in cancer cells by activation of PPARγ. Furthermore, we highlight a new bioorthogonal ligation (TQ-ligation) developed in our laboratory which facilitates the target identification of complex natural products via pre-target fluorescence imaging and affinity chromatography. Generally, this paper will discuss the complete process from total synthesis to biological studies of complex natural products, and from the establishment of new bio-orthogonal chemistry to successful target identification. Our approach provides a systematic and efficient methodology for addressing the challenge of natural product target identification.

  10. Mode of action of aspirin as a chemopreventive agent.

    Science.gov (United States)

    Dovizio, Melania; Bruno, Annalisa; Tacconelli, Stefania; Patrignani, Paola

    2013-01-01

    Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.

  11. The structure and mode of action of the dinoflagellate toxins

    Directory of Open Access Journals (Sweden)

    Akram Najafi

    2016-07-01

    Full Text Available Background: Dinoflagellates are the major causative agents of harmful algal blooms. In different studies, it has been shown that many dinoflagellate species produce various natural toxins. Saxitoxin, brevetoxin, yessotoxin, etc can be considered as the most important neurotoxins. The most important dinoflagellate toxins structures, their origin, structure and mechanisms of action were evaluated in a systematic review. Materials & Methods: Marine dinoflagellates, marine toxins, and their mechanisms of action and structure were keywords for a comprehensive search in online databases including Pubmed, Science Direct, Google Scholar and Scirus. A total of 95 papers were evaluated, however, by omitting similar reports, 68 papers were included in the study. Results: Dinoflagellates toxins are usually polycyclic ether and polyketaide compounds that have distinct mechanisms of action including alteration in different ion channels and/or pumps at cell membrane, effect on the normal functioning of neuronal and other excitable tissues, inhibition of serine/threonine phosphoprotein phosphatases, disrupting major mechanisms of controlling cellular functions, and alteration in cellular cytoskeleton. However, the precise mechanisms of action of few toxins are not determined yet. Conclusion: The clarification of the dinoflagellate toxins structures and their mechanisms of action may be helpful for novel drug design, therapeutic measures and to overcome against marine toxicity. 

  12. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  13. Efeito e modo de ação das bacteriocinas produzidas por Lactococcus lactis subsp. lactis ITAL 383, ATCC 11454 e CNRZ 150 contra Listeria innocua LIN 11 Effect and mode of action of the bacterioncin produced by Lactococcus. lactis subsp. lactis ITAL 383, ATCC 11454 e CNRZ 150 against Listeria innocua LIN 11

    Directory of Open Access Journals (Sweden)

    Izildinha MORENO

    1999-01-01

    Full Text Available O efeito e o modo de ação das bacteriocinas produzidas por L. lactis subsp. lactis ITAL 383 e CNRZ 150 são similares à nisina de L. lactis subsp. lactis ATCC 11454. Estas bacteriocinas apresentaram um modo de ação bactericida, causando a lise de células de L. innocua LIN 11, associada ao decréscimo da absorbância e da viabilidade celular. O efeito letal foi maior para células em fase exponencial comparativamente à fase estacionária de crescimento. A adsorção dessas bacteriocinas às células de L. innocua LIN 11 foi muito rápida e influenciada pelo pH do meio de suspensão; adsorção máxima foi verificada a pH 6,0 e logo após o contato inicial. Perda completa de adsorção ocorreu em pH 2,0.The effect and mode of action of the bacteriocin produced by L. lactis subsp. lactis ITAL 383 and CNRZ 150 are similar to the nisin produced by L. lactis subsp. lactis ATCC 11454. It was clearly bactericidal, and caused lysis of a strain of L. innocua LIN 11 detected by the decrease of absorbance values and the cell viability. Their lethal effect was considerably higher during the logarithmic growth when compared to the stationary phase. Adsorption developed rapidly and was influenced by the pH value of the suspension medium. Maximum adsorption was observed at pH 6,0 and immediately after initial contact and loss at pH 2,0.

  14. Lewis acid-Lewis base catalyzed enantioselective hetero-Diels-Alder reaction for direct access to delta-lactones.

    Science.gov (United States)

    Tiseni, Paolo S; Peters, René

    2008-05-15

    A complex formed in situ from Er(OTf)3 and a simple commercially available norephedrine ligand promotes an unprecedented [4 + 2] cycloaddition of alpha,beta-unsaturated acid chlorides with a broad range of aromatic and heteroaromatic aldehydes by a cooperative bifunctional Lewis acid-Lewis base catalytic mode of action providing valuable delta-lactone building blocks with excellent enantioselectivity.

  15. Analytical perspectives on performance-based management

    DEFF Research Database (Denmark)

    Wadmann, Sarah; Johansen, Sarah; Lind, Ane

    2013-01-01

    Performance-based management (PBM) has become a dominant form of governance in health care and there is a need for careful assessment of its function and effects. This article contains a cross-disciplinary literature synthesis of current studies of PBM. Literature was retrieved by database search...... perspectives allows appreciation of otherwise implicit assumptions and potential implications of PBM. Reflections on such differences are important to ensure vigilant appropriation of shifting management tools in health quality governance.......Performance-based management (PBM) has become a dominant form of governance in health care and there is a need for careful assessment of its function and effects. This article contains a cross-disciplinary literature synthesis of current studies of PBM. Literature was retrieved by database searches....... In the functionalist perspective, PBM is perceived as a management tool aimed at improving health care services by means of market-based mechanisms. In the interpretive perspective, the adoption of PBM is understood as consequence of institutional and individual agents striving for public legitimacy. In the post...

  16. Early design interference detection based on qualitative physics

    NARCIS (Netherlands)

    D'Amelio, V.; Chmarra, M.K.; Tomiyama, T.

    2011-01-01

    Developing multi-disciplinary products presents cross-disciplinary problems that are difficult to predict and to solve. Unfortunately, those cross-disciplinary problems are often discovered only at a later stage of the design through physical prototypes and can lead to modification of the conceptual

  17. Academic Globalization: Universality of Cross-Cultural And Cross-Disciplinary LMR Perspectives

    Directory of Open Access Journals (Sweden)

    Marta Szabo White

    2010-10-01

    Full Text Available The contribution of this paper suggests that previous research underscoring cross-cultural differences may be misleading, when in fact it is cross-professional rather than cross-cultural differences that should be emphasized. Employing the LMR framework, this paper concludes that business or non-business predisposition has a more direct impact on one's individual cultural profile than does nationality. Regardless of culture, persons involved in business are characterized primarily by linear-active modes of communication, and persons not involved in business typically employ less linear and more multi-active/hybrid modes of communication. The linkages among individual characteristics, communication styles, work behaviors, and the extent to which the LMR constructs can facilitate and predict leadership, negotiating styles, individual behaviors, etc. are central to academic globalization and preparing global business leaders.

  18. Enhancing Students' Interest in Science and Technology through Cross-Disciplinary Collaboration and Active Learning Techniques

    Science.gov (United States)

    Grant, Donna M.; Malloy, Alisha D.; Hollowell, Gail P.

    2013-01-01

    Twenty-nine rising high school 12th grade students participated in a 4-week summer program designed to increase their interest in science and technology. The program was a blend of hands-on biology, chemistry, and technology modules that addressed the global issue of obesity. Student groups developed websites to address obesity in one of five…

  19. Uniqueness of family therapists as family business systems consultants: a cross-disciplinary investigation.

    Science.gov (United States)

    Lee, Jinhee; Danes, Sharon M

    2012-06-01

    The purpose of this study is to address how the consulting approaches of family therapists working with family businesses differ from those of business consultants. The logic of analytic induction was used to analyze qualitative data from family business consultants with and without training in family therapy. Consultants were asked to respond to two vignettes: one emphasized primarily family system problems, whereas the other emphasized business problems with influencing issues at the family/business intersection. Both similarities and differences were found in reference to problem assessment, consulting goal orientation, intervention strategy focus, consultant role and function, and consulting setting preference between consultants with and without family therapy training. Results indicate that consultants of each discipline provide a unique perspective and expertise that allow them to successfully address the spectrum of issues that family firms face. Further, findings highlight the unique contribution of family therapists to an interdisciplinary consulting team. © 2012 American Association for Marriage and Family Therapy.

  20. Proofs and Persuasion: A Cross-Disciplinary Analysis of Math Students' Writing

    Science.gov (United States)

    Bahls, Patrick; Mecklenburg-Faenger, Amy; Scott-Copses, Meg; Warnick, Chris

    2011-01-01

    This article offers an initial analysis of the rhetorical devices used by mathematics undergraduates as they begin to write research articles in their discipline. The authors (a mathematician and three experts in composition and rhetoric) identify several such devices, including transitions and metacommentary, style and tone, use of sources, and…

  1. A Cross-Disciplinary Approach to Teaching Data Literacy and Proportionality

    Science.gov (United States)

    Vahey, Philip; Rafanan, Ken; Patton, Charles; Swan, Karen; van't Hooft, Mark; Kratcoski, Annette; Stanford, Tina

    2012-01-01

    The Thinking with Data project (TWD) expands on current notions of data literacy by (1) focusing on proportional reasoning as key to data literacy and (2) leveraging the non-mathematics disciplines to engage students in deep thinking about the context of data and the application of proportionality. A set of four 2-week, sequential modules for…

  2. A Multi- and Cross-Disciplinary Capstone Experience in Engineering Art: Animatronic Polar Bear

    Science.gov (United States)

    Sirinterlikci, Arif; Toukonen, Kayne; Mason, Steve; Madison, Russel

    2005-01-01

    An animatronic robot was designed and constructed for the 2003 Annual Student Robotic Technology and Engineering Challenge organized by the Robotics International (RI) association of the Society of Manufacturing Engineers (SME). It was also the senior capstone design project for two of the design team members. After a thorough study of body and…

  3. Incommensurability in Cross-Disciplinary Research: A Call for Cultural Negotiation

    Directory of Open Access Journals (Sweden)

    Anne MacCleave

    2006-06-01

    Full Text Available What happens when a clinical psychologist, a grounded theorist, an ethnographer, and a phenomenologist meet to collaborate on an interdisciplinary grant proposal on childhood loneliness? Excerpts of an imaginary dialogue reveal how different disciplines can be thought of as different “cultures,” because each has its own way of doing things, deeply embedded assumptions about knowledge and the construction/representation of reality, and different specialized languages. Some of these differences might be incommensurable and call for cultural negotiation if a coherent approach is to be adopted. Cultural negotiation helps to make differences more accessible and understandable rather than creating inflexible or polarized ideological camps. This process might help methodologists think about researching across disciplines in new and more effective ways.

  4. Cross-Disciplinary Collaboration: Fostering Professional Communication Skills in a Graduate Accounting Certificate Program

    Science.gov (United States)

    Brizee, Allen; Langmead, Joseph

    2014-01-01

    For decades, scholars and working professionals have known that accountants struggle with communication. Experts agree that integrating communication pedagogy into accounting courses is the most effective way of addressing this problem, but an integrated approach is not always possible. In this programmatic and pedagogical article, we address this…

  5. Monitoring glacier change: advances in cross-disciplinary research and data sharing methods

    Science.gov (United States)

    Arendt, A. A.; O'Neel, S.; Cogley, G.; Hill, D. F.; Hood, E. W.

    2016-12-01

    Recent studies have emphasized the importance of understanding interactions between glacier change and downstream ecosystems, ocean dynamics and human infrastructure. Despite the need for integrated assessments, few in-situ and remote sensing glacier monitoring studies also collect concurrent data on surrounding systems affected by glacier change. In addition, the sharing of glacier datasets across disciplines has often been hampered by limitations in data sharing technologies and a lack of data standardization. Here we provide an overview of recent efforts to facilitate distribution of glacier inventory/change datasets under the framework provided by the Global Terrestrial Network for Glaciers (GTN-G). New, web accessible data products include glacier thickness data and updated glacier extents from the Randolph Glacier Inventory. We also highlight a 2016 data collection effort led by the US Geological Survey on the Wolverine Glacier watershed, Alaska, USA. A large international team collected glaciological, water quality, snow cover, firn composition, vegetation and freshwater ecology data, using remote sensing/in-situ data and model simulations. We summarize preliminary results and outline our use of cloud-computing technologies to coordinate the integration of complex data types across multiple research teams.

  6. Toward the Building of a Cross-Disciplinary Doctoral Research and Writing Culture

    Science.gov (United States)

    Johnson, E. Marcia

    2014-01-01

    Within the New Zealand university context, there has been a dramatic shift in the demographics of doctoral programs. Moving from an elitist educational environment to one that includes a variety of students from different cultures and educational and linguistic backgrounds has meant that "traditional" doctoral study, in which a student…

  7. Getting Queer: Teacher Education, Gender Studies, and the Cross-Disciplinary Quest for Queer Pedagogies

    Science.gov (United States)

    Whitlock, Reta Ugena

    2010-01-01

    Contextualized through the lens of place, this essay explores intersections and tensions among queer theory, teacher education, and identities/identifications, which looks to the author like a particular way of looking at curriculum, pedagogy, and the self. Since the three general concepts are intertwined and irreducible, the author's particular…

  8. Final Commentary to the Cross-Disciplinary Thematic Special Series: Special Education and Mathematics Education

    Science.gov (United States)

    Woodward, John; Tzur, Ron

    2017-01-01

    Four studies into characteristics and instructional needs of students with learning disabilities are summarized in this article. These studies are also reviewed in the wider context of mathematics intervention research in special education. These studies generally rely on qualitative methodology, and they are best understood in light of a…

  9. Social technologies : Cross-disciplinary reflections on technologies in and from the social sciences Introduction

    NARCIS (Netherlands)

    Derksen, Maarten; Vikkelso, Signe; Beaulieu, Anne

    In this introduction, we explore the relevance to critical psychology of the ideas about technology that have come from science and technology studies (STS), which we argue allow a new look at a classic theme in critical approaches in psychology. Rather than seeing psychical and social reality as

  10. Social technologies: Cross-disciplinary reflections on technologies in and from the social sciences

    NARCIS (Netherlands)

    Derksen, Maarten; Vikkelsø, S.; Beaulieu, Julianie

    2012-01-01

    In this introduction, we explore the relevance to critical psychology of the ideas about technology that have come from science and technology studies (STS), which we argue allow a new look at a classic theme in critical approaches in psychology. Rather than seeing psychical and social reality as

  11. A Vodcasted, Cross-Disciplinary, Behavioral Neuroscience Laboratory Exercise Investigating the Effects of Methamphetamine on Aggression

    Science.gov (United States)

    Shanks, Ryan A.; Southard, E. Megan; Tarnowski, Laura; Bruster, Matthew; Wingate, Stacia W.; Dalman, Nancy; Lloyd, Steven A.

    2011-01-01

    This article describes a laboratory experience utilizing videos to engage students in hypothesis-driven experimentation in behavioral neuroscience. It provides students with an opportunity to investigate the effects of chronic methamphetamine exposure on aggression in adult mice using a resident-intruder paradigm. Instructors and students only…

  12. Enterprise strategic alignment method: a cross-disciplinary capability-driven approach

    NARCIS (Netherlands)

    Aldea, Adina

    2017-01-01

    The environment of organisations is changing more rapidly in the recent years, which makes it increasingly more difficult to stay competitive. Organisations need to ensure that when they make transformations, they focus on maintaining or improving their strategic alignment. However, the current

  13. Feminist Scholarship: Cross-Disciplinary Connections for Cultivating a Critical Perspective in Kinesiology

    Science.gov (United States)

    Reifsteck, Erin J.

    2014-01-01

    Kinesiology has not been a particularly inviting space for feminist critical analysis. In this article, as a graduate student in the field, I argue that feminist scholarship from women and gender studies can be applied to kinesiology issues to promote a critical perspective that is often missing in kinesiology. I draw connections between feminist…

  14. It Is All about Inquiry: A Cross-Disciplinary Conversation about the Shared Foundations for Teaching

    Science.gov (United States)

    Firkins Nordstrom, Jennifer A.; Sumner, David Thomas

    2017-01-01

    This paper brings together general principles for teaching inquiry across disciplines with those generally employed in mathematics classrooms. It describes some broad principles of teaching inquiry to first-year writing students and shows how these can be employed in the context of a course on game theory in popular culture. Although undergraduate…

  15. The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model.

    Science.gov (United States)

    Reeck, Crystal; Ames, Daniel R; Ochsner, Kevin N

    2016-01-01

    Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the 'social regulatory cycle', specifies at multiple levels of description the act of regulating another person's emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. Copyright © 2015. Published by Elsevier Ltd.

  16. Crossing disciplinary boundaries in environmental research: Interdisciplinary engagement across the Slovene research community.

    Science.gov (United States)

    Rodela, Romina; Alašević, Dušan

    2017-01-01

    Contemporary approaches to environmental research are calling for a type of scientific inquiry that is able to bring together the natural and social sciences. This with the aim to advance our understanding of environmental issues and produce synthetic and actionable knowledge meant to address these. Yet, interdisciplinarity research of this type is a demanding and challenging pursuit; many have shown that in certain thematic areas and geographic regions practice falls behind discourse. We bring together ideas about interdisciplinary research collaborations (after Patricia L. Rosenfield) and interdisciplinary epistemic synthesis (after Julie T. Klein) that are used to analyse a sample of research projects funded (from 2006 to 2013) by the Slovene Research Agency. We triangulated interview data (with principal investigators) with document analysis and integrated these with other secondary data. Our results suggest for the sample of environmental projects to be interdisciplinary in a narrow sense, this prevalently within natural and life sciences with little input from the humanities and social sciences. Also, the results obtained suggest that environmental research with unambiguous problem solving objectives is preferred over research with a high degree of abstraction, as involved in theoretical and conceptual work. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. State-of-the-lagoon reports as vehicles of cross-disciplinary integration

    NARCIS (Netherlands)

    Zaucha, J.; Davoudi, S.; Slob, A.; Bouma, G.; Meerkerk, I. van; Oen, A.M.P.; Breedveld, G.D.

    2016-01-01

    An integrative approach across disciplines is needed for sustainable lagoon and estuary management as identified by integrated coastal zone management. The ARCH research project (Architecture and roadmap to manage multiple pressures on lagoons) has taken initial steps to overcome the boundaries

  18. The diffusion and use of institutional theory: A cross-disciplinary longitudinal literature survey

    OpenAIRE

    Weerakkody, V; Dwivedi, YK; Irani, Z

    2009-01-01

    There is a plethora of theories to explore the disciplines of business, management and sociology, with institutional theory being widely used to explore a range of research challenges. In the area of Information Systems (IS), the use of institutional theory remains in its infancy, with much potential for adoption. Much of the rationale underpinning the proposed research is that a systematic review and synthesis of the normative literature may support the direction of further research and the ...

  19. Cross-Disciplinary Theory in Construction of a World-Historical Archive

    Directory of Open Access Journals (Sweden)

    Patrick Manning

    2013-02-01

    Full Text Available Interdisciplinary cooperation and collaboration have proven to be desirable yet difficult goals to achieve in social science research. The nuanced differences among the domains, frameworks, assumptions, and methods of the various fields of study that comprise such research often hinder attempts to engage in interdisciplinary dialogue that is both meaningful and productive. We show that demography, economics, political science, and sociology are a few of the fields at the vanguard of the interdisciplinary frontier that emerged following the Second World War. In light of the challenges that these fields (along with the natural sciences face in initiating and sustaining interdisciplinary dialogue, we aim to accomplish several tasks. First, we seek to describe the theoretical and epistemological linkages among the cores of these four social-science disciplines. Second, we explore systems theory as a potential foundation for interdisciplinary unity. Third, we extrapolate the implications of the systems approach to encompass the study of human populations from multiple disciplinary perspectives. In this vein, we also seek to characterize key features of human populations, parse their functions in various disciplinary contexts, and prospectively identify challenges in data interpretation and analysis that will likely emerge in practice. The ultimate goals of this study are to delineate a set of methodological standards with which to guide interdisciplinary inquiry in the social and natural sciences, and consider how we might implement these standards in the construction of a world-historical data archive. 

  20. Cultural Adaptation of NNES (Non-Native English Speaking) College Faculty: A Cross-Disciplinary Study

    Science.gov (United States)

    Liu, Yingliang; Jernigan, Justin

    2012-01-01

    In order for culturally and linguistically diverse faculty members to thrive in their teaching role, it is important that their adjustment to the culture and climate of the US colleges and universities be understood and supported. To that end, this qualitatively oriented study of 28 NNES (non-native English speaking) faculty members addresses the…

  1. Structural Patterns in Empirical Research Articles: A Cross-Disciplinary Study

    Science.gov (United States)

    Lin, Ling; Evans, Stephen

    2012-01-01

    This paper presents an analysis of the major generic structures of empirical research articles (RAs), with a particular focus on disciplinary variation and the relationship between the adjacent sections in the introductory and concluding parts. The findings were derived from a close "manual" analysis of 433 recent empirical RAs from high-impact…

  2. Cross-disciplinary approaches for measuring parasitic helminth viability and phenotype

    Directory of Open Access Journals (Sweden)

    Emily Peak

    2011-06-01

    Full Text Available Parasitic worms (helminths within the Phyla Nematoda and Platyhelminthes are responsible for some of the most debilitating and chronic infectious diseases of human and animal populations across the globe. As no subunit vaccine for any parasitic helminth is close to being developed, the frontline strategy for intervention is administration of therapeutic, anthelmintic drugs. Worryingly, and unsurprising due to co-evolutionary mechanisms, many of these worms are developing resistance to the limited compound classes currently being used. This unfortunate reality has led to a renaissance in next generation anthelmintic discovery within both academic and industrial sectors. However, a major bottleneck in this process is the lack of quantitative methods for screening large numbers of small molecules for their effects on the whole organism. Development of methodologies that can objectively and rapidly distinguish helminth viability or phenotype would be an invaluable tool in the anthelmintic discovery pipeline. Towards this end, we describe how several basic techniques currently used to assess single cell eukaryote viability have been successfully applied to parasitic helminths. We additionally demonstrate how some of these methodologies have been adopted for high-throughput use and further modified for assessing worm phenotype. Continued development in this area is aimed at increasing the rate by which novel anthelmintics are identified and subsequently translated into everyday, practical applications.Vermes parasíticos (helmintos dos filos Nematoda e Platelmintos são responsáveis por algumas das doenças infecciosas crônicas e mais debilitantes das populações humana e animal em todo o globo. Já que nenhuma vacina está prestes a ser desenvolvida para nenhum parasita helmíntico, a frente estratégica de intervenção é a administração de drogas terapêuticas anti-helmínticas. De maneira preocupante, e não surpreendente devido a mecanismos coevolutivos, muitos destes vermes estão desenvolvendo resistência às limitadas classes de compostos que têm sido usados no momento. Esta infeliz realidade levou a um renascimento na descoberta de uma nova geração de anti-helmínticos tanto no setor acadêmico quanto no industrial. Contudo, um importante gargalo neste processo é a falta de métodos quantitativos para testar um grande número de pequenas moléculas em relação aos efeitos sobre o organismo inteiro. O desenvolvimento de metodologias que possam distinguir objetiva e rapidamente a viabilidade dos helmintos ou o fenótipo seria uma ferramenta valiosa para canalizar a descoberta de anti-helmínticos. Para este fim, descrevemos aqui como muitas técnicas básicas, correntemente usadas para avaliar a viabilidade de células únicas de eucariotos, têm sido aplicadas com sucesso para helmintos parasíticos. Adicionalmente demonstramos como algumas destas metodologias foram adotadas para uso em larga escala e além disso modificadas para avaliar o fenótipo de vermes. O desenvolvimento contínuo nesta área está voltado para aumentar a taxa com que novos anti-helmínticos são identificados e subsequentemente traduzidos em aplicações práticas cotidianas.

  3. Evaluating the effectiveness of a cross-disciplinary genre-focused ...

    African Journals Online (AJOL)

    In tertiary education settings it is imperative for students to move confidently between the academic discourses of a variety of disciplines. Thus, it is merited to aim writing interventions at genres that straddle disciplinary boundaries. Following a survey on preferred genres and text types at the University of Pretoria an ...

  4. Looking across the Divide: Analyzing Cross-Disciplinary Approaches for Teaching Business Communication

    Science.gov (United States)

    Laster, Nicole M.; Russ, Travis L.

    2010-01-01

    This study elucidates pedagogical differences and similarities between the ways in which instructors from business and communication disciplines teach the introductory business communication course. During the spring of 2008, the authors surveyed 444 instructors teaching this course at colleges and universities across the United States. Their…

  5. The impact of cross-disciplinary culture on student-supervisor perceptions

    National Research Council Canada - National Science Library

    Wisker, Gina; Claesson, Silwa

    2013-01-01

    Global increases in the numbers of postgraduate students, their growing cultural diversity, and an emphasis on skill development and time to completion are accompanied by an increase in the numbers...

  6. Cross-Disciplinary Variations: Japanese Novice Writers’ Socialization into the Undergraduate Thesis

    National Research Council Canada - National Science Library

    Yamada, Kiyomi

    2016-01-01

    This study investigated, by means of an ethnographic approach, what exactly occurs when Japanese novice writers are socialized into the undergraduate thesis genre and how the processes differ among disciplines...

  7. Passivity-based control and estimation in networked robotics

    CERN Document Server

    Hatanaka, Takeshi; Fujita, Masayuki; Spong, Mark W

    2015-01-01

    Highlighting the control of networked robotic systems, this book synthesizes a unified passivity-based approach to an emerging cross-disciplinary subject. Thanks to this unified approach, readers can access various state-of-the-art research fields by studying only the background foundations associated with passivity. In addition to the theoretical results and techniques,  the authors provide experimental case studies on testbeds of robotic systems  including networked haptic devices, visual robotic systems,  robotic network systems and visual sensor network systems. The text begins with an introduction to passivity and passivity-based control together with the other foundations needed in this book. The main body of the book consists of three parts. The first examines how passivity can be utilized for bilateral teleoperation and demonstrates the inherent robustness of the passivity-based controller against communication delays. The second part emphasizes passivity’s usefulness for visual feedback control ...

  8. A DSM-based framework for integrated function modelling

    DEFF Research Database (Denmark)

    Eisenbart, Boris; Gericke, Kilian; Blessing, Lucienne T. M.

    2017-01-01

    an integrated function modelling framework, which specifically aims at relating between the different function modelling perspectives prominently addressed in different disciplines. It uses interlinked matrices based on the concept of DSM and MDM in order to facilitate cross-disciplinary modelling and analysis......Function modelling is proposed in the literature from different disciplines, in interdisciplinary approaches, and used in practice with the intention of facilitating system conceptualisation. However, function models across disciplines are largely diverse addressing different function modelling...... of the functionality of a system. The article further presents the application of the framework based on a product example. Finally, an empirical study in industry is presented. Therein, feedback on the potential of the proposed framework to support interdisciplinary design practice as well as on areas of further...

  9. Prototype Biology-Based Radiation Risk Module Project

    Science.gov (United States)

    Terrier, Douglas; Clayton, Ronald G.; Patel, Zarana; Hu, Shaowen; Huff, Janice

    2015-01-01

    Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis.

  10. Intention-based and stimulus-based mechanisms in action selection.

    Science.gov (United States)

    Waszak, Florian; Wascher, Edmund; Keller, Peter; Koch, Iring; Aschersleben, Gisa; Rosenbaum, David A; Prinz, Wolfgang

    2005-04-01

    Human actions can be classified as being either more stimulus-based or more intention-based. According to the ideomotor framework of action control, intention-based actions primarily refer to anticipated action effects (in other words response-stimulus [R-S] bindings), whereas stimulus-based actions are commonly assumed to be more strongly determined by stimulus-response [S-R] bindings. We explored differences in the functional signatures of both modes of action control in a temporal bisection task. Participants either performed a choice response by pressing one out of two keys in response to a preceding stimulus (stimulus-based action), or pressed one out of two keys to produce the next stimulus (intention-based action). In line with the ideomotor framework, we found intention-based actions to be shifted in time towards their anticipated effects (the next stimulus), whereas stimulus-based actions were shifted towards their preceding stimulus. Event-related potentials (ERPs) in the EEG revealed marked differences in action preparation for the two tasks. The data as a whole provide converging evidence for functional differences in the selection of motor actions as a function of their triggering conditions, and support the notion of two different modes of action selection, one being exogenous or mainly stimulus-driven, the other being endogenous or mainly intention-driven.

  11. Arginine and Tryptophan rich antimicrobial peptides (AMPs) : modifications, application and mode of action

    OpenAIRE

    Penkova, Maya

    2010-01-01

    Da multiresistente Bakterienstämme ein häufiges Problem darstellen, besteht Bedarf an neuen Verbindungen, die keine Resistenzen hervorrufen. Eine solche Verbindungsklasse stellen die kationischen antimikrobiellen Peptide dar (cationic antimicrobial peptides, AMPs). Mithilfe von Festphasenpeptidsynthese wurden Peptide und deren Metallocenanaloga (Ferrocen- und Ruthenocenbiokonjugate) hergestellt und auf ihre biologische Aktivität untersucht. Alle hergestellten Verbindungen zeigten ...

  12. Mode-of-Action of Self-Extinguishing Polymer Blends Containing Organoclays

    Energy Technology Data Exchange (ETDEWEB)

    Pack, S.; Si, M; Koo, J; Sokolov, J; Koga, T; Kashiwagi, T; Rafailovich, M

    2009-01-01

    We have shown that the addition of nanoclays is an effective means for enhancing the flame retardant properties of polymer blends. Polymer blends are difficult to render flame retardant even with the addition of flame retardant agents due to dispersion and phase segregation during the heating process. We show that the addition of 5% functionalized Cloisite 20A clays in combination with 15% decabromodiphenyl ether and 4% antimony trioxide to a polystyrene/poly(methyl methacrylate) blend can render the compound flame resistant within the UL-94-V0 standard. Using a variety of micro-characterization methods, we show that the clays are concentrated at the interfaces between the polymers in this blend and completely suppress phase segregation. The flame retardant (FR) is absorbed onto the clay surfaces, and the exfoliation of the clays also distributes the FR agent uniformly within the matrix. TGA of the nanocomposite indicates that prior to the addition of clay, the dissociation times of the individual components varied by more than 20 C, which complicated the gas-phase kinetics. Addition of the clays causes all the components to have a single dissociation temperature, which enhanced the efficacy of the FR formula in the gas phase. Cone calorimetry also indicated that the clays decreased the heat release rate (HRR) and the mass loss rate (MLR), due to the formation of a robust char. In contrast, minimal charring occurred in blends containing just the FR. SEM examination of the chars showed that the clay platelets were curved and in some cases tightly folded into nanotube-like structures. These features were only apparent in blends, indicating that they might be associated with thermal gradients across the polymer phase interface. SEM and SAXS examinations of the nanocomposites after partial exposure to the flame indicated that the clays aggregated into ribbon-like structures, approximately microns in length, after the surfactant thermally decomposed. Thermal modeling indicated that these ribbons might partially explain the synergy due to better distribution of the heat and improve the mechanical properties of the melt at high temperatures, in a manner similar to the one reported for carbon nanotubes.

  13. Biogenic silver nanoparticles synthesized with rhamnogalacturonan gum: Antibacterial activity, cytotoxicity and its mode of action

    Directory of Open Access Journals (Sweden)

    Aruna Jyothi Kora

    2018-03-01

    Full Text Available Silver nanoparticles synthesized from gum kondagogu (5 nm were used to evaluate the antibacterial activity against Gram-positive and Gram-negative bacteria. To decipher the mode of antibacterial action of nanoparticles, a comprehensive study was carried out employing a variety of susceptibility assays: micro-broth dilution, antibiofilm activity, growth kinetics, cytoplasmic content leakage, membrane permeabilization, etc. The production of reactive oxygen species (ROS and cell surface damage during bacterial nanoparticle interaction were also demonstrated using dichlorodihydrofluorescein diacetate, N-acetylcysteine; and scanning electron microscopy and energy dispersive X-ray spectra. Further, the biocompatibility with HeLa cell line was also evaluated. Compared to earlier reports, the minimum inhibitory concentration values were lower by 3.2- and 16-folds for Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli strains, respectively. The minimum bactericidal concentration values were lower by 4 and 50-folds. Thus, the biogenic silver nanoparticles were found to be more potent bactericidal agents in terms of concentration. The nanoparticles exhibited significant antibiofilm activity against test strains at 2 μg mL−1, which can have implications in the treatment of drug resistant bacterial infections caused by biofilms. Growth curve in nanoparticle supplemented indicated a faster inhibition in Gram-negative bacteria as compared to Gram-positive. Treatment with nanoparticles caused cytoplasmic content leakage and membrane permeabilization in a dose dependent manner, an evidence for membrane damage. The observations noted in our study substantiated the association of ROS and membrane damage in the antibacterial action of silver nanoparticles. The promising antibacterial activity enables these nanoparticles as potential bactericidal material for various environmental and biomedical applications.

  14. Mode of action and herbicide potential of the therpenoids farnesene and citral on "Arabidopsis thaliana" metabolism

    OpenAIRE

    Graña Martinez, Elisa

    2015-01-01

    En los últimos 50 años, el abuso de los herbicidas de síntesis química ha provocado la aparición de malas hierbas resistentes. Esto se debe a que, por lo general, los herbicidas clásicos actúan sobre una única diana molecular, la cual se suele encontrar bajo el control de un único gen o de un conjunto de pocos genes, lo que favorece la aparición de resistencias. Pero este no es el único problema derivado de su uso, ya que se ha comprobado que su degradación en el medio es complicada y que tie...

  15. Fish Reproduction Is Disrupted upon Lifelong Exposure to Environmental PAHs Fractions Revealing Different Modes of Action

    Directory of Open Access Journals (Sweden)

    Caroline Vignet

    2016-10-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs constitute a large family of organic pollutants emitted in the environment as complex mixtures, the compositions of which depend on origin. Among a wide range of physiological defects, PAHs are suspected to be involved in disruption of reproduction. In an aquatic environment, the trophic route is an important source of chronic exposure to PAHs. Here, we performed trophic exposure of zebrafish to three fractions of different origin, one pyrolytic and two petrogenic. Produced diets contained PAHs at environmental concentrations. Reproductive traits were analyzed at individual, tissue and molecular levels. Reproductive success and cumulative eggs number were disrupted after exposure to all three fractions, albeit to various extents depending on the fraction and concentrations. Histological analyses revealed ovary maturation defects after exposure to all three fractions as well as degeneration after exposure to a pyrolytic fraction. In testis, hypoplasia was observed after exposure to petrogenic fractions. Genes expression analysis in gonads has allowed us to establish common pathways such as endocrine disruption or differentiation/maturation defects. Taken altogether, these results indicate that PAHs can indeed disrupt fish reproduction and that different fractions trigger different pathways resulting in different effects.

  16. SLAMF6 and 2B4: Roles and modes of action in normal immunity ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    A functioning immune system is critical for successful treatment of cancer. Recent studies have shown an improvement of the immune response against cancer triggered by new drugs that block the function of certain types of receptors at the surface of immune cells. This project seeks to understand the role of two new ...

  17. Alcohol dehydrogenase of acetic acid bacteria: structure, mode of action, and applications in biotechnology.

    Science.gov (United States)

    Yakushi, Toshiharu; Matsushita, Kazunobu

    2010-05-01

    Pyrroquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) of acetic acid bacteria is a membrane-bound enzyme involved in the acetic acid fermentation by oxidizing ethanol to acetaldehyde coupling with reduction of membranous ubiquinone (Q), which is, in turn, re-oxidized by ubiquinol oxidase, reducing oxygen to water. PQQ-ADHs seem to have co-evolved with the organisms fitting to their own habitats. The enzyme consists of three subunits and has a pyrroloquinoline quinone, 4 heme c moieties, and a tightly bound Q as the electron transfer mediators. Biochemical, genetic, and electrochemical studies have revealed the unique properties of PQQ-ADH since it was purified in 1978. The enzyme is unique to have ubiquinol oxidation activity in addition to Q reduction. This mini-review focuses on the molecular properties of PQQ-ADH, such as the roles of the subunits and the cofactors, particularly in intramolecular electron transport of the enzyme from ethanol to Q. Also, we summarize biotechnological applications of PQQ-ADH as to enantiospecific oxidations for production of the valuable chemicals and bioelectrocatalysis for sensors and fuel cells using indirect and direct electron transfer technologies and discuss unsolved issues and future prospects related to this elaborate enzyme.

  18. [Femtosecond laser for refractive corneal surgery: foundations, mode of action and clinical applications].

    Science.gov (United States)

    Mrochen, M; Donges, A; Korn, G

    2006-12-01

    Modern corneal laser surgery for the correction of optical errors of the eye requires a precise, reliable and reproducible creation of corneal lenticels (flaps). The use of ultra-short laser pulses with pulse durations of a few 100 femtoseconds (10(-13) s) allows for non-thermal cuts of ocular tissue. Mean flap thicknesses as small as 100 microm with a reproducibility of 10 microm (standard deviation) can be created by using mechano-optical adaptations through the eye. Thus, the femtosecond laser can be considered a good alternative approach with a safety in clinical use that is comparable with that of mechanical microkeratomes.

  19. Mode of action and membrane specificity of the antimicrobial peptide snakin-2

    Directory of Open Access Journals (Sweden)

    Vera Herbel

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are a diverse group of short, cationic peptides which are naturally occurring molecules in the first-line defense of most living organisms. They represent promising candidates for the treatment of pathogenic microorganisms. Snakin-2 (SN2 from tomato (Solanum lycopersicum is stabilized through six intramolecular disulphide bridges; it shows broad-spectrum antimicrobial activity against bacteria and fungi, and it agglomerates single cells prior to killing. In this study, we further characterized SN2 by providing time-kill curves and corresponding growth inhibition analysis of model organisms, such as E. coli or B. subtilis. SN2 was produced recombinantly in E. coli with thioredoxin as fusion protein, which was removed after affinity purification by proteolytic digestion. Furthermore, the target specificity of SN2 was investigated by means of hemolysis and hemagglutination assays; its effect on plant cell membranes of isolated protoplasts was investigated by microscopy. SN2 shows a non-specific pore-forming effect in all tested membranes. We suggest that SN2 could be useful as a preservative agent to protect food, pharmaceuticals, or cosmetics from decomposition by microbes.

  20. Elucidating antimalarial drug targets/mode-of-action by application of system biology technologies

    CSIR Research Space (South Africa)

    Becker, J

    2008-11-01

    Full Text Available Malaria is one of the world's most important tropical diseases, killing more than a million of an estimated 300-500 million infected people per annum. The species responsible for the most fatalities amongst the genus is Plasmodium falsiparum...

  1. Flavonols and fertilization in Petunia hybrida: localization and mode of action during pollen tube growth

    NARCIS (Netherlands)

    Ylstra, B.; Busscher, J.; Franken, J.; Hollman, P.C.H.; Mol, J.N.M.; Tunen, van A.J.

    1995-01-01

    Flavonols form an important class of flavonoids which serve an essential function during plant reproduction. Flavonoid biosynthesis is initiated by the enzyme chalcone synthase (CHS). A high abundance of flavonols and chs mRNA was demonstrated in male and female reproductive organs of Petunia

  2. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis

    Science.gov (United States)

    Wex, Eva; Pautsch, Alexander; Schnapp, Gisela; Hostettler, Katrin E.; Stowasser, Susanne; Kolb, Martin

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials. PMID:25745043

  3. PROBIOTICS, PREBIOTICS AND SNYBIOTICS IN POULTRY MODE OF ACTION, LIMITATION, AND ACHIEVEMENTS

    Directory of Open Access Journals (Sweden)

    Agata DANKOWIAKOWSKA

    2013-03-01

    Full Text Available The withdrawal of antibiotic growth promoters from poultry industry have forced farmers to seek alternatives for the posing a risk factors of cross-resistance acquisition by harmful bacteria. A particular nuisance became salmonellosis and campylobacteriosis forcing to the elimination of whole poultry flocks as well as causing dangerous zoonotic diseases in humans. An excellent replacement for antibiotics have become the pro-, pre-and synbiotic substances which have a beneficial effect on the host organism through the development intensification of healthy intestinal microbial strains and the elimination of pathogenic strains. Such preparations may be administered both in the water spray as well as in feed. Excellent and promising method appears to be their injection directly into the egg air chamber in the 12th day of incubation. However, further studies are required to determine the appropriate doses as well as combinations of bioactive substances and to determine the optimal way for their delivery.

  4. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents

    National Research Council Canada - National Science Library

    Almeida, Joana R; Freitas, Micaela; Cruz, Susana; Leão, Pedro N; Vasconcelos, Vitor; Cunha, Isabel

    2015-01-01

    .... Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity...

  5. Proceedings of the 2006 Toxicology and Risk Assessment Conference: Applying Mode of Action in Risk Assessment

    Science.gov (United States)

    2006-07-01

    tubular proteinuria patterns which were most marked for InAs–treated animals at the 30 day time point. Confirmatory in vitro studies using primary...water and 150 ng of internal standard (d26-dodecane in 1 µl of chloroform). After heating the sample for 45 min at 65oC the SPME fiber (100 µm PDMS

  6. The Mode of Action of Silver and Silver Halides Nanoparticles against Saccharomyces cerevisiae Cells

    Directory of Open Access Journals (Sweden)

    A. A. Kudrinskiy

    2014-01-01

    Full Text Available Silver and silver halides nanoparticles (NPs (Ag, AgCl, AgBr, and AgI capped with two different stabilizers (sodium citrate and nonionic surfactant Tween 80 were obtained via sodium borohydride reduction of silver nitrate in an aqueous solution. The effect of the biocidal action of as-prepared synthesized materials against yeast cells Saccharomyces cerevisiae was compared to the effect produced by silver nitrate and studied through the measurement of cell loss and kinetics of K+ efflux from the cells depending on concentration of silver. The results clearly indicate that the silver ions either remained in the dispersion of silver NPs and silver halides NPs after their synthesis or were generated afterwards by dissolving silver and silver halides particles playing a major part in the cytotoxic activity of NPs against yeast cells. It was also supposed that this activity most likely does not relate to the damage of cell membrane.

  7. The antifungal activity of Natamycin : a novel mode of action of the polyene antibiotics

    NARCIS (Netherlands)

    te Welscher, Y.M.|info:eu-repo/dai/nl/304837733

    2010-01-01

    Fungal infections have recently become a growing threat to human health, especially in persons whose immune systems are compromised (for example transplant recipients or patients with HIV or cancer). Only a few effective antifungal agents are currently in use and a major problem is the increase of

  8. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review

    DEFF Research Database (Denmark)

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad

    2016-01-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied...

  9. Metformin--mode of action and clinical implications for diabetes and cancer.

    Science.gov (United States)

    Pernicova, Ida; Korbonits, Márta

    2014-03-01

    Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer.

  10. Changing the field of carcinogenicity testing of human pharmaceuticals by emphasizing mode of action

    NARCIS (Netherlands)

    Laan, J.W. van der; Duijndam, B.; Hoorn, T. van den; Woutersen, R.; Water, B. van de

    2017-01-01

    Lifetime testing for carcinogenicity of pharmaceuticals in rodents has been a controversial issue since the start of the International Conference on Harmonisation in 1990. Since 2010 the debate reached a new level following the proposal that a negative outcome of carcinogenicity studies can be

  11. [Antifreeze glycoproteins in fishes: structure, mode of action and possible applications].

    Science.gov (United States)

    Wöhrmann, A

    1996-02-01

    Two types of antifreezes have been isolated from polar and northern temperate fishes so far. They are either glycopeptides or peptides. Whereas these proteins have only a very small effect on the melting temperature of ice, the temperature of these fish can fall to nearly 1 degree below the melting point before ice crystals grow. This phenomenon is called thermal hysteresis, in contrast to the normal colligative effect of solutes. All Antarctic notothenioids (perches) investigated so far have the typical antifreeze glycoproteins (AFGP) with the tripeptide Ala-Ala-Thr and the disaccharide Gal-GalNAc. In the Antarctic silverfish Pleuragramma antarcticum there could be found a novel GlcNAc containing antifreeze glycoprotein, the PAGP. The antifreezes not only lower the freezing temperature, but they also retard recrystallization on frozen storage. Antifreeze proteins thus could be useful for biotechnology and cryomedicine in the future. Since some are now synthesized chemically or by genetic engineering, they no longer have to be isolated from fish blood.

  12. Mode of action of FK-506 on protective immunity to Hymenolepis nana in mice.

    Science.gov (United States)

    Asano, K; Taki, M; Matsuo, S; Yamada, K

    1996-01-01

    FK-506 (Tacrolimus) has been shown to block T cell proliferation in vitro by inhibiting the generation of several lymphokines, especially interleukin (IL)-2, but little direct evidence is available to support the view that the immunosuppressive effects of FK-506 in vivo are mediated by a similar inhibition of lymphokine cascade. To investigate the mechanisms of FK-506-induced immunosuppression, the effects of FK-506 on cell-mediated immunity to Hymenolepis nana were examined in mice. FK-506 administration into BALB/c mice daily at a dose of 10.0 mg/kg (but not 5.0 mg/kg) for 5 days caused suppression of protective immunity against H. nana challenge infection. During the infection of mice with H. nana, IL-2 and interferon (IFN)-gama were produced by mesenteric lymph node (MLN) cells with a time course corresponding to that of MLN T cell proliferation. These responses were completely suppressed by repeated administration of FK-506 for 5 days at a dose of 10.0 mg/kg/day (but not 5.0 mg/kg/day). In contrast to the effects of FK-506 on IL-2 and IFN-gamma productions in MLN, IL-1 and tumor necrosis factor-alpha in the intestinal wall, which were enhanced by H. nana infection, were not completely decreased as a result of 10.0 mg/kg FK-506 treatment. The reverse transcriptase-PCR revealed complete inhibition of IL-2 and IFN-gamma mRNA expression on mesenteric L3T4+ cells that were induced by H. nana infection, when mice were given 10.0 mg/kg/day FK-506 for 5 days. These results strongly suggest that FK-506 affects cell-mediated immunity in vivo with mechanisms similar to those observed in vitro.

  13. Solubilization of lipids and membrane proteins into nanodiscs : Mode of action and applications of SMA copolymers

    OpenAIRE

    Scheidelaar, S.

    2016-01-01

    Cell membranes separate the inside and outside of cells. Membrane proteins in the cell membrane control the traffic of molecules across the membrane and are therefore targets for a lot of drugs: about 50 % of all approved drugs target a membrane protein! Unfortunately, scientists only know little about membrane proteins as compared to, for example, water soluble proteins. That is because membrane proteins are hard to study since they reside in the hydrophobic patch of the membrane. To study m...

  14. Insights into the Mode of Action of the Sactibiotic Thuricin CD

    Directory of Open Access Journals (Sweden)

    Colin Hill

    2017-04-01

    Full Text Available Thuricin CD is a two-component bacteriocin, consisting of the peptides Trnα and Trnβ, and belongs to the newly designated sactibiotic subclass of bacteriocins. While it is clear from studies conducted thus far that it is a narrow-spectrum bacteriocin, requiring the synergistic activity of the two peptides, the precise mechanism of action of thuricin CD has not been elucidated. This study used a combination of flow cytometry and traditional culture-dependent assays to ascertain the effects of the thuricin CD peptides on the morphology, physiology and viability of sensitive Bacillus firmus DPC6349 cells. We show that both Trnα and Trnβ are membrane-acting and cause a collapse of the membrane potential, which could not be reversed even under membrane-repolarizing conditions. Furthermore, the depolarizing action of thuricin CD is accompanied by reductions in cell size and granularity, producing a pattern of physiological alterations in DPC6349 cells similar to those triggered by the pore-forming single-component bacteriocin Nisin A, and two-component lacticin 3147. Taken together, these results lead us to postulate that the lytic activity of thuricin CD involves the insertion of thuricin CD peptides into the membrane of target cells leading to permeabilization due to pore formation and consequent flux of ions across the membrane, resulting in membrane depolarization and eventual cell death.

  15. Macromolecule biosynthesis assay and fluorescence spectroscopy methods to explore antimicrobial peptide mode(s) of action

    DEFF Research Database (Denmark)

    Jana, Bimal; Baker, Kristin Renee; Guardabassi, Luca

    2017-01-01

    Antimicrobial peptides (AMPs) are viable alternatives to the currently available antimicrobials, and numerous studies have investigated their possible use as therapeutic agents for specific clinical applications. AMPs are a diverse class of antimicrobials that often act upon the bacterial cell me...

  16. Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

    DEFF Research Database (Denmark)

    van der Stelt, M.; Veldink, G.A.; Vliegenthart, J.F.G.

    2003-01-01

    Endocannabinoids are thought to function as retrograde messengers, which modulate neurotransmitter release by activating presynaptic cannabinoid receptors. Anandamide and 2-arachidonoylglycerol (2-AG) are the two best studied endogenous lipids which can act as endocannabinoids. Together...... with the proteins responsible for their biosynthesis, inactivation and the cannabinoid receptors, these lipids constitute the endocannabinoid system. This system is proposed to be involved in various neurodegenerative diseases such as Parkinson's and Huntington's diseases as well as Multiple Sclerosis. It has been...

  17. Investigations of organic fungicides. VIII. The biochemical mode of action of bisdithiocarbamates and diisothiocyanates

    NARCIS (Netherlands)

    Kaars Sijpesteijn, A.; Kerk, G.J.M. van der

    1954-01-01

    The inhibitory action of tetramethylene diisothiocyanate (TMDI) and of disodium ethylene bisdithiocarbamate (nabam) on the spore germination of Penicillium italicum and of Aspergillus niger is strongly antagonized by the thiol compounds, thioglycollic acid and cysteine. This antagonism is supposed

  18. Relative value and mode of action of some fungicides used as seed disinfectants and protectants

    NARCIS (Netherlands)

    Samra, A.S.

    1956-01-01

    The first part of this paper deals with investigations at the Phytopathological Laboratory, Wageningen, into the control of Alternaria spp. (mainly A . raphani) on radish seed by chemicals. Organic mercury compounds proved better than thiram products and were more

  19. Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

    Directory of Open Access Journals (Sweden)

    Thazin Nwe Aung

    2017-03-01

    Full Text Available Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.

  20. β-Lactams: chemical structure, mode of action and mechanisms of resistance

    OpenAIRE

    Fernandes, Rúben; Amador, Paula; Prudêncio, Cristina

    2013-01-01

    This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases an...

  1. Mode of action of interleukin-1 in suppression of pituitary LH release in castrated male rats.

    Science.gov (United States)

    Bonavera, J J; Kalra, S P; Kalra, P S

    1993-05-28

    These studies were undertaken to elucidate the mechanisms whereby the cytokine, Interleukin (IL-1) suppresses pituitary LH release in orchidectomized rats. Since LH secretion is pulsatile in castrated rats, the effects of IL-1 on the components of the LH pulsatility were assessed. Intracerebroventricular (i.c.v.) administration of IL-1 alpha or IL-1 beta suppressed LH release, but IL-1 beta was relatively more effective than IL-1 alpha in terms of the onset (IL-1 beta = 30 min; IL-1 alpha = 105 min) as well as the magnitude and duration of LH suppression. Further, the marked suppression of LH secretion in IL-1 beta-treated rats was found to be due to significant reductions both in the frequency and amplitude of LH episodes. We next evaluated whether the IL-1 beta-induced suppression of LH release was mediated by either of the two inhibitory hypothalamic peptidergic systems, corticotrophin releasing hormone (CRH) and endogenous opioid peptides (EOP). Passive immunoneutralization of CRH by i.c.v. administration of a specific CRH-antibody, either once at 15 min or twice at 75 and 15 min before IL-1 beta injection, failed to block the suppressive effects of IL-1 beta on LH release. Similarly, pharmacological blockade of CRH by i.c.v. injection of the CRH receptor antagonist, alpha-helical CRH9-41 15 min before IL-1 beta was ineffective. However, i.v. infusion of the opiate receptor antagonist, naloxone, which on its own had no effect on LH secretion, counteracted the inhibitory effects of IL-1 beta. To further identify the opiate receptor subtype involved, we utilized specific opiate receptor subtype antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action

    DEFF Research Database (Denmark)

    Hansen, J E; Witzke, N M; Nielsen, C

    1990-01-01

    /ml; N-(N'-(3-dimethylaminopropyl)N"-ethyl guanyl) amphotericin B (DAPEG) did so at 5-11 micrograms/ml. While the virus-inhibitory effect of AME was due to an interaction with target lymphocytes, the effect of MCG was due to a direct anti-viral action. AME increased the potential of infected cells...

  3. Physiological modes of action of toxic chemicals in the nematode acrobeloides nanus

    NARCIS (Netherlands)

    Alda Alvarez, O.; Jager, T.; Redondo, E.M.; Kammenga, J.E.

    2006-01-01

    To gain a better understanding of the mechanisms through which a chemical exerts toxicity, a deeper insight is needed regarding the physiological processes that take place during a toxic stress. This issue can have important benefits for risk assessment, because it can contribute to a better

  4. Influence of nitrogen rate on the efficacy of herbicides with different modes of action

    DEFF Research Database (Denmark)

    Sønderskov, Mette; Swanton, C. J.; Kudsk, Per Nielsen

    2012-01-01

    Outdoor pot experiments and field experiments were conducted to examine the influence of nitrogen rate on herbicide efficacy. Growth of unsprayed Tripleurospermum inodorum increased with increasing nitrogen rate in pot experiments; increasing nitrogen also increased the susceptibility to tribenur...

  5. Cytotoxicity and mode of action of maleic hydrazide in root tips of Allium cepa L.

    Science.gov (United States)

    Marcano, L; Carruyo, I; Del Campo, A; Montiel, X

    2004-02-01

    Maleic hydrazide (MH) is an herbicide and is a regulator of the growth of buds in vegetables during storage. It is used in agriculture-in despite its known effect as a mutagenic and clastogenic agent. In this research the effect of MH on the root tips of Allium cepa L. was determined; correlations between the effects of different concentrations and exposure times on the mitotic index (MI) and induction of chromosomal aberrations (ChA) were also examined. Experiments were carried out in triplicate, using aqueous solutions of MH to concentrations of 10(-6), 10(-5), 10(-4) and 10(-3)M, at intervals of 0, 4, 8, 12, 24, and 48 h, with a control for each combination (with the MH substituted by distilled water). The results revealed an inhibition of the MI linked to the concentration and time of treatment (F=845.51, P<0.01 and F=427.58, P<0.01, respectively). For all the concentrations used and exposure periods longer than 12 h, different types of ChA were present, with significantly increased frequencies with increases in the concentration and time of exposure (P<0.01). To determine the mechanism through which the herbicide exerts its toxicity, ultrastructural electron microscopy was conducted. The results reveal nucleolar alterations, suggesting an inhibitory effect of biosynthetic activity.

  6. Antimicrobial compounds targeting Gram-negative bacteria in food: Their mode of action and combinational effects

    DEFF Research Database (Denmark)

    Hyldgaard, Morten

    2015-01-01

    Gram-negative bacteria are a major cause of food spoilage and foodborne illnesses. However, finding effective solutions against Gram-negative bacteria are complicated because of increasing consumer demands for more natural, minimally processed, and fresh high quality food products without...... they interact with bacterial cells to exert their mechanism of inhibition or killing. Furthermore, natural antimicrobials are often not potent enough as single compounds, and may cause unwanted sensory side-effects, which limit the quantities that can be applied to food. These problems might be circumvented...... by combining antimicrobials to decrease the concentrations needed without compromising their antimicrobial activity. The work described in this dissertation presents two projects concerning the mechanism of action of selected natural antimicrobial compounds primarily against Gram-negative bacteria, and two...

  7. Structural and functional insights into the mode of action of a universally conserved Obg GTPase.

    Directory of Open Access Journals (Sweden)

    Boya Feng

    2014-05-01

    Full Text Available Obg proteins are a family of P-loop GTPases, conserved from bacteria to human. The Obg protein in Escherichia coli (ObgE has been implicated in many diverse cellular functions, with proposed molecular roles in two global processes, ribosome assembly and stringent response. Here, using pre-steady state fast kinetics we demonstrate that ObgE is an anti-association factor, which prevents ribosomal subunit association and downstream steps in translation by binding to the 50S subunit. ObgE is a ribosome dependent GTPase; however, upon binding to guanosine tetraphosphate (ppGpp, the global regulator of stringent response, ObgE exhibits an enhanced interaction with the 50S subunit, resulting in increased equilibrium dissociation of the 70S ribosome into subunits. Furthermore, our cryo-electron microscopy (cryo-EM structure of the 50S·ObgE·GMPPNP complex indicates that the evolutionarily conserved N-terminal domain (NTD of ObgE is a tRNA structural mimic, with specific interactions with peptidyl-transferase center, displaying a marked resemblance to Class I release factors. These structural data might define ObgE as a specialized translation factor related to stress responses, and provide a framework towards future elucidation of functional interplay between ObgE and ribosome-associated (pppGpp regulators. Together with published data, our results suggest that ObgE might act as a checkpoint in final stages of the 50S subunit assembly under normal growth conditions. And more importantly, ObgE, as a (pppGpp effector, might also have a regulatory role in the production of the 50S subunit and its participation in translation under certain stressed conditions. Thus, our findings might have uncovered an under-recognized mechanism of translation control by environmental cues.

  8. Multiple novel modes of action involved in the in vitro neurotoxic effects of tetrabromobisphenol-A

    NARCIS (Netherlands)

    Hendriks, H.S.|info:eu-repo/dai/nl/32323738X; van Kleef, R.G.D.M.; van den Berg, M.|info:eu-repo/dai/nl/08660466X; Westerink, R.H.S.|info:eu-repo/dai/nl/239425952

    2012-01-01

    Neurotoxicological data on the widely used brominated flame retardant tetrabromobisphenol-A (TBBPA) is limited. Since recent studies indicated that inhibitory GABA(A) and excitatory α(4)β(2) nicotinic acetylcholine (nACh) receptors are sensitive targets for persistent organic pollutants, we

  9. Antiviral activity and mode of action of propolis extracts and selected compounds.

    Science.gov (United States)

    Schnitzler, Paul; Neuner, Annett; Nolkemper, Silke; Zundel, Christine; Nowack, Hans; Sensch, Karl Heinz; Reichling, Jürgen

    2010-01-01

    Aqueous and ethanol extracts of propolis were analysed phytochemically and examined for their antiviral activity in vitro. Different polyphenols, flavonoids and phenylcarboxylic acids were identified as major constituents. The antiviral effect of propolis extracts and selected constituents, e.g. caffeic acid (1), p-coumaric acid (2), benzoic acid (3), galangin (4), pinocembrin (5) and chrysin (6) against herpes simplex virus type 1 (HSV-1) was analysed in cell culture. The 50% inhibitory concentration (IC(50)) of aqueous and ethanol propolis extracts for HSV-1 plaque formation was determined at 0.0004% and 0.000035%, respectively. Both propolis extracts exhibited high levels of antiviral activity against HSV-1 in viral suspension tests, plaque formation was significantly reduced by >98%. In order to determine the mode of antiviral action of propolis, the extracts were added at different times during the viral infection cycle. Both propolis extracts exhibited high anti-HSV-1 activity when the viruses were pretreated with these drugs prior to infection. Among the analysed compounds, only galangin and chrysin displayed some antiviral activity. However, the extracts containing many different components exhibited significantly higher antiherpetic effects as well as higher selectivity indices than single isolated constituents. Propolis extracts might be suitable for topical application against herpes infection.

  10. Bactericidal efficiency and mode of action: a comparative study of photochemistry and photocatalysis.

    Science.gov (United States)

    Pigeot-Rémy, S; Simonet, F; Atlan, D; Lazzaroni, J C; Guillard, C

    2012-06-15

    In order to compare the disinfection potential of photocatalysis and photochemistry, the effects of these two processes on bacteria in water were investigated under exposure to UV-A and UV-C. The well-known bacterial model Escherichia coli (E. coli) was used as the experimental organism. Radiation exposure was produced with an HPK 125 W lamp and the standard TiO(2) Degussa P-25 was used as the photocatalyst. Firstly, the impact of photocatalysis and photochemistry on the cultivability of bacterial cells was investigated. UV-A radiation resulted in low deleterious effects on bacterial cultivability but generated colonies of size smaller than average. UV-C photocatalysis demonstrated a greater efficiency than UV-A photocatalysis in altering bacterial cultivability. From a cultivability point of view only, UV-C radiation appeared to be the most deleterious treatment. A rapid epifluorescence staining method using the LIVE/DEAD Bacterial Viability Kit was then used to assess the modifications in bacterial membrane permeability. UV-A radiation did not induce any alterations in bacterial permeability for 420 min of exposure whereas only a few minutes of exposure to UV-C radiation, with the same total radiance intensity, induced total loss of permeability. Moreover, after 20 and 60 min of exposure to UV-C and UV-A photocatalysis respectively, all bacteria lost their membrane integrity, suggesting that the bacterial envelope is the primary target of reactive oxygen species (ROS) generated at the surface of TiO(2) photocatalyst. These results were further confirmed by the formation of malondialdehyde (MDA) during the photocatalytic inactivation of bacterial cells and suggest that destruction of the cell envelope is a key step in the bactericidal action of photocatalysis. The oxidation of bacterial membrane lipids was also correlated with the monitoring of carboxylic acids, which can be considered as representatives of lipid peroxidation by-products. Finally, damages to bacterial morphology induced by UV-C photocatalysis and photochemistry were investigated through Scanning electron microscopy (SEM). Bacterial cells were observed on microscopy pictures at exposure durations corresponding to a loss of cultivability. After 90 min of exposure to UV-C radiation, bacterial cells showed little alteration of their outer membrane whereas they suffered deep deleterious damages under UV-C photocatalysis exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Mode of action of xylogalacturonan hydrolase towards xylogalacturonan and xylogalacturonan oligosaccharides

    NARCIS (Netherlands)

    Zandleven, J.S.; Beldman, G.; Bosveld, M.; Benen, J.A.E.; Voragen, A.G.J.

    2005-01-01

    XGH (xylogalacturonan hydrolase; GH 28) is an enzyme that is capable of degrading XGA (xylogalacturonan), which is a polymer of ¿-D-galacturonic acid, highly substituted with ß-D-xylose. XGA is present in cell walls of various plants and exudates, such as gum tragacanth. XGA oligosaccharides were

  12. The mode of action of recombinant Mycobacterium tuberculosis shikimate kinase: kinetics and thermodynamics analyses.

    Directory of Open Access Journals (Sweden)

    Leonardo Astolfi Rosado

    Full Text Available Tuberculosis remains as one of the main cause of mortality worldwide due to a single infectious agent, Mycobacterium tuberculosis. The aroK-encoded M. tuberculosis Shikimate Kinase (MtSK, shown to be essential for survival of bacilli, catalyzes the phosphoryl transfer from ATP to the carbon-3 hydroxyl group of shikimate (SKH, yielding shikimate-3-phosphate and ADP. Here we present purification to homogeneity, and oligomeric state determination of recombinant MtSK. Biochemical and biophysical data suggest that the chemical reaction catalyzed by monomeric MtSK follows a rapid-equilibrium random order of substrate binding, and ordered product release. Isothermal titration calorimetry (ITC for binding of ligands to MtSK provided thermodynamic signatures of non-covalent interactions to each process. A comparison of steady-state kinetics parameters and equilibrium dissociation constant value determined by ITC showed that ATP binding does not increase the affinity of MtSK for SKH. We suggest that MtSK would more appropriately be described as an aroL-encoded type II shikimate kinase. Our manuscript also gives thermodynamic description of SKH binding to MtSK and data for the number of protons exchanged during this bimolecular interaction. The negative value for the change in constant pressure heat capacity (ΔCp and molecular homology model building suggest a pronounced contribution of desolvation of non-polar groups upon binary complex formation. Thermodynamic parameters were deconvoluted into hydrophobic and vibrational contributions upon MtSK:SKH binary complex formation. Data for the number of protons exchanged during this bimolecular interaction are interpreted in light of a structural model to try to propose the likely amino acid side chains that are the proton donors to bulk solvent following MtSK:SKH complex formation.

  13. Bioefficacy and mode-of-action of some limonoids of salannin group ...

    Indian Academy of Sciences (India)

    Unknown

    In nutritional assays, all three compounds reduced growth and consumption when fed to larvae without any effect on efficiency of conversion of ingested food (ECI), suggesting antifeedant activity alone. No toxicity was observed nor was there any significant affect on nutritional indices following topical appli- cation, further ...

  14. Acute sensitivity of freshwater mollusks to select chemicals with various toxic modes of action

    Science.gov (United States)

    Nearly 70% of the 300 unionid mussel species in North America are endangered, threatened, of special concern, or already extinct. Environmental contamination has been identified as a causal or contributing factor to these declines of mussel populations. Previous studies indicate ...

  15. PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

    Science.gov (United States)

    Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

  16. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

    Directory of Open Access Journals (Sweden)

    Srivastava Harish C

    2011-01-01

    Full Text Available Abstract Background Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. Results A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively and An. stephensi strains (0.43 and 2.13% respectively and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05. Residual activity of chlorfenapyr a.i. of 400 mg/m2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies. Potentiation studies demonstrated the antagonistic effect of PBO. Conclusion Laboratory studies with susceptible and resistant strains of An. culicifacies and An. stephensi, coupled with limited field studies with multiple insecticide-resistant An. culicifacies have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.

  17. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

    OpenAIRE

    Srivastava Harish C; Bhatt Rajendra M; Sharma Poonam; Barik Tapan K; Raghavendra Kamaraju; Sreehari Uragayala; Dash Aditya P

    2011-01-01

    Abstract Background Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods Efficacy of chlorfenapyr against An. culicifacies and An. ...

  18. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors.

    Science.gov (United States)

    Raghavendra, Kamaraju; Barik, Tapan K; Sharma, Poonam; Bhatt, Rajendra M; Srivastava, Harish C; Sreehari, Uragayala; Dash, Aditya P

    2011-01-25

    Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively) and An. stephensi strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies. Potentiation studies demonstrated the antagonistic effect of PBO. Laboratory studies with susceptible and resistant strains of An. culicifacies and An. stephensi, coupled with limited field studies with multiple insecticide-resistant An. culicifacies have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.

  19. Solubilization of lipids and membrane proteins into nanodiscs : Mode of action and applications of SMA copolymers

    NARCIS (Netherlands)

    Scheidelaar, S.

    2016-01-01

    Cell membranes separate the inside and outside of cells. Membrane proteins in the cell membrane control the traffic of molecules across the membrane and are therefore targets for a lot of drugs: about 50 % of all approved drugs target a membrane protein! Unfortunately, scientists only know little

  20. Study of the mode of action of a polygalacturonase from the phytopathogen Burkholderia cepacia

    DEFF Research Database (Denmark)

    Massa, C.; Clausen, Mads Hartvig; Stojan, J.

    2007-01-01

    We have recently isolated and heterologously expressed BcPeh28A, an endopolygalacturonase from the phytopathogenic Gram-negative bacterium Burkholderia cepacia. Endopolygalacturonases belong to glycoside hydrolase family 28 and are responsible for the hydrolysis of the non-esterified regions of p...

  1. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    Directory of Open Access Journals (Sweden)

    Rae-Dong Jeong

    2016-04-01

    Full Text Available Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc. Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika.

  2. Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

    Science.gov (United States)

    Chopra, Ian; Roberts, Marilyn

    2001-01-01

    Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century. PMID:11381101

  3. RECENT ADVANCES IN ARSENIC CARCINOGENESIS: MODES OF ACTION, ANIMAL MODEL SYSTEMS AND METHYLATED ARSENIC METABOLITES

    Science.gov (United States)

    Abstract: Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer -skin, lung, urinary bladder, liver and kidney. Tumors can be produced from eit...

  4. Tribendimidine: Mode of Action and nAChR Subtype Selectivity in Ascaris and Oesophagostomum

    Science.gov (United States)

    Robertson, Alan P.; Puttachary, Sreekanth; Buxton, Samuel K.; Martin, Richard J.

    2015-01-01

    The cholinergic class of anthelmintic drugs is used for the control of parasitic nematodes. One of this class of drugs, tribendimidine (a symmetrical diamidine derivative, of amidantel), was developed in China for use in humans in the mid-1980s. It has a broader-spectrum anthelmintic action against soil-transmitted helminthiasis than other cholinergic anthelmintics, and is effective against hookworm, pinworms, roundworms, and Strongyloides and flatworm of humans. Although molecular studies on C. elegans suggest that tribendimidine is a cholinergic agonist that is selective for the same nematode muscle nAChR as levamisole, no direct electrophysiological observations in nematode parasites have been made to test this hypothesis. Also the hypothesis that levamisole and tribendimine act on the same receptor, does not explain why tribendimidine is effective against some nematode parasites when levamisole is not. Here we examine the effects of tribendimidine on the electrophysiology and contraction of Ascaris suum body muscle and show that tribendimidine produces depolarization antagonized by the nicotinic antagonist mecamylamine, and that tribendimidine is an agonist of muscle nAChRs of parasitic nematodes. Further pharmacological characterization of the nAChRs activated by tribendimidine in our Ascaris muscle contraction assay shows that tribendimidine is not selective for the same receptor subtypes as levamisole, and that tribendimidine is more selective for the B-subtype than the L-subtype of nAChR. In addition, larval migration inhibition assays with levamisole-resistant Oesophagostomum dentatum isolates show that tribendimidine is as active on a levamisole-resistant isolate as on a levamisole-sensitive isolate, suggesting that the selectivity for levamisole and tribendimidine is not the same. It is concluded that tribendimidine can activate a different population of nematode parasite nAChRs than levamisole, and is more like bephenium. The different nAChR subtype selectivity of tribendimidine may explain why the spectrum of action of tribendimidine is different to that of other cholinergic anthelmintics like levamisole. PMID:25679515

  5. Mode of action of LciA, the lactococcin A immunity protein

    NARCIS (Netherlands)

    Venema, K.; Haverkort, R.E.; Abee, T.; Haandrikman, A.J.; Leenhouts, K.J.; Leij, L. de; Venema, G.; Kok, J.

    1994-01-01

    Monoclonal antibodies were raised against a fusion between the Escherichia coli maltose-binding protein and LciA, the immunity protein that protects Lactococcus lactis against the effects of the bacteriocin lactococcin A. One of the antibodies directed against the LciA moiety of the fusion protein

  6. Tribendimidine: mode of action and nAChR subtype selectivity in Ascaris and Oesophagostomum.

    Directory of Open Access Journals (Sweden)

    Alan P Robertson

    2015-02-01

    Full Text Available The cholinergic class of anthelmintic drugs is used for the control of parasitic nematodes. One of this class of drugs, tribendimidine (a symmetrical diamidine derivative, of amidantel, was developed in China for use in humans in the mid-1980s. It has a broader-spectrum anthelmintic action against soil-transmitted helminthiasis than other cholinergic anthelmintics, and is effective against hookworm, pinworms, roundworms, and Strongyloides and flatworm of humans. Although molecular studies on C. elegans suggest that tribendimidine is a cholinergic agonist that is selective for the same nematode muscle nAChR as levamisole, no direct electrophysiological observations in nematode parasites have been made to test this hypothesis. Also the hypothesis that levamisole and tribendimine act on the same receptor, does not explain why tribendimidine is effective against some nematode parasites when levamisole is not. Here we examine the effects of tribendimidine on the electrophysiology and contraction of Ascaris suum body muscle and show that tribendimidine produces depolarization antagonized by the nicotinic antagonist mecamylamine, and that tribendimidine is an agonist of muscle nAChRs of parasitic nematodes. Further pharmacological characterization of the nAChRs activated by tribendimidine in our Ascaris muscle contraction assay shows that tribendimidine is not selective for the same receptor subtypes as levamisole, and that tribendimidine is more selective for the B-subtype than the L-subtype of nAChR. In addition, larval migration inhibition assays with levamisole-resistant Oesophagostomum dentatum isolates show that tribendimidine is as active on a levamisole-resistant isolate as on a levamisole-sensitive isolate, suggesting that the selectivity for levamisole and tribendimidine is not the same. It is concluded that tribendimidine can activate a different population of nematode parasite nAChRs than levamisole, and is more like bephenium. The different nAChR subtype selectivity of tribendimidine may explain why the spectrum of action of tribendimidine is different to that of other cholinergic anthelmintics like levamisole.

  7. Bioefficacy and mode-of-action of some limonoids of salannin group ...

    Indian Academy of Sciences (India)

    In nutritional assays, all three compounds reduced growth and consumption when fed to larvae without any effect on efficiency of conversion of ingested food (ECI), suggesting antifeedant activity alone. No toxicity was observed nor was there any significant affect on nutritional indices following topical application, further ...

  8. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    considerably among subjects. The dose of verapamil used for cluster headache is approximately double the dose used in cardiovascular disease, most likely because verapamil is a substrate for the efflux transporter P-glycoprotein in the blood-brain barrier. The access of verapamil to the central nervous system......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...

  9. Understanding the Biosynthesis SF2575: A Potent Antitumor Compound With Novel Modes of Action

    Science.gov (United States)

    2009-09-01

    the biosynthesis of siderophores yersinobactin33 and mycobactin34, 35. SsfH was found to be homologous to the salicylate synthase genes Irp933 and... Microbial secondary metabolites: biosynthesis, genetics and regulation, Martin, J. F., Ed. Research Signpost: Lucknow, India, 2002; pp 141. 12

  10. Mode of Action of the Immunostimulatory Effect of Collagen from Jellyfish

    National Research Council Canada - National Science Library

    NISHIMOTO, Sogo; GOTO, Yoko; MORISHIGE, Hitoshi; SHIRAISHI, Ryusuke; DOI, Mikiharu; AKIYAMA, Koichi; YAMAUCHI, Satoshi; SUGAHARA, Takuya

    2008-01-01

    We have previously demonstrated that collagen from jellyfish simulated immunoglobulin and cytokine production by human-human hybridoma line HB4C5 cells and by human peripheral blood lymphocytes (hPBL...

  11. Prion protein-specific antibodies-development, modes of action and therapeutics application.

    Science.gov (United States)

    Rovis, Tihana Lenac; Legname, Giuseppe

    2014-10-01

    Prion diseases or Transmissible Spongiform Encephalopathies (TSEs) are lethal neurodegenerative disorders involving the misfolding of the host encoded cellular prion protein, PrPC. This physiological form of the protein is expressed throughout the body, and it reaches the highest levels in the central nervous system where the pathology occurs. The conversion into the pathogenic isoform denoted as prion or PrPSc is the key event in prion disorders. Prominent candidates for the treatment of prion diseases are antibodies and their derivatives. Anti-PrPC antibodies are able to clear PrPSc from cell culture of infected cells. Furthermore, application of anti-PrPC antibodies suppresses prion replication in experimental animal models. Major drawbacks of immunotherapy are immune tolerance, the risks of neurotoxic side effects, limited ability of compounds to cross the blood-brain barrier and their unfavorable pharmacokinetic. The focus of this review is to recapitulate the current understanding of the molecular mechanisms for antibody mediated anti-prion activity. Although relevant for designing immunotherapeutic tools, the characterization of key antibody parameters shaping the molecular mechanism of the PrPC to PrPSc conversion remains elusive. Moreover, this review illustrates the various attempts towards the development of anti-PrP antibody compounds and discusses therapeutic candidates that modulate PrP expression.

  12. Mesenchymal Stem Cell Therapy for Inflammatory Skin Diseases: Clinical Potential and Mode of Action.

    Science.gov (United States)

    Shin, Tae-Hoon; Kim, Hyung-Sik; Choi, Soon Won; Kang, Kyung-Sun

    2017-01-25

    Inflammatory skin disorders that cause serious deterioration of the quality of life have become one of the major public concerns. Despite their significance, there is no fundamental cure to date. Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties which make them a promising tool for the treatment of various inflammatory diseases. Our recent preclinical and clinical studies have shown that MSCs can be successfully used for the treatment of atopic dermatitis (AD), one of the major inflammatory skin diseases. This observation along with similar reports from other groups revealed the efficacy and underlying mechanisms of MSCs in inflammatory dermatosis. In addition, it has been proposed that cell priming or gene transduction can be novel strategies for the development of next-generation high-efficacy MSCs for treating inflammatory skin diseases. We discuss here existing evidence that demonstrates the regulatory properties of MSCs on immune responses under inflammatory conditions.

  13. Metabolism, Mass Spectral Analysis and Mode of Action of Trichothecene Mycotoxins

    Science.gov (United States)

    1988-10-12

    trintestinal tract, thymus and myocardium. Myocardial hemorrhage ,as severe and transmural , and may be of diagnostic significance. The major... extensive to diffuse involvement of both ventricles and atria. Lymphoid necrosis was severe in the cortex of the thymus and was often accompanied by...locally extensive hemorrhage. There was moderate necrosis of lymphocytes in the cortex and paracortex of lymph nodes, in the periphery of Peyer’s patches nf

  14. Biological control of Pythium aphanidermatum in soilless systems : selection of biocontrol agents and modes of action

    NARCIS (Netherlands)

    Folman, L.B.

    2003-01-01

    De schimmel Pythium aphanidermatum veroorzaakt wortelrot in o.a. komkommer en is een belangrijke ziekteverwekker in de moderne glastuinbouw. Bestrijdingsmiddelen tegen Pythium zijn verboden. Biologische bestrijding met antagonistische bacteriën is een veelbelovend alternatief. Deze antagonisten

  15. Genomic comparisons of two Bacillus subtilis biocontrol strains with different modes of actions

    Science.gov (United States)

    Bacillus subtilis strains AS 43.3 and OH131.1 were isolated from wheat anthers and shown to be efficacious in managing Fusarium head blight in greenhouse and some field trials. Chemical analysis of the cell-free culture supernatant identified B. subtilis strain AS 43.3 to be a potent producer of the...

  16. Characterization and mode of action of enzymes degrading galactan structures of arabinogalactans

    NARCIS (Netherlands)

    Vis, van de J.W.

    1994-01-01

    Agricultural biomass consisting mainly of cellulose, hemicellulose and lignin, is a renewable source of fuels and chemicals. An interesting option is enzymic conversion of biomass to readily usable material. To improve the overall economics of enzymic conversion of biomass not only

  17. Animal Studies in the Mode of Action of Agents, That Are Antitransformers in Cell Cultures.

    Science.gov (United States)

    1987-10-28

    significant difference An aspect of radiocrotection 2-MBA on the immunesystem during radiation therapy see enclosure 4. In t e long term experiment...0.000125M NAD and then incubated at 37 C -or 30 min. The reaction was stopoed by the addition of 40% oerchloric acid (final concentration 2C%) in the cold ...addition of excess cold th- miJine, me cells washed several times and fixed in icecold :ietnanol-acetic acid (3:1). Autoradiocrams were oreoared by 0oda

  18. Antibacterial prenylated isoflavonoids and stilbenoids : quantitative structure-activity relationships and mode of action

    NARCIS (Netherlands)

    Araya-Cloutier, Carla

    2017-01-01

    Prenylated phenolic compounds, i.e. those bearing a C5-isoprenoid  (prenyl) substituent, are abundant in plants from the Fabaceae (legume) family and are potential natural antibacterial agents against resistant pathogenic bacteria. To understand the antibacterial properties of these compounds,

  19. How-To-Do-It: Glyphosate: Herbicidal Effects, Mode of Action and Degradation in Soil.

    Science.gov (United States)

    Kafarski, Pawel; And Others

    1988-01-01

    Describes the usefulness of glyphosate for a demonstration of its herbicidal properties. Includes a list of the materials, preparation of solutions, procedures, data collection and analysis for three activities involving this chemical. (CW)

  20. The effects and mode of action of biochar on the degradation of methyl isothiocyanate in soil.

    Science.gov (United States)

    Fang, Wensheng; Wang, Qiuxia; Han, Dawei; Liu, Pengfei; Huang, Bin; Yan, Dongdong; Ouyang, Canbin; Li, Yuan; Cao, Aocheng

    2016-09-15

    Biochar is used as a new type of fertilizer in agriculture; however, its effect on the fate of fumigants in soil is not fully understood. The objective of this study was to investigate the effects of biochar on methyl isothiocyanate (MITC) degradation in soil in laboratory incubation experiments, including the effects of biochar composition, amendment rate, moisture, temperature, soil sterilization and soil type. The dissipation pathways of MITC in biochars included adsorption and chemical degradation. The adsorption of MITC by biochars was positively correlated with the specific surface area (SSA) of the biochar. Biochar with a high SSA and low H/C value (such as biochar type BC-1) reduced MITC degradation in soil substantially; following BC-1 amendment, the degradation rate was 73.9% slower than in unamended soil. The degradation of MITC was positively correlated with the H/C value of biochar, and MITC degradation in soil increased 2.2-31.1 times following amendment with biochars with higher H/C values (e.g. biochar types BC-3-6). The biochar with the lowest organic matter and low H/C value did not affect the fate of MITC in soil. Biochars affect abiotic degradation processes more than biodegradation. When soil samples had a higher water content (>10%), higher temperature (40°C), and lower organic matter, the addition of BC-1 biochar reduced MITC degradation substantially; and this did not change significantly when the amendment rate increased. However, BC-4 biochar accelerated MITC degradation with increasing amendment rate, increasing temperature, and decreasing soil water content. The differences in degradation rates due to soil type were minimized by amendment with BC-4, but significant differences in BC-1. The results showed that the rational use of biochar has the potential to reduce MITC emission by accelerated degradation and adsorption. Copyright © 2016 Elsevier B.V. All rights reserved.