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

  1. The Key Events Dose-Response Framework: A cross-Disciplinary Mode-of-Action Based Approach to Examining Does-Response and Thresholds

    Science.gov (United States)

    the ILSI Research Foundation conveded a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categoreis of bioactive agents: food allergens, nutrients, pathogenic microorganisms, and ...

  2. The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

    Science.gov (United States)

    Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

    2009-09-01

    The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

  3. Innovative mode of action based in vitro assays for detection of marine neurotoxins

    NARCIS (Netherlands)

    Nicolas, J.A.Y.

    2015-01-01

    Innovative mode of action based in vitro assays for detection of marine neurotoxins

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

    Marine biotoxins are naturally occurring compounds produced by particular phytoplankton species. These toxins often accumulate in

  4. 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…

  5. 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.

  6. 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.

  7. Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

    Science.gov (United States)

    Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

    2010-09-17

    Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. 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.

  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. Evolved pesticide tolerance in amphibians: Predicting mechanisms based on pesticide novelty and mode of action

    International Nuclear Information System (INIS)

    Hua, Jessica; Jones, Devin K.; Mattes, Brian M.; Cothran, Rickey D.; Relyea, Rick A.; Hoverman, Jason T.

    2015-01-01

    We examined 10 wood frog populations distributed along an agricultural gradient for their tolerance to six pesticides (carbaryl, malathion, cypermethrin, permethrin, imidacloprid, and thiamethoxam) that differed in date of first registration (pesticide novelty) and mode-of-action (MOA). Our goals were to assess whether: 1) tolerance was correlated with distance to agriculture for each pesticide, 2) pesticide novelty predicted the likelihood of evolved tolerance, and 3) populations display cross-tolerance between pesticides that share and differ in MOA. Wood frog populations located close to agriculture were more tolerant to carbaryl and malathion than populations far from agriculture. Moreover, the strength of the relationship between distance to agriculture and tolerance was stronger for older pesticides compared to newer pesticides. Finally, we found evidence for cross-tolerance between carbaryl and malathion (two pesticides that share MOA). This study provides one of the most comprehensive approaches for understanding patterns of evolved tolerance in non-pest species. - Highlights: • We explored patterns of tolerance to six insecticides across 10 wood frog populations. • We found evidence that wood frogs have evolved tolerance to carbaryl and malathion. • The likelihood of evolved tolerance was stronger for older compared to newer pesticides. • We found evidence for cross-tolerance between carbaryl and malathion. • This is one of the most comprehensive approaches studying evolved tolerance in a non-pest species. - Using 10 wood frog populations, we detected evidence for evolved tolerance, found that the evolved tolerance depends on insecticide novelty, and found evidence for cross-tolerance.

  12. A cross-disciplinary introduction to quantum annealing-based algorithms

    Science.gov (United States)

    Venegas-Andraca, Salvador E.; Cruz-Santos, William; McGeoch, Catherine; Lanzagorta, Marco

    2018-04-01

    A central goal in quantum computing is the development of quantum hardware and quantum algorithms in order to analyse challenging scientific and engineering problems. Research in quantum computation involves contributions from both physics and computer science; hence this article presents a concise introduction to basic concepts from both fields that are used in annealing-based quantum computation, an alternative to the more familiar quantum gate model. We introduce some concepts from computer science required to define difficult computational problems and to realise the potential relevance of quantum algorithms to find novel solutions to those problems. We introduce the structure of quantum annealing-based algorithms as well as two examples of this kind of algorithms for solving instances of the max-SAT and Minimum Multicut problems. An overview of the quantum annealing systems manufactured by D-Wave Systems is also presented.

  13. 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

    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...... support the process of developing generic competences and are preparing the students to become professional engineers. For the future teaching of the course we have some suggestions for improvements: • Include peer-work as a learning objective and specify rubrics of how to give feedback to make it more...... work prior to and after the field work. The students represent a heterogeneous group of nationalities, previous experiences and scientific subjects. It was clearly seen by the learning outcome and assessment that students who used the offered feedback options during the course actively were more...

  14. 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.

  15. 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.

  16. Creating Cross-disciplinary Courses.

    Science.gov (United States)

    Reynolds, Elaine R

    2012-01-01

    Because of its focus on the biological underpinnings of action and behavior, neuroscience intersects with many fields of human endeavor. Some of these cross-disciplinary intersections have been long standing, while others, such as neurotheology or neuroeconomics, are more recently formed fields. Many undergraduate institutions have sought to include cross-disciplinary courses in their curriculum because this style of pedagogy is often seen as applicable to real world problems. However, it can be difficult for faculty with specialized training within their discipline to expand beyond their own fields to offer cross-disciplinary courses. I have been creating a series of multi- or cross-disciplinary courses and have found some strategies that have helped me successfully teach these classes. I will discuss general strategies and tools in developing these types of courses including: 1) creating mixed experience classrooms of students and contributing faculty 2) finding the right tools that will allow you to teach to a mixed population without prerequisites 3) examining the topic using multiple disciplinary perspectives 4) feeding off student experience and interest 5) assessing the impact of these courses on student outcomes and your neuroscience program. This last tool in particular is important in establishing the validity of this type of teaching for neuroscience students and the general student population.

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

    International Nuclear Information System (INIS)

    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.

    2015-01-01

    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 24 h and 48 h 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. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Diffusion-Based Recommendation in Collaborative Tagging Systems

    Science.gov (United States)

    Shang, Ming-Sheng; Zhang, Zi-Ke

    2009-11-01

    Recently, collaborative tagging systems have attracted more and more attention and have been widely applied in web systems. Tags provide highly abstracted information about personal preferences and item content, and therefore have the potential to help in improving better personalized recommendations. We propose a diffusion-based recommendation algorithm considering the personal vocabulary and evaluate it in a real-world dataset: Del.icio.us. Experimental results demonstrate that the usage of tag information can significantly improve the accuracy of personalized recommendations.

  20. Cross-disciplinary consumer citizenship education

    DEFF Research Database (Denmark)

    Nielsen, Sanne Schnell; Gottschau, Jette

    2005-01-01

    and common everyday experience for both students and pupils: the living conditions, lifestyle choices and consumer behaviour connected to a lunchtime meal. The overall aim of the workshop is to develop transferable knowledge, attitudes and skills among the students. The students are supposed to apply......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...... and consumer education, along with pedagogical issues, with the aim of developing a holistic, integrated approach to consumer citizenship education. The workshop concept is based on the “IVAC” (Investigation, Visions, Actions & Changes) model (Jensen 1997). As our point of departure, we take a practical...

  1. 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.

  2. 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,

  3. Case study: an evaluation of the human relevance of the synthetic pyrethroid metofluthrin-induced liver tumors in rats based on mode of action.

    Science.gov (United States)

    Yamada, Tomoya; Uwagawa, Satoshi; Okuno, Yasuyoshi; Cohen, Samuel M; Kaneko, Hideo

    2009-03-01

    In recent years, mode of action (MOA) frameworks have been developed through the International Life Sciences Institute Risk Science Institute and the International Programme on Chemical Safety, including an evaluation of the human relevance of the animal MOA data. In the present paper, the MOA for rat liver tumors induced by Metofluthrin is first analyzed through this framework based on data from studies on Metofluthrin and information on related chemicals from the literature. The human relevance of the rat liver carcinogenic response is then discussed based upon the human relevance framework. Two-year treatment with high dose of Metofluthrin produced hepatocellular tumors in both sexes of the Wistar rats. Metofluthrin induced CYP2B (increased smooth endoplasmic reticulum), resulted in increased liver weights which were associated with centrilobular hepatocyte hypertrophy, and induction of increased hepatocellular DNA replications. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. Furthermore, CYP2B induction by Metofluthrin was shown to involve activation of the constitutive androstane receptor in rat hepatocytes. Based on the evidence, including a comparison with the results with another chemical, phenobarbital, acting by a similar MOA, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans.

  4. iTRAQ-based proteomic analysis of LI-F type peptides produced by Paenibacillus polymyxa JSa-9 mode of action against Bacillus cereus.

    Science.gov (United States)

    Han, Jinzhi; Gao, Peng; Zhao, Shengming; Bie, Xiaomei; Lu, Zhaoxin; Zhang, Chong; Lv, Fengxia

    2017-01-06

    ) indirect effects on the same pathways through the accumulation of ROS and the consequent impairment of cellular functions, resulting from downregulation of antioxidant proteins, especially CAT and SOD. The mode of action of LI-F type antimicrobial peptides (AMP-jsa9) against B. cereus was elucidated at the proteomic level. Two pathways of AMP-jsa9 action upon B. cereus cells were identified and the mechanism of bleb formation on the surfaces of bacterial cells was predicted based on the results of ultrastructural observation and proteomic analysis. These results are helpful in understanding the mechanism of LI-F type peptides and in providing the theoretical base for applying AMP-jsa9 or its analogs to combat Gram-positive pathogenic bacteria in the food and feed industries. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Cross-Disciplinary Ethics Education in MBA Programs

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich; Schedel, Ingo

    2013-01-01

    This research-based essay offers a cross-disciplinary examination of ethics education in MBA programs. Based on data underlying the Beyond Grey Pinstripes (BGP) survey we find: that business schools doubled the number of ethics-related courses in different disciplines between 2005 and 2009......: 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...... to fully integrate ethics into the curriculum. We suggest that more effective ethics education requires structural changes to the curriculum, in particular more mandatory ethics courses and a stronger integration of ethics-related debates into disciplines like finance and accounting....

  6. Cross-Disciplinary Ethics Education in MBA Programs

    DEFF Research Database (Denmark)

    Rasche, Andreas; Gilbert, Dirk Ulrich; Schedel, Ingo

    This research-based essay offers a cross-disciplinary examination of ethics education in MBA programs. Based on data underlying the Beyond Grey Pinstripes (BGP) survey we find: that business schools doubled the number of ethics-related courses in different disciplines between 2005 and 2009......: 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...... to fully integrate ethics into the curriculum. We suggest that more effective ethics education requires structural changes to the curriculum, in particular more mandatory ethics courses and a stronger integration of ethics-related debates into disciplines like finance and accounting....

  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. Concept similarity in publications precedes cross-disciplinary collaboration.

    Science.gov (United States)

    Post, Andrew R; Harrison, James H

    2008-11-06

    Innovative science frequently occurs as a result of cross-disciplinary collaboration, the importance of which is reflected by recent NIH funding initiatives that promote communication and collaboration. If shared research interests between collaborators are important for the formation of collaborations,methods for identifying these shared interests across scientific domains could potentially reveal new and useful collaboration opportunities. MEDLINE represents a comprehensive database of collaborations and research interests, as reflected by article co-authors and concept content. We analyzed six years of citations using information retrieval based methods to compute articles conceptual similarity, and found that articles by basic and clinical scientists who later collaborated had significantly higher average similarity than articles by similar scientists who did not collaborate.Refinement of these methods and characterization of found conceptual overlaps could allow automated discovery of collaboration opportunities that are currently missed.

  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. Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole

    NARCIS (Netherlands)

    Alajlouni, A.M.; Al-Malahmeh, A.J.; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, A.E.M.F.; Al-Subeihi, A.A.A.; Vervoort, Jacques; Rietjens, I.M.C.M.

    2016-01-01

    The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about

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

    African Journals Online (AJOL)

    Innovative sport technology through cross-disciplinary research: Future of sport ... South African Journal for Research in Sport, Physical Education and Recreation ... of the advantages and disadvantages of innovative sport technology brought ...

  12. Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole.

    Science.gov (United States)

    Alajlouni, Abdalmajeed M; Al Malahmeh, Amer J; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, Ans E M F; Al-Subeihi, Ala A A; Vervoort, Jacques; Rietjens, Ivonne M C M

    2016-03-01

    The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10(-5) mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Understanding of the mode of action of Fe(III)-EDDHA as iron chlorosis corrector based on its photochemical and redox behavior.

    Science.gov (United States)

    Gómez-Gallego, Mar; Pellico, Daniel; Ramírez-López, Pedro; Mancheño, María J; Romano, Santiago; de la Torre, María C; Sierra, Miguel A

    2005-10-07

    The very low reduction potential of the chelate Fe(III)-EDDHA (EDDHA = ethylenediamine N,N'-bis(2-hydroxy)phenylacetic acid) makes it unreactive in photochemically or chemically induced electron transfer processes. The lack of reactivity of this complex toward light invalidates photodegradation as an alternative mechanism for environmental elimination. However, in spite of its low reduction potential, the biological reduction of Fe(III)-EDDHA is very effective. Based on electrochemical measurements, it is proposed that Fe(III)-EDDHA itself is not the substrate of the enzyme ferric chelate reductase. Likely, at the more acidic pH in the vicinity of the roots, the ferric chelate in a closed form (FeL-) could generate a vacant coordination site that leads to an open hexacoordinate species (FeHL) where the reduction of the metal by the enzyme takes place.

  14. Measuring the evolution and output of cross-disciplinary collaborations within the NCI Physical Sciences–Oncology Centers Network

    Science.gov (United States)

    Basner, Jodi E.; Theisz, Katrina I.; Jensen, Unni S.; Jones, C. David; Ponomarev, Ilya; Sulima, Pawel; Jo, Karen; Eljanne, Mariam; Espey, Michael G.; Franca-Koh, Jonathan; Hanlon, Sean E.; Kuhn, Nastaran Z.; Nagahara, Larry A.; Schnell, Joshua D.; Moore, Nicole M.

    2013-01-01

    Development of effective quantitative indicators and methodologies to assess the outcomes of cross-disciplinary collaborative initiatives has the potential to improve scientific program management and scientific output. This article highlights an example of a prospective evaluation that has been developed to monitor and improve progress of the National Cancer Institute Physical Sciences—Oncology Centers (PS-OC) program. Study data, including collaboration information, was captured through progress reports and compiled using the web-based analytic database: Interdisciplinary Team Reporting, Analysis, and Query Resource. Analysis of collaborations was further supported by data from the Thomson Reuters Web of Science database, MEDLINE database, and a web-based survey. Integration of novel and standard data sources was augmented by the development of automated methods to mine investigator pre-award publications, assign investigator disciplines, and distinguish cross-disciplinary publication content. The results highlight increases in cross-disciplinary authorship collaborations from pre- to post-award years among the primary investigators and confirm that a majority of cross-disciplinary collaborations have resulted in publications with cross-disciplinary content that rank in the top third of their field. With these evaluation data, PS-OC Program officials have provided ongoing feedback to participating investigators to improve center productivity and thereby facilitate a more successful initiative. Future analysis will continue to expand these methods and metrics to adapt to new advances in research evaluation and changes in the program. PMID:24808632

  15. Cross-disciplinary research programs at the Cornell TRIGA reactor

    International Nuclear Information System (INIS)

    Clark, D.D.

    1995-01-01

    This paper describes cross-disciplinary research efforts at the Cornell TRIGA reactor. A new graduate laboratory course for nonspecialists was developed which brought in graduate students from many fields, and a weekly or bimonthly nuclear methods seminars are being held to describe research methods, sample preparation, irradiation, etc

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

    DEFF Research Database (Denmark)

    Alrøe, Hugo Fjelsted; Noe, Egon

    2014-01-01

    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...

  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. 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

  19. 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.

  20. 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.

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

    NARCIS (Netherlands)

    Aalst, Susan van

    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

  2. Modes of Action of Microbially-Produced Phytotoxins

    Science.gov (United States)

    Duke, Stephen O.; Dayan, Franck E.

    2011-01-01

    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. PMID:22069756

  3. 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.

  4. 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.

  5. Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol ...

    African Journals Online (AJOL)

    Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol Extract against ... the antibacterial effect of ethanol extract of Mentha arvensis against multi-drug ... Reactive oxygen species (ROS) generation and protein leakage from the ... A. baumannii and acts by inducing lethal cellular damage to the bacterium.

  6. Discovery of new herbicide modes of action with natural phytotoxins

    Science.gov (United States)

    About 20 modes of action (MOAs) are utilized by commercial herbicides, and almost 30 years have passed since the last new MOA was introduced. Rapidly increasing evolution of resistance to herbicides with these MOAs has greatly increased the need for herbicides with new MOAs. Combinatorial chemistry ...

  7. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    Science.gov (United States)

    Waldbusser, George G; Hales, Burke; Langdon, Chris J; Haley, Brian A; Schrader, Paul; Brunner, Elizabeth L; Gray, Matthew W; Miller, Cale A; Gimenez, Iria; Hutchinson, Greg

    2015-01-01

    Ocean acidification (OA) is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4) with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material affected only by

  8. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    Directory of Open Access Journals (Sweden)

    George G Waldbusser

    Full Text Available Ocean acidification (OA is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4 with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. The Science Semester: Cross-Disciplinary Inquiry for Prospective Elementary Teachers

    Science.gov (United States)

    Ford, Danielle J.; Fifield, Steve; Madsen, John; Qian, Xiaoyu

    2013-10-01

    We describe the Science Semester, a semester-long course block that integrates three science courses and a science education methods course for elementary teacher education majors, and examine prospective elementary teachers’ developing conceptions about inquiry, science teaching efficacy, and reflections on learning through inquiry. The Science Semester was designed to provide inquiry-oriented and problem-based learning experiences, opportunities to examine socially relevant issues through cross-disciplinary perspectives, and align with content found in elementary curricula and standards. By the end of the semester, prospective elementary teachers moved from naïve to intermediate understandings of inquiry and significantly increased self-efficacy for science teaching as measured on one subscore of the STEBI-B. Reflecting on the semester, prospective teachers understood and appreciated the goals of the course and the PBL format, but struggled with the open-ended and student-directed elements of the course.

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

    International Nuclear Information System (INIS)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

    2011-01-01

    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. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  15. 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.

  16. 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.

  17. 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.

  18. Omics Methods for Probing the Mode of Action of Natural and Synthetic Phytotoxins

    OpenAIRE

    Duke, Stephen O.; Bajsa, Joanna; Pan, Zhiqiang

    2013-01-01

    For a little over a decade, omics methods (transcriptomics, proteomics, metabolomics, and physionomics) have been used to discover and probe the mode of action of both synthetic and natural phytotoxins. For mode of action discovery, the strategy for each of these approaches is to generate an omics profile for phytotoxins with known molecular targets and to compare this library of responses to the responses of compounds with unknown modes of action. Using more than one omics approach enhances ...

  19. Minireview: Mode of action of meta-diamide insecticides.

    Science.gov (United States)

    Nakao, Toshifumi; Banba, Shinichi

    2015-06-01

    Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor noncompetitive antagonists showing high insecticidal activity against Spodoptera litura. The mode of action of the meta-diamides was demonstrated to be distinct from that of conventional noncompetitive antagonists (NCAs) such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. It was suggested that meta-diamides act at or near G336 in the M3 region of the Drosophila RDL GABA receptor. Although the site of action of the meta-diamides appears to overlap with that of macrocyclic lactones including avermectins and milbemycins, differential effects of mutations on the actions of the meta-diamides and the macrocyclic lactones were observed. Molecular modeling studies revealed that the meta-diamides may bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor better when in the closed state, which is distinct from the NCA-binding site, which is in a channel formed by M2s. In contrast, the macrocyclic lactones were suggested to bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor when in the open state. Furthermore, mechanisms underlying the high selectivity of meta-diamides are discussed. This minireview highlights the unique features of novel meta-diamide insecticides and demonstrates why meta-diamides are anticipated to become prominent insecticides that are effective against pests resistant to cyclodienes and fipronil. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. 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,

  1. 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,

  2. 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

  3. 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

  4. Omics methods for probing the mode of action of natural phytotoxins

    Science.gov (United States)

    For a little over a decade, omics methods (transcriptomics, proteomics, metabolomics, and physionomics) have been used to discover and probe the mode of action of both synthetic and natural phytotoxins. For mode of action discovery, the strategy for each of these approaches is to generate an omics...

  5. Configurable User Interface Framework for Data Discovery in Cross-Disciplinary and Citizen Science

    Science.gov (United States)

    Rozell, E.; Wang, H.; West, P.; Zednik, S.; Fox, P.

    2012-04-01

    Use cases for data discovery and analysis vary widely when looking across disciplines and levels of expertise. Domain experts across disciplines may have a thorough understanding of self-describing data formats, such as netCDF, and the software packages that are compatible. However, they may be unfamiliar with specific vocabulary terms used to describe the data parameters or instrument packages in someone else's collection, which are often useful in data discovery. Citizen scientists may struggle with both expert vocabularies and knowledge of existing tools for analyzing and visualizing data. There are some solutions for each problem individually. For expert vocabularies, semantic technologies like the Resource Description Framework (RDF) have been used to map terms from an expert vocabulary to layperson terminology. For data analysis and visualization, tools can be mapped to data products using semantic technologies as well. This presentation discusses a solution to both problems based on the S2S Framework, a configurable user interface (UI) framework for Web services. S2S unifies the two solutions previously described using a data service abstraction ("search services") and a UI abstraction ("widgets"). Using the OWL Web Ontology Language, S2S defines a vocabulary for describing search services and their outputs, and the compatibility of those outputs with UI widgets. By linking search service outputs to widgets, S2S can automatically compose UIs for search and analysis of data, making it easier for citizen scientists to manipulate data. We have also created Linked Data widgets for S2S, which can leverage distributed RDF resources to present alternative views of expert vocabularies. This presentation covers some examples where we have applied these solutions to improve data discovery for both cross-disciplinary and non-expert users.

  6. Enhancing pressure ulcer prevention using wound dressings: what are the modes of action?

    Science.gov (United States)

    Call, Evan; Pedersen, Justin; Bill, Brian; Black, Joyce; Alves, Paulo; Brindle, C Tod; Dealey, Carol; Santamaria, Nick; Clark, Michael

    2015-08-01

    Recent clinical research has generated interest in the use of sacral wound dressings as preventive devices for patients at risk of ulceration. This study was conducted to identify the modes of action through which dressings can add to pressure ulcer prevention, for example, shear and friction force redistribution and pressure distribution. Bench testing was performed using nine commercially available dressings. The use of dressings can reduce the amplitude of shear stress and friction reaching the skin of patients at risk. They can also effectively redirect these forces to wider areas which minimises the mechanical loads upon skeletal prominences. Dressings can redistribute pressure based upon their effective Poisson ratio and larger deflection areas, providing greater load redistribution. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Clinical Immersion: An Approach for Fostering Cross-disciplinary Communication and Innovation in Nursing and Engineering Students.

    Science.gov (United States)

    Geist, Melissa J; Sanders, Robby; Harris, Kevin; Arce-Trigatti, Andrea; Hitchcock-Cass, Cary

    2018-05-24

    A faculty team from nursing and chemical engineering developed a course that brought together students from each discipline for cross-disciplinary, team-based clinical immersion and collaboration. Health care processes and devices are rapidly changing, and nurses are uniquely positioned to be bedside innovators to improve patient care delivery. During each clinical immersion, the student teams rotated through various hospital units where they identified problems and worked together in the university's makerspace (iMaker Space) to design and build prototypes to improve health outcomes. Data from the Critical thinking Assessment Test provided evidence of gains in critical-thinking and problem-solving skills, while the problems identified in the clinical setting and prototypes developed demonstrated the impact of bringing nursing and engineering students together to design innovations. When challenged to identify authentic problems during their clinical immersion, the teams of nursing and engineering students proposed creative solutions and developed commercially viable prototypes.

  8. 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.

  9. Solving cross-disciplinary problems by mathematical modelling

    Science.gov (United States)

    Panfilov, D. A.; Romanchikov, V. V.; Krupin, K. N.

    2018-03-01

    The article deals with the creation of a human tibia 3D model by means of “Autodesk Revit-2016” PC based on tomogram data. The model was imported into “Lira- SAPR2013 R4” software system. To assess the possibility of education and the nature of bone fracture (and their visualization), the Finite Element Analysis (FEA) method was used. The geometric parameters of the BBK model corresponded to the physical parameters of the individual. The compact plate different thickness is modeled by rigidity properties of the finite elements in accordance with the parameters on the roentgenogram. The BBK model included parameters of the outer compact plate and the spongy substance having a more developed structure of the epiphysic region. In the “Lira-SAPR2013 R4” software system, mathematical modeling of the traumatic effect was carried out and the analysis of the stress-strain state of the finite element model of the tibia was made to assess fracture conditions.

  10. 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.

  11. The Bridge: Experiments in Science and Art, Experiences from the 2017 SciArt Center Cross-Disciplinary Residency Program

    Science.gov (United States)

    Shipman, J. S.; Chalmers, R.; Buntaine, J.

    2017-12-01

    Cross-disciplinary programs create the opportunity to explore new realms for scientists and artists alike. Through the collaborative process, artistic insights enable innovative approaches to emotionally connect to and visualize the world around us. Likewise, engagement across the art-science spectrum can lead to shifts in scientific thinking that create new connections in data and drive discoveries in research. The SciArt Center "The Bridge Residency Program" is a four-month long virtual residency open internationally for professionals in the arts and sciences to facilitate cross-disciplinary work and to bring together like-minded participants. The SciArt Center provides a virtual space to record and showcase the process and products of each collaboration. The work is facilitated with biweekly Skype calls and documented with weekly blog posts. Residents create either digital or physical products and share via video, images, or direct mailing with their collaborators. Past projects have produced call and response discussion, websites, skills and conference presentations, science-art studies, virtual exhibits, art shows, dance performances, and research exchange. Here we present the creative process and outcomes of one of the four collaborative teams selected for the 2017 residency. Jill Shipman, a Ph.D. Candidate in Volcanology who is also active in filmmaking and theatrical productions and Rosemary Chalmers, a UK-based lecturer, concept artist, and illustrator with a specialty in creature design. They were paired together for their shared interest in storytelling, illustration, and unique geological and environmental habitats and the life that occupies them. We will discuss the collaborative project developed by this team during their recent residency and illustrate how a virtual program can bridge the distance between geographical location to foster science and art collaboration. To follow the progress of the residency please visit: http://www.sciartcenter.org/the-bridge.html

  12. Omics methods for probing the mode of action of natural and synthetic phytotoxins.

    Science.gov (United States)

    Duke, Stephen O; Bajsa, Joanna; Pan, Zhiqiang

    2013-02-01

    For a little over a decade, omics methods (transcriptomics, proteomics, metabolomics, and physionomics) have been used to discover and probe the mode of action of both synthetic and natural phytotoxins. For mode of action discovery, the strategy for each of these approaches is to generate an omics profile for phytotoxins with known molecular targets and to compare this library of responses to the responses of compounds with unknown modes of action. Using more than one omics approach enhances the probability of success. Generally, compounds with the same mode of action generate similar responses with a particular omics method. Stress and detoxification responses to phytotoxins can be much clearer than effects directly related to the target site. Clues to new modes of action must be validated with in vitro enzyme effects or genetic approaches. Thus far, the only new phytotoxin target site discovered with omics approaches (metabolomics and physionomics) is that of cinmethylin and structurally related 5-benzyloxymethyl-1,2-isoxazolines. These omics approaches pointed to tyrosine amino-transferase as the target, which was verified by enzyme assays and genetic methods. In addition to being a useful tool of mode of action discovery, omics methods provide detailed information on genetic and biochemical impacts of phytotoxins. Such information can be useful in understanding the full impact of natural phytotoxins in both agricultural and natural ecosystems.

  13. 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

  14. Counselling and knowledge about contraceptive mode of action among married women; a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ciğerli Özlem

    2006-08-01

    Full Text Available Abstract Background Family planning counselling which covers knowledge transfer about contraceptive mode of action, by enabling informed choice, improves compliance to and efficiency of contraceptive methods. The objective of this study was to investigate associations between family planning counselling, counsellor and correct knowledge about mode of action of modern contraceptive methods among married women. Methods For this cross-sectional study, stratified (according to current modern contraceptive method in use random sampling was performed from the registries of two primary health care centres. Main outcomes were; prevalence of family planning counselling, professional background of the counsellor and correct knowledge about mode of action. A semi-structured questionnaire developed by the researchers was applied via face-to-face interview. The answers about mode of action were categorized as correct vs. incorrect by consensus rating. Results Prevalence of counselling and correct knowledge about mode of action was 49.0% and 39.3%, respectively. Higher educated women were significantly more likely to know the mode of action (p p = 0.79. Non-barrier method users were less educated (p = 0.001, more often counselled (60.8% vs. 8.0% and less knowledgeable (p p = 0.021 than counselled condom users. Conclusion The beneficial effect of counselling on knowledge about mode of action of the more complicated, medical (non-barrier contraceptive methods suggests that the use of family planning counselling services in primary health care should be promoted; furthermore, counselling strategies and content should be re-structured for better efficacy.

  15. Trust Management - Building Trust for International Cross Disciplinary Collaboration on Climate Change

    Science.gov (United States)

    Oakley, K. V.; Gurney, R. J.

    2014-12-01

    Successful communication and collaboration entails mutual understanding, and transfer, of information. The risk of misunderstanding and/or miscommunication between collaborating groups is tackled in different ways around the globe; some are well documented whereas others may be unknown outside particular groups, whether defined geographically or by specialism. For example; in some countries legally binding contracts define the terms of collaboration. Some regions place greater emphasis on developing trust relationships, and sometimes an official agreement is implied, such as many electronic data transfers on the web. International collaboration on climate change increasingly involves electronic data exchange (e.g. open access publications, shared documents, data repositories etc.) and with this increased reliance on electronic data a need has arisen for scientists to collaborate both internationally and cross-disciplinarily particularly with information technology and data management specialists. Trust of data and metadata on the internet (e.g. privacy, legitimacy etc.) varies, possibly due to a lack of internationally agreed standards for data governance and management, leaving many national, regional and institutional practices tailored to the needs of that group only. It is proposed that building trust relationships between cross-disciplinary and international groups could help facilitate further communication, understanding and benefits from the relationship, while still maintaining independence as separate groups. Complex international cross-disciplinary group relationship dynamics are not easily mapped and producing a set of trust building rules that can be applied to any current and future collaboration with equal validity may be unfeasible. An alternative to such a set of rules may be found in a Trust Manager, whose role is to improve mutually beneficial knowledge exchange between groups, build trust and increase future collaborative potential. This

  16. Characterization of the mode of action of a potent dengue virus capsid inhibitor.

    Science.gov (United States)

    Scaturro, Pietro; Trist, Iuni Margaret Laura; Paul, David; Kumar, Anil; Acosta, Eliana G; Byrd, Chelsea M; Jordan, Robert; Brancale, Andrea; Bartenschlager, Ralf

    2014-10-01

    Dengue viruses (DV) represent a significant global health burden, with up to 400 million infections every year and around 500,000 infected individuals developing life-threatening disease. In spite of attempts to develop vaccine candidates and antiviral drugs, there is a lack of approved therapeutics for the treatment of DV infection. We have previously reported the identification of ST-148, a small-molecule inhibitor exhibiting broad and potent antiviral activity against DV in vitro and in vivo (C. M. Byrd et al., Antimicrob. Agents Chemother. 57:15-25, 2013, doi:10 .1128/AAC.01429-12). In the present study, we investigated the mode of action of this promising compound by using a combination of biochemical, virological, and imaging-based techniques. We confirmed that ST-148 targets the capsid protein and obtained evidence of bimodal antiviral activity affecting both assembly/release and entry of infectious DV particles. Importantly, by using a robust bioluminescence resonance energy transfer-based assay, we observed an ST-148-dependent increase of capsid self-interaction. These results were corroborated by molecular modeling studies that also revealed a plausible model for compound binding to capsid protein and inhibition by a distinct resistance mutation. These results suggest that ST-148-enhanced capsid protein self-interaction perturbs assembly and disassembly of DV nucleocapsids, probably by inducing structural rigidity. Thus, as previously reported for other enveloped viruses, stabilization of capsid protein structure is an attractive therapeutic concept that also is applicable to flaviviruses. Dengue viruses are arthropod-borne viruses representing a significant global health burden. They infect up to 400 million people and are endemic to subtropical and tropical areas of the world. Currently, there are neither vaccines nor approved therapeutics for the prophylaxis or treatment of DV infections, respectively. This study reports the characterization of the

  17. Minimum datasets to establish a CAR-mediated mode of action for rodent liver tumors.

    Science.gov (United States)

    Peffer, Richard C; LeBaron, Matthew J; Battalora, Michael; Bomann, Werner H; Werner, Christoph; Aggarwal, Manoj; Rowe, Rocky R; Tinwell, Helen

    2018-07-01

    Methods for investigating the Mode of Action (MoA) for rodent liver tumors via constitutive androstane receptor (CAR) activation are outlined here, based on current scientific knowledge about CAR and feedback from regulatory agencies globally. The key events (i.e., CAR activation, altered gene expression, cell proliferation, altered foci and increased adenomas/carcinomas) can be demonstrated by measuring a combination of key events and associative events that are markers for the key events. For crop protection products, a primary dataset typically should include a short-term study in the species/strain that showed the tumor response at dose levels that bracket the tumorigenic and non-tumorigenic dose levels. The dataset may vary depending on the species and the test compound. As examples, Case Studies with nitrapyrin (in mice) and metofluthrin (in rats) are described. Based on qualitative differences between the species, the key events leading to tumors in mice or rats by this MoA are not operative in humans. In the future, newer approaches such as a CAR biomarker signature approach and/or in vitro CAR3 reporter assays for mouse, rat and human CAR may eventually be used to demonstrate a CAR MoA is operative, without the need for extensive additional studies in laboratory animals. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. 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

  20. Furocoumarins, biophysical investigations on their modes of action

    International Nuclear Information System (INIS)

    Kittler, L.; Loeber, G.

    1983-01-01

    Investigation of the combined effect of furocoumarins and ultraviolet light of 365 nm wavelength (UV light) on cellular constituents are important for they have clearly increased the knowledge on basic processes involved in PUVA therapy. Studies of the action on nucleic acids both in isolated state and in situ led to the following conclusions, when 8-methoxypsoralen (8-MOP) and angelicin were used as sensitizers: Crosslinking between the drug and the nucleic acid bases is preferred in A-T rich or A-U rich sites with the nucleic acid being in B conformation. In situ crosslinked DNA does not influence the adsorption of phage lambda on the surface of E. coli. There are probably three types of furocoumarins mediated crosslinks inside the phage: Type I, corresponding to crosslinking between complementary strands of the DNA duplex, type II, corresponding to crosslinks between adjacent sites in the folded DNA structure (hair pin crosslinks) and DNA protein crosslinks. Type I does not prevent the DNA from getting into the host cell, while the two latter do. PUVA treatment of human lymphocyte cultures is manifested by chromosomal aberrations such as premature centromere division and major coiling. However, treatment with 8-MOP or UV light alone do produce the same kind of aberrations. Under the action of UV light, 8-MOP or trimethylpsoralen become covalently bound to unsaturated fatty acids. The photoreaction preceeds without essential contribution of singlet oxygen and hydroperoxides. (author)

  1. 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.

  2. Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance.

    Science.gov (United States)

    Eltahla, Auda A; Luciani, Fabio; White, Peter A; Lloyd, Andrew R; Bull, Rowena A

    2015-09-29

    The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development, and direct-acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.

  3. Proteomic and metallomic strategies for understanding the mode of action of anticancer metallodrugs.

    Science.gov (United States)

    Gabbiani, Chiara; Magherini, Francesca; Modesti, Alessandra; Messori, Luigi

    2010-05-01

    Since the discovery of cisplatin and its introduction in the clinics, metal compounds have been intensely investigated in view of their possible application in cancer therapy. In this frame, a deeper understanding of their mode of action, still rather obscure, might turn crucial for the design and the obtainment of new and better anticancer agents. Due to the extreme complexity of the biological systems, it is now widely accepted that innovative and information-rich methods are absolutely needed to afford such a goal. Recently, both proteomic and metallomic strategies were successfully implemented for the elucidation of specific mechanistic features of anticancer metallodrugs within an innovative "Systems Biology" perspective. Particular attention was paid to the following issues: i) proteomic studies of the molecular basis of platinum resistance; ii) proteomic analysis of cellular responses to cytotoxic metallodrugs; iii) metallomic studies of the transformation and fate of metallodrugs in cellular systems. Notably, those pioneering studies, that are reviewed here, allowed a significant progress in the understanding of the molecular mechanisms of metal based drugs at the cellular level. A further extension of those studies and a closer integration of proteomic and metallomic strategies and technologies might realistically lead to rapid and significant advancements in the mechanistic knowledge of anticancer metallodrugs.

  4. 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 targets/mode-of-action by application of systems biology technologies J BECKER, L MTWISHA, B CRAMPTON AND D MANCAMA CSIR Biosciences, PO Box 395, Pretoria, 0001, South Africa Email: JBecker@csir.co.za – www.csir.co.za INTRODUCTION Malaria is one... The objective of this study was to use systems biology tools to unravel the drug target/mode-of-action (MoA) of an antimalarial drug (cyclohexylamine) with a known drug target/MoA, by analysing differential expression profiles of drug treated vs untreated...

  5. A Cross-Disciplinary Successful Aging Intervention and Evaluation: Comparison of Person-to-Person and Digital-Assisted Approaches

    Directory of Open Access Journals (Sweden)

    Hui-Chuan Hsu

    2018-05-01

    Full Text Available Background: Successful aging has been the paradigm of old-age life. The purpose of this study was to implement and evaluate a cross-disciplinary intervention program using two approaches for community-based older adults in Taichung, Taiwan. Methods: The content of the intervention included successful aging concepts and preparation, physical activity, chronic disease and health management, dietary and nutrition information, cognitive training, emotional awareness and coping skills, family relationship and resilience, legal concepts regarding financial protection, and Internet use. The traditional person-to-person (P2P intervention approach was implemented among participants at urban centers, and the personal-and-digital (P&D intervention approach was implemented among participants at rural centers; before the P&D group received the intervention, participants were assessed as the control group for comparison. Results: Healthy behavior and nutrition improved for the P2P group, although not significantly. Strategies for adapting to old age and reducing ineffective coping were significantly improved in the P2P group. The ability to search for health information improved in the P&D group, and knowledge of finance-related law increased in the P2P group. Conclusion: A continuous, well-designed and evidence-based intervention program is beneficial for improving the health of older adults, or at least delaying its decline.

  6. Spontaneous bacteriocin resistance in Listeria monocytogenes as a susceptibility screen for identifying different mechanisms of resistance and modes of action by bacteriocins of lactic acid bacteria.

    Science.gov (United States)

    Macwana, Sunita; Muriana, Peter M

    2012-01-01

    A practical system was devised for grouping bacteriocins of lactic acid bacteria (LAB) based on mode of action as determined by changes in inhibitory activity to spontaneously-acquired bacteriocin resistance (Bac(R)). Wild type Listeria monocytogenes 39-2 was sensitive to five bacteriocins produced by 3 genera of LAB: pediocin PA-1 and pediocin Bac3 (Pediococcus), lacticin FS97 and lacticin FS56 (Lactococcus), and curvaticin FS47 (Lactobacillus). A spontaneous Bac(R) derivative of L. monocytogenes 39-2 obtained by selective recovery against lacticin FS56 provided complete resistance to the bacteriocin made by Lactococcus lactis FS56. The lacticin FS56-resistant strain of L. monocyotgenes 39-2 was also cross-resistant to curvaticin FS47 and pediocin PA-1, but not to lacticin FS97 or pediocin Bac3. The same pattern of cross-resistance was also observed with Bac(R) isolates obtained with L. monocytogenes Scott A-2. A spontaneous mutation that renders a strain cross-resistant to different bacteriocins indicates that they share a common mechanism of resistance due to similar modes of action of the bacteriocins. Spontaneous resistance was acquired to other bacteriocins (in aggregate) by following the same procedure against which the Bac(R) strain was still sensitive. In subsequent challenge assays, mixtures of bacteriocins of different modes of action provided greater inhibition than mixtures of bacteriocins of the same mode of action (as determined by our screening method). This study identifies a methodical approach to classify bacteriocins into functional groups based on mechanism of resistance (i.e., mode of action) that could be used for identifying the best mixture of bacteriocins for use as biopreservatives. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. 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

  8. An evaluation of the mode of action framework for mutagenic carcinogens: Chromium (VI): SOT.

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  9. An evaluation of the mode of action framework for mutagenic carcinogens: chromium (VI)

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  10. 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

  11. 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

    the biosynthesis rate of macromolecules (e.g., DNA, RNA, protein, and cell wall) and the cytoplasmic membrane proton motive force (PMF) energy can help to unravel the diverse modes of action of AMPs. Here, we present an overview of macromolecule biosynthesis rate measurement and fluorescence spectroscopy methods...

  12. Tandem mass spectrometric analysis of Aspergillus niger pectin methylesterase: mode of action on fully methylesterified oligogalacturonates

    NARCIS (Netherlands)

    Kester, H.C.M.; Esteban Warren, M.; Orlando, R.; Benen, J.A.E.; Bergmann, C.; Visser, J.

    2000-01-01

    The substrate specificity and the mode of action of Aspergillus niger pectin methylesterase (PME) was determined using both fully methyl-esterified oligogalacturonates with degrees of polymerization (DP) 2–6 and chemically synthesized monomethyl trigalacturonates. The enzymic activity on the

  13. 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

  14. The “Shawshank Trail”: A Cross Disciplinary Study in Film Induced Tourism and Fan Culture

    Directory of Open Access Journals (Sweden)

    Richard Roberson

    2015-03-01

    Full Text Available Tourism, as a sustainable means of economic development, has attracted a considerable amount of attention from municipalities seeking to better understand their available development options. Film induced tourism has seen appreciable growth and represents a considerable opportunity for many communities to use filming locations seen in popular movies and/or television to draw additional visitors. These opportunities create an increasing need for communities and the organizers of events to better understand their attendees, the fans, in order to better serve their unique needs and desires. Fan culture studies, as an outgrowth of media studies, examine the nature and make up of fan communities. This article posits a cross disciplinary approach using fan studies to inform tourism research. This article reports on an analysis of attendees to an event celebrating of the 20th anniversary of the filming of the popular American film “The Shawshank Redemption.” Attendee characteristics, desired outcomes, and motivating factors were examined.

  15. Contextualizing Corruption: A Cross-Disciplinary Approach to Studying Corruption in Organizations

    Directory of Open Access Journals (Sweden)

    Kanti Pertiwi

    2018-04-01

    Full Text Available This paper aims to establish how organization and management research, an extensive field that has contributed a great deal to research on corruption, could apply insights from other disciplines in order to advance the understanding of corruption, often considered as a form of unethical behavior in organizations. It offers an analysis of important contributions of corruption research, taking a ‘rationalist perspective’, and highlights the central tensions and debates within this vast body of literatures. It then shows how these debates can be addressed by applying insights from corruption studies, adopting anthropological lens. The paper thus proposes a cross-disciplinary approach, which focuses on studying corruption by looking at what it means to individuals implicated by the phenomenon while engaging in social relations and situated in different contexts. It also offers an alternative approach to the study of corruption amidst claims that anti-corruption efforts have failed to achieve desirable results.

  16. [Exploration of nursing art and aesthetic experiences: cross-disciplinary links and dialogues].

    Science.gov (United States)

    Sheu, Shuh-Jen

    2013-08-01

    Interdisciplinary understanding is crucial for readers today. This article integrates the ideas of four care-aesthetics-column writers in order to illustrate and discuss nursing art and aesthetic care experiences in a cross-disciplinary conversation. This article reflects critically on the art, culture, and nature of nursing in the five themes of: 1) the shape of nursing knowledge, "science" or "art"?; 2) the caring arts: passively regulative or consciously creative labor?; 3) busy hospital workers: a landscape of persons and objects or the creators of the scenery?; 4) nursing skills, arts, and the Tao; and 5) art liberation: is the nursing profession in need of a revolution or fundamental reform? This article utilizes diverse and occasionally contradictory points of view together with practical examples in order to encourage readers to interlink their disparate professional nursing skills and draw aesthetic knowledge from multiple sources and experiences.

  17. A redox proteomics approach to investigate the mode of action of nanomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Riebeling, Christian [German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin (Germany); Wiemann, Martin [IBE R& D gGmbH, Institute for Lung Health, Münster (Germany); Schnekenburger, Jürgen [Biomedical Technology Center, Westfälische Wilhelms-University, Münster (Germany); Kuhlbusch, Thomas A.J. [Institute of Energy and Environmental Technology (IUTA) e.V., Air Quality & Sustainable Nanotechnology, Duisburg (Germany); Center for Nanointegration CENIDE, University of Duisburg-Essen, Duisburg, Germany, (Germany); Wohlleben, Wendel [BASF SE, Material Physics, Ludwigshafen (Germany); Luch, Andreas [German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin (Germany); Haase, Andrea, E-mail: andrea.haase@bfr.bund.de [German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin (Germany)

    2016-05-15

    Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye based read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways. - Highlights: • Oxidative stress is a general paradigm for nanomaterial hazard mechanism of action. • Reactive oxygen species generation can be predicted using acellular assays. • Cellular assays based on fluorescence suffer from interference by nanomaterials. • Protein carbonylation is an irreversible and predictive mark of oxidative stress.

  18. Accelerating early anti-tuberculosis drug discovery by creating mycobacterial indicator strains that predict mode of action

    KAUST Repository

    Boot, Maikel

    2018-04-13

    Due to the rise of drug resistant forms of tuberculosis there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on stricto sensu life-death screening that give little qualitative information. In doing so, promising compound scaffolds or non-optimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early TB drug discovery, we performed RNA sequencing on Mycobacterium tuberculosis and Mycobacterium marinum to map the stress responses that follow upon exposure to sub-inhibitory concentrations of antibiotics with known targets: ciprofloxacin, ethambutol, isoniazid, streptomycin and rifampicin. The resulting dataset comprises the first overview of transcriptional stress responses of mycobacteria to different antibiotics. We show that antibiotics can be distinguished based on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in M. marinum. We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct stress reporters. In total, three functional reporters were constructed to respond to DNA damage, cell wall damage and ribosomal inhibition. Subsequently, these reporter strains were used to screen a small anti-TB compound library to predict the mode of action. In doing so, we could identify the putative mode of action for three novel compounds, which confirms our approach.

  19. A tripartite mode of action approach for investigating the impact of aneugens on tubulin polymerization.

    Science.gov (United States)

    Stock, Valerie; Sutter, Andreas; Raschke, Marian; Queisser, Nina

    2018-04-01

    Chemical-induced disruption of the cellular microtubule network is one key mechanism of aneugenicity. Since recent data indicate that genotoxic effects of aneugens show nonlinear dose-response relationships, margins of safety can be derived with the ultimate goal to perform a risk assessment for the support of drug development. Furthermore, microtubule-interacting compounds are widely used for cancer treatment. While there is a need to support the risk assessment of tubulin-interacting chemicals using reliable mechanistic assays, no standard assays exist to date in regulatory genotoxicity testing for the distinction of aneugenic mechanisms. Recently reported methods exclusively rely on either biochemical, morphological, or cytometric endpoints. Since data requirements for the diverse fields of application of those assays differ strongly, the use of multiple assays for a correct classification of aneugens is ideal. We here report a tripartite mode of action approach comprising a cell-free biochemical polymerization assay and the cell-based methods cellular imaging and flow cytometry. The biochemical assay measures tubulin polymerization over time whereas the two cell-based assays quantify tubulin polymer mass. We herein show that the flow cytometric method yielded IC 50 values for tubulin destabilizers and EC 50 values for tubulin stabilizers as well as cell cycle information. In contrast, cellular imaging complemented these findings with characteristic morphological patterns. Biochemical analysis yielded kinetic information on tubulin polymerization. This multiplex approach is able to create holistic effect profiles which can be individually customized to the research question with regard to quality, quantity, usability, and economy. Environ. Mol. Mutagen. 59:188-201, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. 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.

  1. 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…

  2. A framing approach to cross-disciplinary research collaboration: experiences from a large-scale research project on adaptive water management

    NARCIS (Netherlands)

    Dewulf, A.; Francois, G.; Pahl-Wostl, C.; Taillieu, T.

    2007-01-01

    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

  3. Space Geodesy: The Cross-Disciplinary Earth science (Vening Meinesz Medal Lecture)

    Science.gov (United States)

    Shum, C. K.

    2012-04-01

    Geodesy during the onset of the 21st Century is evolving into a transformative cross-disciplinary Earth science field. The pioneers before or after the discipline Geodesy was defined include Galileo, Descartes, Kepler, Newton, Euler, Bernoulli, Kant, Laplace, Airy, Kelvin, Jeffreys, Chandler, Meinesz, Kaula, and others. The complicated dynamic processes of the Earth system manifested by interactions between the solid Earth and its fluid layers, including ocean, atmosphere, cryosphere and hydrosphere, and their feedbacks are linked with scientific problems such as global sea-level rise resulting from natural and anthropogenic climate change. Advances in the precision and stability of geodetic and fundamental instrumentations, including clocks, satellite or quasar tracking sensors, altimetry and lidars, synthetic aperture radar interferometry (InSAR), InSAR altimetry, gravimetry and gradiometry, have enabled accentuate and transformative progress in cross-disciplinary Earth sciences. In particular, advances in the measurement of the gravity with modern free-fall methods have reached accuracies of 10-9 g (~1 μGal or 10 nm/s2) or better, allowing accurate measurements of height changes at ~3 mm relative to the Earth's center of mass, and mass transports within the Earth interior or its geophysical fluids, enabling global quantifications of climate-change signals. These contemporary space geodetic and in situ sensors include, but not limited to, satellite radar and laser altimetry/lidars, GNSS/SLR/VLBI/DORIS, InSAR, spaceborne gravimetry from GRACE (Gravity Recovery And Climate Experiment twin-satellite mission) and gradiometry from GOCE (Global Ocean Circulation Experiment), tide gauges, and hydrographic data (XBT/MBT/Argo). The 2007 Intergovernmental Panel for Climate Change (IPCC) study, the Fourth Assessment Report (AR4), substantially narrowed the discrepancy between observation and the known geophysical causes of sea-level rise, but significant uncertainties

  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. Cross-disciplinary Participatory & Contextual Design Research: Creating a Teacher Dashboard Application

    Directory of Open Access Journals (Sweden)

    Troy D. Abel

    2014-02-01

    Full Text Available Concepts of Human Computer Interaction have crossed disciplinary boundaries allowing the discovery of underlying stakeholder affordances to emerge during the design research phase of system design. For the current scenario, middle school mathematics teachers as data-driven decision makers are inundated with diagnostic and assessment data, resulting in data deluge. The situation is unlikely to subside as digital technologies and media are broadly adopted for instruction and learning. Teachers could benefit from tools to quickly sift through this data to inform classroom instruction. Data should be visualized in a way that teachers can make real-time formative and summative assessments of student progress. The purpose of this article is to introduce a mixed-method mode of discovery to uncover affordances innate to classroom teachers during the design of an iPad data visualization application. These technology-assisted “dashboard” platforms could serve as efficient and effective interventions to deal with the copious amounts of data streams now available to teachers.

  6. 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.

  7. Designing Research Services: Cross-Disciplinary Administration and the Research Lifecycle

    Science.gov (United States)

    Madden, G.

    2017-12-01

    The sheer number of technical and administrative offices involved in the research lifecycle, and the lack of shared governance and shared processes across those offices, creates challenges to the successful preservation of research outputs. Universities need a more integrated approach to the research lifecycle that allows us to: recognize a research project as it is being initiated; identify the data associated with the research project; document and track any compliance, security, access, and publication requirements associated with the research and its data; follow the research and its associated components across the research lifecycle; and finally recognize that the research has come to a close so we can trigger the various preservation, access, and communications processes that close the loop, inform the public, and promote the continued progress of science. Such an approach will require cooperation, communications, and shared workflow tools that tie together (often across many years) PIs, research design methodologists, grants offices, contract negotiators, central research administrators, research compliance specialists, desktop IT support units, server administrators, high performance computing facilities, data centers, specialized data transfer networks, institutional research repositories, institutional data repositories, and research communications groups, all of which play a significant role in the technical or administrative success of research. This session will focus on progress towards improving cross-disciplinary administrative and technical cooperation at Penn State University, with an emphasis on generalizable approaches that can be adopted elsewhere.

  8. 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.

  9. “Weak direct” and “Strong indirect” interactions are the mode of action of food factors

    Directory of Open Access Journals (Sweden)

    Tetsuya Konishi

    2014-06-01

    Full Text Available Age-dependent and lifestyle related diseases such as metabolic syndromes have become a social problem worldwide. Since these disorders are closely related to dietary lifestyle, the old saying “foods are medicine” is now being re-evaluated. Thus, dietary protection against these diseases is attracting much attention. As research into functional foods advances, a book of knowledge is being accumulated on the active ingredients, termed “food factors”, present in food resources. Identifying such molecules usually follows the conventional methodology used for finding drug candidates from natural resources. The question has arisen as to whether the mode of action of food factors as molecules is the same as that of drugs. In this article, the functional properties of food factors and drugs are comparatively reviewed and the characteristic features of food factor function is discussed, based on the idea of “weak direct” and “strong indirect” actions of food factors to their receptors

  10. Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures

    International Nuclear Information System (INIS)

    Proctor, Deborah M.; Suh, Mina; Campleman, Sharan L.; Thompson, Chad M.

    2014-01-01

    Highlights: • No published or well recognized MOA for Cr(VI)-induced lung tumors exists. • MOA analysis for Cr(VI)-induced lung cancer was conducted to inform risk assessment. • Cr(VI) epidemiologic, toxicokinetic, toxicological, mechanistic data were evaluated. • Weight of evidence does not support a mutagenic MOA for Cr(VI)-induced lung cancer. • Non-linear approaches should be considered for evaluating Cr(VI) lung cancer risk. - Abstract: Inhalation of hexavalent chromium [Cr(VI)] is associated with increased lung cancer risk among workers in several industries, most notably chromate production workers exposed to high concentrations of Cr(VI) (≥100 μg/m 3 ), for which clear exposure–response relationships and respiratory irritation and tissue damage have been reported. Data from this industry are used to assess lung cancer risk associated with environmental and current occupational exposures, occurring at concentrations that are significantly lower. There is considerable uncertainty in the low dose extrapolation of historical occupational epidemiology data to assess risk at current exposures because no published or well recognized mode of action (MOA) for Cr(VI)-induced lung tumors exists. We conducted a MOA analysis for Cr(VI)-induced lung cancer evaluating toxicokinetic and toxicological data in humans and rodents and mechanistic data to assess plausibility, dose–response, and temporal concordance for potential MOAs. Toxicokinetic data support that extracellular reduction of Cr(VI), which limits intracellular absorption of Cr(VI) and Cr(VI)-induced toxicity, can be overwhelmed at high exposure levels. In vivo genotoxicity and mutagenicity data are mostly negative and do not support a mutagenic MOA. Further, both chronic bioassays and the epidemiologic literature support that lung cancer occurs at exposures that cause tissue damage. Based on this MOA analysis, the overall weight of evidence supports a MOA involving deposition and accumulation

  11. Mode of action of pectin lyase A of Aspergillus niger on differently C(6)-substituted oligogalacturonides.

    Science.gov (United States)

    van Alebeek, Gert-Jan W M; Christensen, Tove M I E; Schols, Henk A; Mikkelsen, Jørn D; Voragen, Alphons G J

    2002-07-19

    A thorough investigation of the mode of action of Aspergillus niger (4M-147) pectin lyase A (PLA) on differently C(6)-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 ester (ethyl esterification) or transamidation resulted in (almost) complete loss of conversion. The PLA activity increased with increasing length of the substrate up to a degree of polymerization (DP) of 8 indicating the presence of at least eight subsites on the enzyme. Product analysis demonstrated the formation of several Delta 4,5 unsaturated products and their saturated counterparts. The Delta 4,5 unsaturated trimer was the main product up to DP 8. For DP 9 and 10 Delta 4,5 unsaturated tetramer was the major product. Based upon the bond cleavage frequencies, a provisional subsite map was calculated, which supports the presence of eight subsites. By limited alkaline de-esterification of fully methyl-esterified pentamer and hexamer two sets of partially methyl-esterified pentamers (x and y methyl groups) and hexamers (a and b methyl groups) were prepared. Matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS) analysis demonstrated that the methyl-ester distribution was fully random. Using these partially methyl-esterified oligogalacturonides as substrates for PLA a 10-fold decrease in reaction rate was recorded compared with the fully methyl-esterified counterparts. Analysis of the methyl-ester distribution of the products showed that PLA tolerates carboxyl groups in the substrate binding cleft. At either subsite +2, +4, or -1 to -4 a free carboxyl group could be tolerated, whereas methyl-esters were obligatory at subsite +1 and +3. So PLA is capable to cleave the bond between a methyl-esterified and a non-esterified galacturonic acid residue, where the newly formed Delta 4,5 unsaturated non-reducing end residue always contains a

  12. Raman spectroscopy, electronic microscopy and SPME-GC-MS to elucidate the mode of action of a new antimicrobial food packaging material.

    Science.gov (United States)

    Clemente, Isabel; Aznar, Margarita; Salafranca, Jesús; Nerín, Cristina

    2017-02-01

    One critical challenge when developing a new antimicrobial packaging material is to demonstrate the mode of action of the antimicrobials incorporated into the packaging. For this task, several analytical techniques as well as microbiology are required. In this work, the antimicrobial properties of benzyl isothiocyanate, allyl isothiocyanate and essential oils of cinnamon and oregano against several moulds and bacteria have been evaluated. Benzyl isothiocyanate showed the highest antimicrobial activity and it was selected for developing the new active packaging material. Scanning electron microscopy and Raman spectroscopy were successfully used to demonstrate the mode of action of benzyl isothiocyanate on Escherichia coli. Bacteria exhibited external modifications such as oval shape and the presence of septum surface, but they did not show any disruption or membrane damage. To provide data on the in vitro action of benzyl isothiocyanate and the presence of inhibition halos, the transfer mechanism to the cells was assessed using solid-phase microextraction-gas chromatography-mass spectrometry. Based on the transfer system, action mechanism and its stronger antimicrobial activity, benzyl isothiocyanate was incorporated to two kinds of antimicrobial labels. The labels were stable and active for 140 days against two mould producers of ochratoxin A; Penicillium verrucosum is more sensitive than Aspergillus ochraceus. Details about the analytical techniques and the results obtained are shown and discussed. Graphical Abstract Antimicrobial evaluation of pure compounds, incorporation in the packaging and study for mode of action on S. coli by Raman, SEM and SPME-GC-MS.

  13. 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

    2011-06-01

    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 distinct disciplines [chemistry (CHEM) and exercise physiology (EPHE)] combined to study exercise thermoregulation and sweat analysis. Twenty-eight senior BSc Kinesiology (EPHE) students and 42 senior BSc CHEM students participated as part of their mutually exclusive, respective courses. The effectiveness of this laboratory environment was evaluated qualitatively using written comments collected from all students as well as from formal focus groups conducted after the CD laboratory with a representative cohort from each class (n = 16 CHEM students and 9 EPHE students). An open coding strategy was used to analyze the data from written feedback and focus group transcripts. Coding topics were generated and used to develop five themes found to be consistent for both groups of students. These themes reflected the common student perceptions that the CD experience was valuable and that students enjoyed being able to apply academic concepts to practical situations as well as the opportunity to interact with students from another discipline of study. However, students also reported some challenges throughout this experience that stemmed from the combination of laboratory groups from different disciplines with limited modification to the design of the original, pre-CD, learning environments. The results indicate that this laboratory created an effective learning opportunity that fostered student interest and enthusiasm for learning. The findings also provide information that could inform subsequent design and implementation of similar CD experiences to enhance engagement of all students and improve instructor efficacy.

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

    KAUST Repository

    Zhang, Yi-Fan; Kitano, Yoshikazu; Nogata, Yasuyuki; Zhang, Yu; Qian, Pei-Yuan

    2012-01-01

    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

  15. Elucidating Duramycin’s Bacterial Selectivity and Mode of Action on the Bacterial Cell Envelope

    Directory of Open Access Journals (Sweden)

    Sahar Hasim

    2018-02-01

    Full Text Available The use of naturally occurring antimicrobial peptides provides a promising route to selectively target pathogenic agents and to shape microbiome structure. Lantibiotics, such as duramycin, are one class of bacterially produced peptidic natural products that can selectively inhibit the growth of other bacteria. However, despite longstanding characterization efforts, the microbial selectivity and mode of action of duramycin are still obscure. We describe here a suite of biological, chemical, and physical characterizations that shed new light on the selective and mechanistic aspects of duramycin activity. Bacterial screening assays have been performed using duramycin and Populus-derived bacterial isolates to determine species selectivity. Lipidomic profiles of selected resistant and sensitive strains show that the sensitivity of Gram-positive bacteria depends on the presence of phosphatidylethanolamine (PE in the cell membrane. Further the surface and interface morphology were studied by high resolution atomic force microscopy and showed a progression of cellular changes in the cell envelope after treatment with duramycin for the susceptible bacterial strains. Together, these molecular and cellular level analyses provide insight into duramycin’s mode of action and a better understanding of its selectivity.

  16. 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.

  17. Anti-dengue virus serotype 2 activity and mode of action of a novel peptide.

    Science.gov (United States)

    Chew, M-F; Tham, H-W; Rajik, M; Sharifah, S H

    2015-10-01

    To identify a novel antiviral peptide against dengue virus serotype 2 (DENV-2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. A phage display peptide library was biopanned against purified DENV-2 and resulted in the identification and selection of a peptide (peptide gg-ww) for further investigation. ELISA was performed, and peptide gg-ww was shown to possess the highest binding affinity against DENV-2. Thus, peptide gg-ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real-time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg-ww on DENV-2 infection in Vero cells. Three different assays (pre-, simultaneous and post-treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg-ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l(-1) . Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. Peptide gg-ww displayed antiviral action against DENV-2 by targeting an early stage of viral replication (i.e. during viral entry). Peptide gg-ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug. © 2015 The Society for Applied Microbiology.

  18. 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.

  19. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents.

    Science.gov (United States)

    Almeida, Joana R; Freitas, Micaela; Cruz, Susana; Leão, Pedro N; Vasconcelos, Vitor; Cunha, Isabel

    2015-07-24

    Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. 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 was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species.

  20. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents

    Directory of Open Access Journals (Sweden)

    Joana R. Almeida

    2015-07-01

    Full Text Available Effective and ecofriendly antifouling (AF compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement screening tests. 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 was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species.

  1. 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.

  2. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Délia Szok

    2015-07-01

    Full Text Available Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.

  3. 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.

  4. 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.

  5. Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

    Science.gov (United States)

    Zhou, Wei; Zeng, Cheng; Liu, RenHua; Chen, Jie; Li, Ru; Wang, XinYan; Bai, WenWen; Liu, XiaoYuan; Xiang, TingTing; Zhang, Lin; Wan, YongJi

    2016-05-01

    Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

  6. 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.

  7. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......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...

  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...... 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...

  9. Development and implementation of the IPCS conceptual framework for evaluating mode of action of chemical carcinogens

    International Nuclear Information System (INIS)

    Dybing, E.

    2002-01-01

    The framework developed by the International Programme on Chemical Safety (IPCS) for assessing the mode of action of tumour induction of chemicals in experimental animals has been illustrated with d-limonene, sodium saccharin, di(2-ethylhexyl)phthalate (DEHP) and sulfamethazine as examples. d-Limonene causes renal tumours only in male rats through a response associated with α 2u -globulin. Sodium saccharin induces urinary bladder tumours only in male rats through formation of a urinary precipitate causing erosion of the bladder surface and extensive regenerative hyperplasia. DEHP causes liver tumours in rats and mice through activation of the receptor PPARα leading to peroxisome proliferation and hepatocellular proliferation. Sulfamethazine induces thyroid follicular cell tumours in rats and mice through a mechanism involving altered thyroid hormone homeostasis

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

    Science.gov (United States)

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

    2014-03-01

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

  11. EEG alpha activity reflects motor preparation rather than the mode of action selection

    Directory of Open Access Journals (Sweden)

    Marie-Pierre eDeiber

    2012-08-01

    Full Text Available Alpha-band activity (8-13 Hz is suppressed by sensory stimulation and movements, modulated by attention, working memory and mental tasks and may be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None, a posterior alpha power decrease (event-related desynchronization, ERD dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha power increase (event-related synchronization, ERS, suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: 1 a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and 2 an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation. 

  12. 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.

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

    International Nuclear Information System (INIS)

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena

    2014-01-01

    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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Transcriptional profile of diuron-induced toxicity on the urinary bladder of male Wistar rats to inform mode of action.

    Science.gov (United States)

    Ihlaseh, Shadia M; Bailey, Kathryn A; Hester, Susan D; Jones, Carlton; Ren, Hongzu; Cardoso, Ana Paula F; Oliveira, Maria Luiza C S; Wolf, Douglas C; de Camargo, João Lauro V

    2011-08-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that induces rat urinary bladder urothelial tumors at high dietary levels (2500 ppm). The specific mode of action and molecular alterations triggered by diuron, however, have not been clarified. The present study evaluated the dose-dependent effects of mucosal alterations and transcriptional changes in the urinary bladder of rats exposed to diuron. Six-week-old male Wistar rats were treated with 0, 60, 125, 1250, and 2500 ppm of diuron in the diet for 20 weeks. Histologic examination showed urothelial hyperplasia present in rats treated with either 1250 or 2500 ppm of diuron but not 60 or 125 ppm. Comprehensive gene expression analyses of urothelial cell RNA were conducted using Affymetrix microarrays. The numbers of differentially expressed transcripts between each treatment group and control increased with diuron dose. Based on similar histology and gene expression responses, the treatment groups were regrouped into a high-dose (1250 and 2500 ppm) and low-dose group (60 and 125 ppm). These data suggest that persistent exposure to high dietary concentrations of diuron induces oxidative stress, increases cellular metabolism, and enhances cell death that is associated with sustained urothelial hyperplasia.

  19. Evaluation of the efficacy and mode of action of biological control for suppression of ganoderma boninense in oil palm

    International Nuclear Information System (INIS)

    Alexander, A.; Abdullah, S.; Rossall, S.; Chong, K.P.

    2017-01-01

    The ability of potential antagonists, a commercial product containing combinations of microorganisms (TR1) to control Ganoderma boninense growth was investigated in this research. TR1 contained multiple strains of Bacillus spp. and Trichoderma spp. The results from field experiments showed that TR1 was all able to reduce the colonization of G. boninense, based on re-isolation of the pathogen onto a selective medium and the reduction of ergosterol content compared to untreated controls. Effectiveness of TR1 was therefore further investigated for mode of action studies. Scanning Electron Microscopy (SEM) observations of Ganoderma mycelium, recovered from bioassay plates on which TR1 had inhibited fungal growth, showed that the mycelium was highly disrupted and lysed after exposure to the treatment. The production of potentially antifungal components produced by TR1 microbes in broth cultures was further investigated using Liquid Chromatography Mass Spectrometry (LCMS). Several antimicrobial compounds, which could inhibit G. boninense were detected, including pyrene-1,6-dione, 12-deoxyaklanonic acid, N-methyl-a-aminoisobutyric acid, 4-O-8',5"-5'-dehydrotriferulic acid, halstoctacosanolide A, N-acetyl-leu-leu-tyr-amide, 12-oxo-10Z-dodecenoic acid, Gly-Met-OH and lovastatin. These metabolites probably contribute to the antagonistic effect against G. boninense. The use of TR1 could offer an alternative to the use of fungicides and is worthy of further investigation for the control of Ganoderma infection of oil palm. (author)

  20. Efficacy and mode of action of an immunomodulator herbal preparation containing Echinacea, wild indigo, and white cedar.

    Science.gov (United States)

    Wüstenberg, P; Henneicke-von Zepelin, H H; Köhler, G; Stammwitz, U

    1999-01-01

    Using the example of an allopathic herbal combined preparation containing Echinacea root, wild indigo root, and white cedar leaf tips (Echinaceae radix + Baptisiae tinctoriae radix + Thujae occidentalis herba = Esberitox N), the efficacy and mode of action of a phytoimmunomodulator, or immune system enhancer, is described. Efficacy of the immunomodulator has been demonstrated in studies of acute viral respiratory tract infections and infections requiring antibiotic therapy. In a recent study compliant to GCP, the therapeutic superiority of the herbal immunomodulator over placebo was confirmed as statistically significant and clinically relevant. The present overview describes a model of the antigen-independent mode of action of phytoimmunomodulation ("immunobalancing").

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

    Energy Technology Data Exchange (ETDEWEB)

    Jager, Tjalling [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)]. E-mail: tjalling@bio.vu.nl; Crommentuijn, Trudie [Ministry of Spatial Planning, Housing and the Environment (VROM), Rijnstraat 8, P.O. Box 30945, 2500 GX, The Hague (Netherlands); Gestel, Cornelis A.M. van [Department of Animal Ecology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands); Kooijman, Sebastiaan A.L.M. [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)

    2007-01-15

    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. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms.

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

    International Nuclear Information System (INIS)

    Jager, Tjalling; Crommentuijn, Trudie; Gestel, Cornelis A.M. van; 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. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms

  3. Mode of action of alginic acid compound in the reduction of gastroesophageal reflux

    International Nuclear Information System (INIS)

    Malmud, L.S.; Charkes, N.D.; Littlefield, J.; Reilley, J.; Stern, H.; Rosenberg, R.; Fisher, R.S.

    1979-01-01

    This study was designed to evaluate quantitatively the mode of action of alginic acid compound (AAC) in the treatment of patients with symptomatic gastroesophageal reflux. Gastroesophageal scintigraphy using an orally administered Tc-99m sulfur colloid solution was used to demonstrate that AAC decreased significantly the gastroesophageal reflux index from (9.9 +- 1.3)% to (6.5 +- 0.8)% (p < 0.05). No alteration of lower esophageal sphincter pressure was observed. After AAC was suitably labeled with Sr-87m, a dual-nuclide scintigraphic technique was used to show that most (< 75%) of the AAC was located in the upper half of the stomach in both normal subjects and patients with gastroesophageal reflux. In those subjects in whom reflux did occur after treatment with AAC, the Sr-87m-AAC refluxed into the esophagus preferentially compared with the liquid containing Tc-99m sulfur colloid. These findings suggest that AAC diminishes gastroesophageal reflux by means of its foaming, floating, and viscous properties

  4. 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.

  5. 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.

  6. Broflanilide: A meta-diamide insecticide with a novel mode of action.

    Science.gov (United States)

    Nakao, Toshifumi; Banba, Shinichi

    2016-02-01

    Broflanilide is a meta-diamide [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamide] that exhibits high larvicidal activity against Spodoptera litura. It has been suggested that broflanilide is metabolized to desmethyl-broflanilide and that it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl-broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil. It has been proposed that the site of action for desmethyl-broflanilide is close to G336 in the M3 region of the Drosophila RDL GABA receptor. However, although the site of action for desmethyl-broflanilide appears to overlap with that of macrocyclic lactones, different modes of actions have been demonstrated for desmethyl-broflanilide and the macrocyclic lactones. The mechanisms underlying the high selectivity of meta-diamides are also discussed in this review. Broflanilide is expected to become a prominent insecticide because it is effective against pests with resistance to cyclodienes and fipronil. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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

  8. Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine.

    Science.gov (United States)

    Yu, Xiuling; Wei, Peng; Wang, Ziwen; Liu, Yuxiu; Wang, Lizhong; Wang, Qingmin

    2016-02-01

    The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity. Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine. The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents. © 2015 Society of Chemical Industry.

  9. Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach

    International Nuclear Information System (INIS)

    Sarrabay, A.; Hilmi, C.; Tinwell, H.; Schorsch, F.; Pallardy, M.; Bars, R.; Rouquié, D.

    2015-01-01

    ABSTRACT: The dose–response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose–response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10 mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LH increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (< 0.1 mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10 mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1 mg/kg/day, as well as an increase in testosterone blood level at 10 mg/kg/day. Each key event dose–response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose–response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. - Highlights: • Dose–response characterization of endocrine mediated toxicity is an on-going debate. • A wide range of dose levels of flutamide was evaluated on young adult male rats. • Flutamide induces threshold effects using on standard and molecular tools.

  10. Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach

    Energy Technology Data Exchange (ETDEWEB)

    Sarrabay, A. [INSERM, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry (France); UniverSud, INSERM, UMR-996 “Inflammation, Chemokines and Immunopathology”, Châtenay-Malabry (France); Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon (France); Hilmi, C.; Tinwell, H.; Schorsch, F. [Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon (France); Pallardy, M. [INSERM, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry (France); UniverSud, INSERM, UMR-996 “Inflammation, Chemokines and Immunopathology”, Châtenay-Malabry (France); Bars, R. [Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon (France); Rouquié, D., E-mail: david.rouquie@bayer.com [Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon (France)

    2015-12-15

    ABSTRACT: The dose–response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose–response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10 mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LH increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (< 0.1 mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10 mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1 mg/kg/day, as well as an increase in testosterone blood level at 10 mg/kg/day. Each key event dose–response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose–response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. - Highlights: • Dose–response characterization of endocrine mediated toxicity is an on-going debate. • A wide range of dose levels of flutamide was evaluated on young adult male rats. • Flutamide induces threshold effects using on standard and molecular tools.

  11. A mode-of-action approach for the identification of genotoxic carcinogens.

    Directory of Open Access Journals (Sweden)

    Lya G Hernández

    Full Text Available Distinguishing between clastogens and aneugens is vital in cancer risk assessment because the default assumption is that clastogens and aneugens have linear and non-linear dose-response curves, respectively. Any observed non-linearity must be supported by mode of action (MOA analyses where biological mechanisms are linked with dose-response evaluations. For aneugens, the MOA has been well characterised as disruptors of mitotic machinery where chromosome loss via micronuclei (MN formation is an accepted endpoint used in risk assessment. In this study we performed the cytokinesis-block micronucleus assay and immunofluorescence mitotic machinery visualisation in human lymphoblastoid (AHH-1 and Chinese Hamster fibroblast (V79 cell lines after treatment with the aneugen 17-β-oestradiol (E₂. Results were compared to previously published data on bisphenol-A (BPA and Rotenone data. Two concentration-response approaches (the threshold-[Td] and benchmark-dose [BMD] approaches were applied to derive a point of departure (POD for in vitro MN induction. BMDs were also derived from the most sensitive carcinogenic endpoint. Ranking comparisons of the PODs from the in vitro MN and the carcinogenicity studies demonstrated a link between these two endpoints for BPA, E₂ and Rotenone. This analysis was extended to include 5 additional aneugens, 5 clastogens and 3 mutagens and further concentration and dose-response correlations were observed between PODs from the in vitro MN and carcinogenicity. This approach is promising and may be further extended to other genotoxic carcinogens, where MOA and quantitative information from the in vitro MN studies could be used in a quantitative manner to further inform cancer risk assessment.

  12. Mode of action of Cr(VI) in immunocytes of earthworms: Implications for animal health.

    Science.gov (United States)

    Sforzini, Susanna; Moore, Michael N; Mou, Zhuofan; Boeri, Marta; Banni, Mohamed; Viarengo, Aldo

    2017-04-01

    Chromium (Cr) is one of the major and most detrimental pollutant, widely present in the environment as a result of several anthropogenic activities. In mammalian cells, Cr(VI) is known to enhance reactive oxygen species (ROS) production and to cause toxic and genotoxic effects. Less commonly investigated are the effects and mode of action of this contaminant in invertebrates, particularly in soil organisms. In this work, earthworms of the species Eisenia andrei were exposed for 1 and 3 days to various sublethal concentrations of Cr(VI) (2, 15, 30µgmL -1 ) using the paper contact toxicity test. In amoeboid leukocytes we investigated intracellular ROS and lipoperoxide production, oxidative DNA damage, and the effects on different cell functions. The analysis of the results shows that Cr(VI) triggered severe adverse reactions; the first events were an increase of intracellular ROS levels, generating in the cells oxidative stress conditions leading to membrane lipid peroxidation and oxidative DNA damage. Lysosomes showed relevant changes such as a strong membrane destabilization, which was accompanied by an increased catabolism of cytoplasmic proteins and accumulation of lipofuscin. With an increase in the dose and/or time of exposure, the physiological status of intracellular organelles (such as lysosomes, nucleus and mitochondria) showed further impairment and amoebocyte immune functions were adversely affected, as shown by the decrease of the phagocytic activity. By mapping the responses of the different parameters evaluated, diagnostic of (oxidative) stress events, against lysosomal membrane stability, a "health status" indicator (able to describe the stress syndrome from its early phase to pathology), we have shown that this biomarker is suitable as a prognostic test for health of earthworms. This is viewed as a crucial step toward the derivation of explanatory frameworks for prediction of pollutant impact on animal health. Copyright © 2017. Published by

  13. 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

  14. Modes of Action, Resistance and Toxicity of Insecticides Targeting Nicotinic Acetylcholine Receptors.

    Science.gov (United States)

    Ihara, Makoto; Buckingham, Steven D; Matsuda, Kazuhiko; Sattelle, David B

    2017-01-01

    Nicotinic acetylcholine receptors (nAChRs) of insects play a key role in fast excitatory neurotransmission. Several classes of insecticides target insect nAChRs, which are composed of subunit members of a family of multiple subunit encoding genes. Alternative splicing and RNA A-to-I editing can add further to receptor diversity. Native and recombinant receptors have been explored as sites of insecticide action using radioligands, electrophysiology and site-directed mutagenesis. We have reviewed the properties of native and recombinant insect nAChRs, the challenges of functional recombinant insect nAChR expression, nAChR interactions with ligands acting at orthosteric and allosteric sites and in particular their interactions with insecticides. Actions on insect nAChRs of cartap, neonicotinoids, spinosyns, sulfoxamines, butenolides and mesoionic insecticides are reviewed and current knowledge of their modes of action are addressed. Mutations that add to our understanding of insecticide action and those leading to resistance are discussed. Co-crystallisation of neonicotinoids with the acetylcholine binding protein (AChBP), a surrogate for the nAChR ligand binding domain, has proved instructive. Toxicity issues relating to insecticides targeting nAChRs are also considered. An overview of insecticide classes targeting insect nAChRs has enhanced our understanding of these important receptors and their insecticide binding sites. However, the subunit composition of native nAChRs remains poorly understood and functional expression still presents difficulties. These topics together with improved understanding of the precise sites of insecticide actions on insect nAChRs will be the subject of future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. 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.

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

    International Nuclear Information System (INIS)

    LeBaron, Matthew J.; Geter, David R.; Rasoulpour, Reza J.; Gollapudi, B. Bhaskar; Thomas, Johnson; Murray, Jennifer; Kan, H. Lynn; Wood, Amanda J.; Elcombe, Cliff; Vardy, Audrey; McEwan, Jillian; Terry, Claire; Billington, Richard

    2013-01-01

    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

  17. 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

  18. 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

    2014-01-01

    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. The potential value of the mode of action (MOA)/human relevance (species concordance) framework in considering relative weight of evidence (WOE) amongst different cases and hypothesized MOA(s) is explored based on the content of several published assessments

  19. 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

    ligands in the ChEMBL database. Two compounds were confirmed as agonist and inverse agonist, respectively, in both IP accumulation and Ca2+ mobilization assays. The screening setup presented in this work is computationally inexpensive and therefore particularly useful in an academic setting as it enables-simultaneous...

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Fiona Williamson

    2016-11-01

    Full Text Available Abstract 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

  2. 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

  3. Evaluation of genotoxic effects of surface waters using a battery of bioassays indicating different mode of action.

    Science.gov (United States)

    Han, Yingnan; Li, Na; Oda, Yoshimitsu; Ma, Mei; Rao, Kaifeng; Wang, Zijian; Jin, Wei; Hong, Gang; Li, Zhiguo; Luo, Yi

    2016-11-01

    With the burgeoning contamination of surface waters threatening human health, the genotoxic effects of surface waters have received much attention. Because mutagenic and carcinogenic compounds in water cause tumors by different mechanisms, a battery of bioassays that each indicate a different mode of action (MOA) is required to evaluate the genotoxic effects of contaminants in water samples. In this study, 15 water samples from two source water reservoirs and surrounding rivers in Shijiazhuang city of China were evaluated for genotoxic effects. Target chemical analyses of 14 genotoxic pollutants were performed according to the Environmental quality standards for surface water of China. Then, the in vitro cytokinesis-block micronucleus (CBMN) assay, based on a high-content screening technique, was used to detect the effect of chromosome damage. The SOS/umu test using strain TA1535/pSK1002 was used to detect effects on SOS repair of gene expression. Additionally, two other strains, NM2009 and NM3009, which are highly sensitive to aromatic amines and nitroarenes, respectively, were used in the SOS/umu test to avoid false negative results. In the water samples, only two of the genotoxic chemicals listed in the water standards were detected in a few samples, with concentrations that were below water quality standards. However, positive results for the CBMN assay were observed in two river samples, and positive results for the induction of umuC gene expression in TA1535/pSK1002 were observed in seven river samples. Moreover, positive results were observed for NM2009 with S9 and NM3009 without S9 in some samples that had negative results using the strain TA1535/pSK1002. Based on the results with NM2009 and NM3009, some unknown or undetected aromatic amines and nitroarenes were likely in the source water reservoirs and the surrounding rivers. Furthermore, these compounds were most likely the causative pollutants for the genotoxic effect of these water samples. Therefore

  4. 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.

  5. 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

  6. Proteomics analysis suggests broad functional changes in potato leaves triggered by phosphites and a complex indirect mode of action against Phytophthora infestans.

    Science.gov (United States)

    Lim, Sanghyun; Borza, Tudor; Peters, Rick D; Coffin, Robert H; Al-Mughrabi, Khalil I; Pinto, Devanand M; Wang-Pruski, Gefu

    2013-11-20

    Phosphite (salts of phosphorous acid; Phi)-based fungicides are increasingly used in controlling oomycete pathogens, such as the late blight agent Phytophthora infestans. In plants, low amounts of Phi induce pathogen resistance through an indirect mode of action. We used iTRAQ-based quantitative proteomics to investigate the effects of phosphite on potato plants before and after infection with P. infestans. Ninety-three (62 up-regulated and 31 down-regulated) differentially regulated proteins, from a total of 1172 reproducibly identified proteins, were identified in the leaf proteome of Phi-treated potato plants. Four days post-inoculation with P. infestans, 16 of the 31 down-regulated proteins remained down-regulated and 42 of the 62 up-regulated proteins remained up-regulated, including 90% of the defense proteins. This group includes pathogenesis-related, stress-responsive, and detoxification-related proteins. Callose deposition and ultrastructural analyses of leaf tissues after infection were used to complement the proteomics approach. This study represents the first comprehensive proteomics analysis of the indirect mode of action of Phi, demonstrating broad effects on plant defense and plant metabolism. The proteomics data and the microscopy study suggest that Phi triggers a hypersensitive response that is responsible for induced resistance of potato leaves against P. infestans. Phosphie triggers complex functional changes in potato leaves that are responsible for the induced resistance against Phytophthora infestans. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Variations in Textualization: A Cross-generic and Cross-disciplinary Study, Implications for Readability of the Academic Discourse

    Directory of Open Access Journals (Sweden)

    Mina Abbasi Bonabi

    2018-01-01

    Full Text Available According to discoursal views on language, variations in textualization strategies are always socio-contextually motivated and never happen at random. The textual forms employed in a text, along with many other discoursal and contextual factors, could certainly affect the readability of the text, making it more or less processable for the same reader. On the basis of these assumptions, the present study set out to examine how our data varied across genres and disciplines in terms of our target textual forms. These forms are as follows: the magnitude of T-unit (MOTU, the degree of embeddedness of the main verb in T-unit (DE, the physical distance between the verb and its satellite elements (PD, the magnitude of the noun phrase appearing before the verb (MOX, and the magnitude of noun phrase appearing after the verb (MOY. Our data consisted of 20 research articles randomly selected from two different disciplines of Biology and Applied Linguistics, to be analyzed in terms of the above-named textual strategies. One way ANOVA and post hoc Tukey tests were used for data analyses. The results revealed cross-generic as well as cross-disciplinary differences in the employment of the above textual forms. These findings were discussed in terms of the academic concepts and discourse on the one hand and the possible effect of the required textual forms on the readability of the text on the other hand.

  8. Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae RS-1.

    Science.gov (United States)

    Yang, Chunlan; Li, Bin; Ge, Mengyu; Zhou, Kaile; Wang, Yanli; Luo, Ju; Ibrahim, Muhammad; Xie, Guanlin; Sun, Guochang

    2014-06-04

    Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) strain RS-1 was examined in this study. Result from this study indicated that chitosan solutions at 0.10, 0.20, and 0.40mg/mL inhibited the in vitro growth of Aaa strain RS-1, and in general the inhibitory efficiency increased with the increase of both chitosan concentration and the incubation time. Antibacterial activity of chitosan in this study may be mainly due to the damage of cell membrane, which was evidenced by both the cell lysis observed by transmission electron microscopy, and the increased release of cell materials based on the measurement of cell membrane integrity. Furthermore, chitosan solutions at concentrations of 0.1, 0.2, and 0.4mg/mL markedly inhibited bacterial biofilm formation compared to the control, and the inhibitory effect increased with the increase of chitosan concentration. In addition, quantitative real-time PCR of the 10 secretion system related genes revealed the differential expression of genes in particular ompA/motB, emphasizing the importance of this gene in the response of Aaa strain RS-1 to chitosan stress. These results indicated that the antibacterial mode of action of chitosan may be mainly due to membrane disruption and lysis, reduction of biofilm formation, and gene expression change. Overall, the results clearly indicated that chitosan had the potential to control bacterial brown stripe of rice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Capitalizing on Cultural difference: A Cross-Disciplinary Outlook from Social Psychology to International Business

    OpenAIRE

    Katiuscia Vaccarini; Barbara Pojaghi

    2015-01-01

    Drawing upon social psychology and international business literature the aim of this paper is to raise international managers and entrepreneurs’ awareness on the opportunity to capitalize on cultural differences and diversity in international business settings. Following our quantitative and qualitative data collection based on managers’ perceptions on cultural differences, we propose and illustrate the sociocognitive value of a group cultural laboratory as a potential “structured business pr...

  10. The Proteomics Stock Market Project. A Cross-Disciplinary Collaboration in Biochemistry and Business Education

    Science.gov (United States)

    Keller, Heath; Cox, James R.

    2004-04-01

    Students taking courses in different disciplines can work together to add unique elements to their educational experience. A model for this type of pedagogical approach has been established in the Proteomics Stock Market Project, a collaborative effort between instructors and students in the Department of Chemistry and Department of Management, Marketing, and Business Administration at Murray State University. Stage I involved biochemistry students investigating the topic of proteomics and choosing companies for potential investment based only on scientific investigation. Marketing and management students completed Stage II and provided an investment analysis on the companies selected in Stage I. In Stage III, the biochemistry students focused on a particular company and investigated a protein-based therapeutic product. Blackboard software was utilized in each stage of the project to facilitate the exchange of information and electronic documents. This project was designed to give biochemistry students an appreciation for the emerging field of proteomics and the marketing and management students a flavor for real-world applications of business principles. During the project, students were exposed to ideas and concepts not typically covered in their courses. With this involvement, the students had the opportunity to gain a broader perspective of course content compared to a more traditional curriculum.

  11. 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

  12. Modals in the construction of research articles: A cross-disciplinary perspective

    Directory of Open Access Journals (Sweden)

    Matthew Peacock

    2014-03-01

    Full Text Available This paper describes a corpus-based analysis of variation in the distribution and function of modals and their role in the expression of “stance” in a corpus of 600 research articles (RAs across twelve disciplines. Stance is an expression of attitudes, judgments, or assessments towards the truth of propositions (Biber et al., 1999, and part of the important function of claiming and confirming membership of discourse communities and therefore in constructing identity. Three functional categories of modals perform a valuable role in the construction of stance: Possibility/Ability, Obligation/Necessity, and Prediction (Biber et al., 1999. However, very little research seems to have investigated variation across disciplines or their use in the RA. The corpus was analysed using WordSmith Tools (Scott, 2004, followed by manual checking of the function of every occurrence. Inter- and intra-rater agreement was also checked. Many statistically significant disciplinary differences were found, along with numerous marked differences with individual modals. Further examination of the corpus revealed considerable disciplinary variation in the patterns and verbs associated with the target modals, and a number of sub-functions of the topics covered by the modals. Conclusions are that modals perform an important role in the construction of stance.

  13. Enabling cross-disciplinary research by linking data to Open Access publications

    Science.gov (United States)

    Rettberg, N.

    2012-04-01

    OpenAIREplus focuses on the linking of research data to associated publications. The interlinking of research objects has implications for optimising the research process, allowing the sharing, enrichment and reuse of data, and ultimately serving to make open data an essential part of first class research. The growing call for more concrete data management and sharing plans, apparent at funder and national level, is complemented by the increasing support for a scientific infrastructure that supports the seamless access to a range of research materials. This paper will describe the recently launched OpenAIREplus and will detail how it plans to achieve its goals of developing an Open Access participatory infrastructure for scientific information. OpenAIREplus extends the current collaborative OpenAIRE project, which provides European researchers with a service network for the deposit of peer-reviewed FP7 grant-funded Open Access publications. This new project will focus on opening up the infrastructure to data sources from subject-specific communities to provide metadata about research data and publications, facilitating the linking between these objects. The ability to link within a publication out to a citable database, or other research data material, is fairly innovative and this project will enable users to search, browse, view, and create relationships between different information objects. In this regard, OpenAIREplus will build on prototypes of so-called "Enhanced Publications", originally conceived in the DRIVER-II project. OpenAIREplus recognizes the importance of representing the context of publications and datasets, thus linking to resources about the authors, their affiliation, location, project data and funding. The project will explore how links between text-based publications and research data are managed in different scientific fields. This complements a previous study in OpenAIRE on current disciplinary practices and future needs for infrastructural

  14. {cross-disciplinary} Data CyberInfrastructure: A Different Approach to Developing Collaborative Earth and Environmental Science Research Platforms

    Science.gov (United States)

    Lenhardt, W. C.; Krishnamurthy, A.; Blanton, B.; Conway, M.; Coposky, J.; Castillo, C.; Idaszak, R.

    2017-12-01

    An integrated science cyberinfrastructure platform is fast becoming a norm in science, particularly where access to distributed resources, access to compute, data management tools, and collaboration tools are accessible to the end-user scientist without the need to spin up these services on their own. There platforms have various types of labels ranging from data commons to science-as-a-service. They tend to share common features, as outlined above. What tends to distinguish these platforms, however, is their affinity for particular domains, NanoHub - nanomaterials, iPlant - plant biology, Hydroshare - hydrology, and so on. The challenge still remains how to enable these platforms to be more easily adopted for use by other domains. This paper will provide an overview of RENCI's approach to creating a science platform that can be more easily adopted by new communities while also endeavoring to accelerate their research. At RENCI, we started with Hydroshare, but have now worked to generalize the methodology for application to other domains. This new effort is called xDCi, or {cross-disciplinary} Data CyberInfrastructure. We have adopted a broader approach to the challenge of domain adoption and includes two key elements in addition to the technology component. The first of these is how development is operationalized. RENCI implements a DevOps model of continuous development and deployment. This greatly increases the speed by which a new platform can come online and be refined to meet domain needs. DevOps also allows for migration over time, i.e. sustainability. The second element is a concierge model. In addition to the technical elements, and the more responsive development process, RENCI also supports domain adoption of the platform by providing a concierge service— dedicated expertise- in the following areas, Information Technology, Sustainable Software, Data Science, and Sustainability. The success of the RENCI methodology is illustrated by the adoption of the

  15. 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.

  16. 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.

  17. 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

  18. 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 et al. 2001, Irianto and Austin, 2002, Hong et al. 2005). Many 12 of these mechanisms only apply to probiotics added to feed, but the latter three are relevant to 13 water borne additives such as B. cereus. 14 15 The bioremediation capability... its attractiveness as a probiotic 10 and biological agent for aquaculture. The siderophore producing capability of the B. cereus 11 isolate addresses the severe shortage of probiotics able to facilitate competitive exclusion based 12 on iron...

  19. 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.

  20. The Cyclic Antibacterial Peptide Enterocin AS-48: Isolation, Mode of Action, and Possible Food Applications

    Directory of Open Access Journals (Sweden)

    María José Grande Burgos

    2014-12-01

    Full Text Available Enterocin AS-48 is a circular bacteriocin produced by Enterococcus. It contains a 70 amino acid-residue chain circularized by a head-to-tail peptide bond. The conformation of enterocin AS-48 is arranged into five alpha-helices with a compact globular structure. Enterocin AS-48 has a wide inhibitory spectrum on Gram-positive bacteria. Sensitivity of Gram-negative bacteria increases in combination with outer-membrane permeabilizing treatments. Eukaryotic cells are bacteriocin-resistant. This cationic peptide inserts into bacterial membranes and causes membrane permeabilization, leading ultimately to cell death. Microarray analysis revealed sets of up-regulated and down-regulated genes in Bacillus cereus cells treated with sublethal bacteriocin concentration. Enterocin AS-48 can be purified in two steps or prepared as lyophilized powder from cultures in whey-based substrates. The potential applications of enterocin AS-48 as a food biopreservative have been corroborated against foodborne pathogens and/or toxigenic bacteria (Listeria monocytogenes, Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella enterica and spoilage bacteria (Alicyclobacillus acidoterrestris, Bacillus spp., Paenibacillus spp., Geobacillus stearothermophilus, Brochothrix thermosphacta, Staphylococcus carnosus, Lactobacillus sakei and other spoilage lactic acid bacteria. The efficacy of enterocin AS-48 in food systems increases greatly in combination with chemical preservatives, essential oils, phenolic compounds, and physico-chemical treatments such as sublethal heat, high-intensity pulsed-electric fields or high hydrostatic pressure.

  1. The Cyclic Antibacterial Peptide Enterocin AS-48: Isolation, Mode of Action, and Possible Food Applications.

    Science.gov (United States)

    Grande Burgos, María José; Pulido, Rubén Pérez; Del Carmen López Aguayo, María; Gálvez, Antonio; Lucas, Rosario

    2014-12-08

    Enterocin AS-48 is a circular bacteriocin produced by Enterococcus. It contains a 70 amino acid-residue chain circularized by a head-to-tail peptide bond. The conformation of enterocin AS-48 is arranged into five alpha-helices with a compact globular structure. Enterocin AS-48 has a wide inhibitory spectrum on Gram-positive bacteria. Sensitivity of Gram-negative bacteria increases in combination with outer-membrane permeabilizing treatments. Eukaryotic cells are bacteriocin-resistant. This cationic peptide inserts into bacterial membranes and causes membrane permeabilization, leading ultimately to cell death. Microarray analysis revealed sets of up-regulated and down-regulated genes in Bacillus cereus cells treated with sublethal bacteriocin concentration. Enterocin AS-48 can be purified in two steps or prepared as lyophilized powder from cultures in whey-based substrates. The potential applications of enterocin AS-48 as a food biopreservative have been corroborated against foodborne pathogens and/or toxigenic bacteria (Listeria monocytogenes, Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella enterica) and spoilage bacteria (Alicyclobacillus acidoterrestris, Bacillus spp., Paenibacillus spp., Geobacillus stearothermophilus, Brochothrix thermosphacta, Staphylococcus carnosus, Lactobacillus sakei and other spoilage lactic acid bacteria). The efficacy of enterocin AS-48 in food systems increases greatly in combination with chemical preservatives, essential oils, phenolic compounds, and physico-chemical treatments such as sublethal heat, high-intensity pulsed-electric fields or high hydrostatic pressure.

  2. 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.

  3. Mode of action of sodium arsenate on laboratory colonies of the pharaoh's ant Monomorium pharaonis L

    Energy Technology Data Exchange (ETDEWEB)

    Berndt, K P

    1974-01-01

    Arsenate compounds for pest control have been displayed on large scale by modern insecticides. In the control of the pharaoh's ant the arsenates however still remain an important means for eradication. The present study points out, that the mortality of workers and queens, respectively, are not the decisive factors of action as assumed until now. The causes for the extinction of the ant colonies after application of sodium arsenate are based on a combination of larval mortality and the induction of sterility in the queens, the sterility being the most important factor. A number of other factors moreover are working advantageously. First, the poison bait is not repellent and is well accepted by the workers, and is either stored in the nest or distributed trophalactically. Whereas with the workers there occurs a strongly delayed mortality, the larvae are being inhibited in their development after a few hours, shortly before pupation, or they are being paralyzed, whereby the further pupation would by cut off. The younger larvae normally do not come to pupation, but are being stunted and would be eliminated from the nest. The reproducing females, being the last members in the social chain, are protected in the polygynous society from the lethal action of the poison, although otherwise susceptible in the same way as workers. After a certain time sub-lethal doses of sodium arsenate lead to a decrease in fecundity. Egg production is suppressed dependent on the duration of the poison application up to permanent sterility. On the basis of these investigations some suggestions for practical control of the pharaoh's ant have been derived.

  4. The toxicological mode of action and the safety of synthetic amorphous silica—A nanostructured material

    International Nuclear Information System (INIS)

    Fruijtier-Pölloth, Claudia

    2012-01-01

    Synthetic amorphous silica (SAS), in the form of pyrogenic (fumed), precipitated, gel or colloidal SAS, has been used in a wide variety of industrial and consumer applications including food, cosmetics and pharmaceutical products for many decades. Based on extensive physico-chemical, ecotoxicology, toxicology, safety and epidemiology data, no environmental or health risks have been associated with these materials if produced and used under current hygiene standards and use recommendations. With internal structures in the nanoscale size range, pyrogenic, precipitated and gel SAS are typical examples of nanostructured materials as recently defined by the International Organisation for Standardisation (ISO). The manufacturing process of these SAS materials leads to aggregates of strongly (covalently) bonded or fused primary particles. Weak interaction forces (van der Waals interactions, hydrogen bonding, physical adhesion) between aggregates lead to the formation of micrometre (μm)-sized agglomerates. Typically, isolated nanoparticles do not occur. In contrast, colloidal SAS dispersions may contain isolated primary particles in the nano-size range which can be considered nano-objects. The size of the primary particle resulted in the materials often being considered as “nanosilica” and in the inclusion of SAS in research programmes on nanomaterials. The biological activity of SAS can be related to the particle shape and surface characteristics interfacing with the biological milieu rather than to particle size. SAS adsorbs to cellular surfaces and can affect membrane structures and integrity. Toxicity is linked to mechanisms of interactions with outer and inner cell membranes, signalling responses, and vesicle trafficking pathways. Interaction with membranes may induce the release of endosomal substances, reactive oxygen species, cytokines and chemokines and thus induce inflammatory responses. None of the SAS forms, including colloidal nano-sized particles, were

  5. The toxicological mode of action and the safety of synthetic amorphous silica-a nanostructured material.

    Science.gov (United States)

    Fruijtier-Pölloth, Claudia

    2012-04-11

    Synthetic amorphous silica (SAS), in the form of pyrogenic (fumed), precipitated, gel or colloidal SAS, has been used in a wide variety of industrial and consumer applications including food, cosmetics and pharmaceutical products for many decades. Based on extensive physico-chemical, ecotoxicology, toxicology, safety and epidemiology data, no environmental or health risks have been associated with these materials if produced and used under current hygiene standards and use recommendations. With internal structures in the nanoscale size range, pyrogenic, precipitated and gel SAS are typical examples of nanostructured materials as recently defined by the International Organisation for Standardisation (ISO). The manufacturing process of these SAS materials leads to aggregates of strongly (covalently) bonded or fused primary particles. Weak interaction forces (van der Waals interactions, hydrogen bonding, physical adhesion) between aggregates lead to the formation of micrometre (μm)-sized agglomerates. Typically, isolated nanoparticles do not occur. In contrast, colloidal SAS dispersions may contain isolated primary particles in the nano-size range which can be considered nano-objects. The size of the primary particle resulted in the materials often being considered as "nanosilica" and in the inclusion of SAS in research programmes on nanomaterials. The biological activity of SAS can be related to the particle shape and surface characteristics interfacing with the biological milieu rather than to particle size. SAS adsorbs to cellular surfaces and can affect membrane structures and integrity. Toxicity is linked to mechanisms of interactions with outer and inner cell membranes, signalling responses, and vesicle trafficking pathways. Interaction with membranes may induce the release of endosomal substances, reactive oxygen species, cytokines and chemokines and thus induce inflammatory responses. None of the SAS forms, including colloidal nano-sized particles, were shown

  6. 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

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

    Science.gov (United States)

    Rashid, M. H.; Hossain, M. Ashraf; Kashem, M. A.; Kumar, Shiv; Rafii, M. Y.; Latif, M. A.

    2014-01-01

    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. PMID:24723819

  8. 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.

  9. Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Florie Desriac

    2018-04-01

    Full Text Available We have previously shown that the C-type Natriuretic Peptide (CNP, a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

  10. 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.

  11. Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action

    International Nuclear Information System (INIS)

    Colman, Joan; Rice, Glenn E.; Wright, J. Michael; Hunter, E. Sidney; Teuschler, Linda K.; Lipscomb, John C.; Hertzberg, Richard C.; Simmons, Jane Ellen; Fransen, Margaret; Osier, Mark; Narotsky, Michael G.

    2011-01-01

    Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.

  12. Antibacterial Activities and Possible Modes of Action of Acacia nilotica (L. Del. against Multidrug-Resistant Escherichia coli and Salmonella

    Directory of Open Access Journals (Sweden)

    Muhammad Bilal Sadiq

    2017-01-01

    Full Text Available Medicinal plants are frequently used for the treatment of various infectious diseases. The objective of this study was to evaluate the antibacterial activity and mode of action of Acacia nilotica and the antibiogram patterns of foodborne and clinical strains of Escherichia coli and Salmonella. The mechanism of action of acacia extracts against E. coli and Salmonella was elucidated by observing morphological damages including cell integrity and cell membrane permeability, as well as changes in cell structures and growth patterns in kill-time experiments. The clinical isolates of E. coli and Salmonella were found resistant to more of the tested antibiotics, compared to food isolates. Minimum inhibitory concentration and minimum bactericidal concentration of acacia leaf extracts were in the ranges of 1.56–3.12 mg/mL and 3.12–6.25 mg/mL, respectively, whereas pods and bark extracts showed somewhat higher values of 3.12–6.25 mg/mL and 6.25–12.5 mg/mL, respectively, against all tested pathogens. The release of electrolytes and essential cellular constituents (proteins and nucleic acids indicated that acacia extracts damaged the cellular membrane of the pathogens. These changes corresponded to simultaneous reduction in the growth of viable bacteria. This study indicates that A. nilotica can be a potential source of new antimicrobials, effective against antibiotic-resistant strains of pathogens.

  13. 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.

  14. Antifungal modes of action of Saccharomyces and other biocontrol yeasts against fungi isolated from sour and grey rots.

    Science.gov (United States)

    Nally, M C; Pesce, V M; Maturano, Y P; Rodriguez Assaf, L A; Toro, M E; Castellanos de Figueroa, L I; Vazquez, F

    2015-07-02

    The aim of this study was to determine the putative modes of action of 59 viticultural yeasts (31 Saccharomyces and 28 non-Saccharomyces) that inhibited fungi isolated from sour and grey rot in grapes. Inhibition of fungal mycelial growth by metabolites, enzyme activities (laminarinases, chitinases), antifungal volatiles, competition for nutrients (siderophores, Niche Overlap Index (NOI)), inhibition of fungal spore germination and decreased germinal tube length and induction of resistance were assayed. Biofungicide yeasts were classified into "antifungal patterns", according to their mechanisms of action. Thirty isolates presented at least two of the mechanisms assayed. We propose that inhibition of fungal mycelial growth by metabolites, laminarinases, competition for nutrients, inhibition of fungal spore germination and decreased germinal tube length, and antifungal volatiles by Saccharomyces and non-Saccharomyces viticultural yeasts is used as putative biocontrol mechanisms against phytopathogenic fungi. Twenty-four different antifungal patterns were identified. Siderophore production (N)and a combination of siderophore production and NOI>0.92 (M)were the most frequent antifungal patterns observed in the biofungicide yeasts assayed. Elucidation of these mechanisms could be useful for optimization of an inoculum formulation, resulting in a more consistent control of grey and sour rot with Saccharomyces and non-Saccharomyces biocontrol yeasts. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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.

  16. Purification, Characterization, and Mode of Action of Plantaricin GZ1-27, a Novel Bacteriocin against Bacillus cereus.

    Science.gov (United States)

    Du, Hechao; Yang, Jie; Lu, Xiaohong; Lu, Zhaoxin; Bie, Xiaomei; Zhao, Haizhen; Zhang, Chong; Lu, Fengxia

    2018-05-09

    Bacillus cereus is an opportunistic pathogen that causes foodborne diseases. We isolated a novel bacteriocin, designated plantaricin GZ1-27, and elucidated its mode of action against B. cereus. Plantaricin GZ1-27 was purified using ammonium sulfate precipitation, gel-filtration chromatography, and RP-HPLC. MALDI-TOF/MS revealed that its molecular mass was 975 Da, and Q-TOF-MS/MS analysis predicted the amino acid sequence as VSGPAGPPGTH. Plantaricin GZ1-27 showed thermostability and pH stability. The antibacterial mechanism was investigated using flow cytometry, confocal laser-scanning microscopy, scanning and transmission electron microscopy, and RT-PCR, which revealed that GZ1-27 increased cell membrane permeability, triggered K + leakage and pore formation, damaged cell membrane integrity, altered cell morphology and intracellular organization, and reduced the expression of genes related to cytotoxin production, peptidoglycan synthesis, and cell division. These results suggest that plantaricin GZ1-27 effectively inhibits B. cereus at both the cellular and the molecular levels and is a potential natural food preservative targeting B. cereus.

  17. 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.

  18. 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.

  19. Mode of action and dose-response framework analysis for receptor-mediated toxicity : The aryl hydrocarbon receptor as a case study

    NARCIS (Netherlands)

    Budinsky, R. A.; Schrenk, D.; Simon, T.; Van Den Berg, M.; Reichard, J. F.; Silkworth, J. B.; Aylward, L. L.; Brix, A.; Gasiewicz, T.; Kaminski, N.; Perdew, G.; Starr, T. B.; Walker, N. J.; Rowlands, J. C.

    2014-01-01

    Dioxins and dioxin-like compounds are tumor promoters that cause liver cancer in rats and mice. The aryl hydrocarbon receptor (AHR) has been implicated as a key component in this tumor promotion response. Despite extensive knowledge of the toxicology of dioxins, no mode of action (MOA) hypothesis

  20. 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...

  1. DOSE RESPONSE FROM HIGH THROUGHPUT GENE EXPRESSION STUDIES AND THE INFLUENCE OF TIME AND CELL LINE ON INFERRED MODE OF ACTION BY ONTOLOGIC ENRICHMENT (SOT)

    Science.gov (United States)

    Gene expression with ontologic enrichment and connectivity mapping tools is widely used to infer modes of action (MOA) for therapeutic drugs. Despite progress in high-throughput (HT) genomic systems, strategies suitable to identify industrial chemical MOA are needed. The L1000 is...

  2. DIFFICULTY OF MODE OF ACTION DETERMINATION FOR TRICHLOROETHYLENE: AN EXAMPLE OF COMPLEX INTERACTIONS OF METABOLITES AND OTHER CHEMICAL EXPOSURES (Journal Article)

    Science.gov (United States)

    The mode(s) of action (MOA) of a pollutant for adverse health effects may be dependent on the mixture of metabolites resulting from exposure to a single agent and may also be affected by co-exposure to pollutants that have similar targets or affected pathways. Trichloroethylene ...

  3. 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

    formation inhibition). Four modes of action (were also found to be associated with high ACRs: (1) lysyl oxidase inhibition leading to notochord distortion, (2) putative methemoglobin formation or haemolytic anemia, (3) endocrine disruption, and (4) compounds with neuromuscular toxicity. It was discussed...

  4. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

  5. 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.

  6. Cytotoxicity and regenerative proliferation as the mode of action for diuron-induced urothelial carcinogenesis in the rat.

    Science.gov (United States)

    da Rocha, Mitscheli S; Nascimento, Merielen G; Cardoso, Ana Paula F; de Lima, Patrícia L A; Zelandi, Edneia A; de Camargo, João Lauro V; de Oliveira, Maria Luiza C S

    2010-01-01

    Diuron, a substituted urea herbicide, is carcinogenic to the urinary bladder of rats at high dietary levels. Its proposed carcinogenic mode of action (MOA) includes urothelial cytotoxicity and necrosis followed by regenerative cell proliferation and sustained urothelial hyperplasia. Cytotoxicity could be induced either by urinary solids or by chemical toxicity by diuron and/or metabolites excreted in the urine. Diuron was not genotoxic in a previous single-cell gel (comet) assay, but possible cross-linking activity remained to be evaluated. The present study explored the MOA of diuron and the effect of urinary acidification on the development of urothelial lesions. Male Wistar rats were fed diuron (2500 ppm, about 130 mg/kg of body weight) either with or without NH(4)Cl 10,000 ppm to acidify the urine. Reversibility of urothelial changes was also examined. The animals were euthanized after 15, 25, or 30 weeks. Diuron-fed rats had urinary amorphous precipitate and magnesium ammonium phosphate crystals similar to control animals. Groups treated with diuron + NH(4)Cl showed decreased urinary pH and reduced amounts of urinary crystals and precipitate. Urothelial necrosis and simple hyperplasia were observed by light microscopy and scanning electron microscopy both in diuron- and in diuron + NH(4)Cl-treated groups. Cytotoxicity and proliferative changes were mostly reversible. A modified comet assay developed in vitro with Chinese hamster ovary cells showed that diuron did not induce DNA cross-links. These data suggest that cytotoxicity with consequent regenerative cell proliferation is the predominant MOA for diuron rat urothelial carcinogenesis, the cytotoxicity being chemically induced and not due to urinary solids.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

    2015-06-11

    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.

  12. 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.

  13. 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.

  14. Resistance mutation conserved between insects and mites unravels the benzoylurea insecticide mode of action on chitin biosynthesis.

    Science.gov (United States)

    Douris, Vassilis; Steinbach, Denise; Panteleri, Rafaela; Livadaras, Ioannis; Pickett, John Anthony; Van Leeuwen, Thomas; Nauen, Ralf; Vontas, John

    2016-12-20

    Despite the major role of chitin biosynthesis inhibitors such as benzoylureas (BPUs) in the control of pests in agricultural and public health for almost four decades, their molecular mode of action (MoA) has in most cases remained elusive. BPUs interfere with chitin biosynthesis and were thought to interact with sulfonylurea receptors that mediate chitin vesicle transport. Here, we uncover a mutation (I1042M) in the chitin synthase 1 (CHS1) gene of BPU-resistant Plutella xylostella at the same position as the I1017F mutation reported in spider mites that confers etoxazole resistance. Using a genome-editing CRISPR/Cas9 approach coupled with homology-directed repair (HDR) in Drosophila melanogaster, we introduced both substitutions (I1056M/F) in the corresponding fly CHS1 gene (kkv). Homozygous lines bearing either of these mutations were highly resistant to etoxazole and all tested BPUs, as well as buprofezin-an important hemipteran chitin biosynthesis inhibitor. This provides compelling evidence that BPUs, etoxazole, and buprofezin share in fact the same molecular MoA and directly interact with CHS. This finding has immediate effects on resistance management strategies of major agricultural pests but also on mosquito vectors of serious human diseases such as Dengue and Zika, as diflubenzuron, the standard BPU, is one of the few effective larvicides in use. The study elaborates on how genome editing can directly, rapidly, and convincingly elucidate the MoA of bioactive molecules, especially when target sites are complex and hard to reconstitute in vitro.

  15. 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.

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

    International Nuclear Information System (INIS)

    Dhanjal, Jaspreet Kaur; Goyal, Sukriti; Sharma, Sudhanshu; Hamid, Rabia; Grover, Abhinav

    2014-01-01

    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

  17. Assessment of possible carcinogenicity of oxyfluorfen to humans using mode of action analysis of rodent liver effects.

    Science.gov (United States)

    Stagg, Nicola J; LeBaron, Matthew J; Eisenbrandt, David L; Gollapudi, B Bhaskar; Klaunig, James E

    2012-08-01

    Oxyfluorfen is a herbicide that is not genotoxic and produces liver toxicity in rodents, following repeated administration at high dose levels. Lifetime rodent feeding studies reported in 1977 with low-purity oxyfluorfen (85%) showed no increase in any tumor type in rats (800 ppm, high dose) and only a marginally increased incidence of hepatocellular tumors in male CD-1 mice at the highest dose (200 ppm). To evaluate the potential carcinogenicity of the currently registered oxyfluorfen (> 98% purity), we conducted a series of short-term liver mode of action (MOA) toxicology studies in male CD-1 mice administered dietary doses of 0, 40, 200, 800, and 1600 ppm for durations of 3, 7, 10, or 28 days. MOA endpoints examined included liver weight, histopathology, cell proliferation, nuclear receptor-mediated gene expression, and other peroxisome proliferator-specific endpoints and their reversibility. Minimal liver effects were observed in mice administered doses at or below 200 ppm for up to 28 days. Increased liver weight, single-cell necrosis, cell proliferation, and peroxisomal acyl-CoA oxidase (ACO) were observed at 800 ppm after 28 days, but there was no increase in peroxisomes. Expression of Cyp2b10 and Cyp4a10 transcripts, markers of constitutive androstane receptor and peroxisome proliferator activated receptor α nuclear receptor activation, respectively, were increased at 800 and 1600 ppm after 3 or 10 days. Collectively, these data along with the negative genotoxicity demonstrate that oxyfluorfen (> 98% purity) has the potential to induce mouse liver tumors through a nongenotoxic, mitogenic MOA with a clear threshold and is not predicted to be carcinogenic in humans at relevant exposure levels.

  18. Comparative mode of action of novel hybrid peptide CS-1a and its rearranged amphipathic analogue CS-2a.

    Science.gov (United States)

    Joshi, Seema; Bisht, Gopal S; Rawat, Diwan S; Maiti, Souvik; Pasha, Santosh

    2012-10-01

    Cell selective, naturally occurring, host defence cationic peptides present a good template for the design of novel peptides with the aim of achieving a short length with improved antimicrobial potency and selectivity. A novel, short peptide CS-1a (14 residues) was derived using a sequence hybridization approach on sarcotoxin I (39 residues) and cecropin B (35 residues). The sequence of CS-1a was rearranged to enhance amphipathicity with the help of a Schiffer-Edmundson diagram to obtain CS-2a. Both peptides showed good antibacterial activity in the concentration range 4-16 μg·mL(-1) against susceptible as well as drug-resistant bacterial strains, including the clinically relevant pathogens Acenatobacter sp. and methicillin-resistant Staphylococcus aureus. The major thrust of these peptides is their nonhaemolytic activity against human red blood cells up to a high concentration of 512 μg·mL(-1). Compared to CS-1a, amphipathic peptide CS-2a showed a more pronounced α-helical conformation, along with a better membrane insertion depth in bacterial mimic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) small unilamellar vesicles. With equivalent lipid-binding affinity, the two peptides assumed different pathways of membrane disruption, as demonstrated by calcein leakage and the results of transmission electron microscopy on model bacterial mimic large unilamellar vesicles. Extending the work from model membranes to intact Escherichia coli cells, differences in membrane perturbation were visible in microscopic images of peptide-treated E. coli. The present study describes two novel short peptides with potent activity, cell selectivity and divergent modes of action that will aid in the future design of peptides with better therapeutic potential. © 2012 The Authors Journal compilation © 2012 FEBS.

  19. 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.

  20. 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.

  1. Mode of action analysis for the synthetic pyrethroid metofluthrin-induced rat liver tumors: evidence for hepatic CYP2B induction and hepatocyte proliferation.

    Science.gov (United States)

    Deguchi, Yoshihito; Yamada, Tomoya; Hirose, Yukihiro; Nagahori, Hirohisa; Kushida, Masahiko; Sumida, Kayo; Sukata, Tokuo; Tomigahara, Yoshitaka; Nishioka, Kazuhiko; Uwagawa, Satoshi; Kawamura, Satoshi; Okuno, Yasuyoshi

    2009-03-01

    Two-year treatment with high doses of Metofluthrin produced hepatocellular tumors in both sexes of Wistar rats. To understand the mode of action (MOA) by which the tumors are produced, a series of studies examined the effects of Metofluthrin on hepatic microsomal cytochrome P450 (CYP) content, hepatocellular proliferation, hepatic gap junctional intercellular communication (GJIC), oxidative stress and apoptosis was conducted after one or two weeks of treatment. The global gene expression profile indicated that most genes with upregulated expression with Metofluthrin were metabolic enzymes that were also upregulated with phenobarbital. Metofluthrin induced CYP2B and increased liver weights associated with centrilobular hepatocyte hypertrophy (increased smooth endoplasmic reticulum [SER]), and induction of increased hepatocellular DNA replication. CYP2B1 mRNA induction by Metofluthrin was not observed in CAR knockdown rat hepatocytes using the RNA interference technique, demonstrating that Metofluthrin induces CYP2B1 through CAR activation. Metofluthrin also suppressed hepatic GJIC and induced oxidative stress and increased antioxidant enzymes, but showed no alteration in apoptosis. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. All of these effects were reversible upon cessation of treatment. Metofluthrin did not cause cytotoxicity or peroxisome proliferation. Thus, it is highly likely that the MOA for Metofluthrin-induced liver tumors in rats is through CYP induction and increased hepatocyte proliferation, similar to that seen for phenobarbital. Based on analysis with the International Life Sciences Institute/Risk Science Institute MOA framework, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans, at least at expected levels of exposure.

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

    International Nuclear Information System (INIS)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger; Stein, Jürgen; Fürst, Robert; Steinhilber, Dieter; Ulrich-Rückert, Sandra

    2015-01-01

    (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 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 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 PDEs, SIRT1

  3. Effect and mode of action of the Texel muscling QTL (TM-QTL) on carcass traits in purebred Texel lambs.

    Science.gov (United States)

    Macfarlane, J M; Lambe, N R; Matika, O; Johnson, P L; Wolf, B T; Haresign, W; Bishop, S C; Bünger, L

    2014-07-01

    different mode of action of the two main effects of TM-QTL (on growth and muscling).

  4. 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

  5. Sensitivity of species to chemicals: dose-response characteristics for various test types (LC(50), LR(50) and LD(50)) and modes of action.

    Science.gov (United States)

    Hendriks, A Jan; Awkerman, Jill A; de Zwart, Dick; Huijbregts, Mark A J

    2013-11-01

    While variable sensitivity of model species to common toxicants has been addressed in previous studies, a systematic analysis of inter-species variability for different test types, modes of action and species is as of yet lacking. Hence, the aim of the present study was to identify similarities and differences in contaminant levels affecting cold-blooded and warm-blooded species administered via different routes. To that end, data on lethal water concentrations LC50, tissue residues LR50 and oral doses LD50 were collected from databases, each representing the largest of its kind. LC50 data were multiplied by a bioconcentration factor (BCF) to convert them to internal concentrations that allow for comparison among species. For each endpoint data set, we calculated the mean and standard deviation of species' lethal level per compound. Next, the means and standard deviations were averaged by mode of action. Both the means and standard deviations calculated depended on the number of species tested, which is at odds with quality standard setting procedures. Means calculated from (BCF) LC50, LR50 and LD50 were largely similar, suggesting that different administration routes roughly yield similar internal levels. Levels for compounds interfering biochemically with elementary life processes were about one order of magnitude below that of narcotics disturbing membranes, and neurotoxic pesticides and dioxins induced death in even lower amounts. Standard deviations for LD50 data were similar across modes of action, while variability of LC50 values was lower for narcotics than for substances with a specific mode of action. The study indicates several directions to go for efficient use of available data in risk assessment and reduction of species testing. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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

  8. 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

  9. 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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 30 or an ED 50 –ED 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

  10. 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.

  11. 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

  12. 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 (

  13. Partial purification and characterization of the mode of action of enterocin S37: a bacteriocin produced by Enterococcus faecalis S37 isolated from poultry feces.

    Science.gov (United States)

    Belguesmia, Y; Choiset, Y; Prévost, H; Dalgalarrondo, M; Chobert, J-M; Drider, D

    2010-01-01

    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 80(o)C 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, alpha-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 K(ATP) channels. This study contributed to gain more insights into the mode of action of enterocins.

  14. 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.

  15. 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.

    Science.gov (United States)

    Gafni, Aviva; Calderon, Claudia E; Harris, Raviv; Buxdorf, Kobi; Dafa-Berger, Avis; Zeilinger-Reichert, Einat; Levy, Maggie

    2015-01-01

    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 as 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.

  16. 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.

  17. 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.

  18. 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.

  19. Characterizing the structure-function relationship reveals the mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula.

    Science.gov (United States)

    Tseng, Tien-Sheng; Tsai, Keng-Chang; Chen, Chinpan

    2017-06-01

    Microbial infections of antibiotic-resistant strains cause serious diseases and have a significant impact on public health worldwide, so novel antimicrobial drugs are urgently needed. Insect venoms, a rich source of bioactive components containing antimicrobial peptides (AMPs), are attractive candidates for new therapeutic agents against microbes. Recently, a novel peptide, P1, identified from the venom of the Australian jumper ant Myrmecia pilosula, showed potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, but its structure-function relationship is unknown. Here, we used biochemical and biophysical techniques coupled with computational simulations to explore the mode of action of P1 interaction with dodecylphosphocholine (DPC) micelles as a model membrane system. Our circular dichroism (CD) and NMR studies revealed an amphipathic α-helical structure for P1 upon interaction with DPC micelles. A paramagnetic relaxation enhancement approach revealed that P1 orients its α-helix segment (F6-G14) into DPC micelles. In addition, the α-helix segment could be essential for membrane permeabilization and antimicrobial activity. Moreover, the arginine residues R8, R11, and R15 significantly contribute to helix formation and membrane-binding affinity. The lysine residue K19 of the C-terminus functionally guides P1 to interact with DPC micelles in the early interaction stage. Our study provides insights into the mode of action of P1, which is valuable in modifying and developing potent AMPs as antibiotic drugs.

  20. 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

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

    Science.gov (United States)

    Wiggins, H. V.; Eicken, H.; Fox, S. E.

    2012-12-01

    SEARCH is an interdisciplinary and interagency program that works with academic and government agency scientists to plan, conduct, and synthesize studies of arctic change. The vision of SEARCH is to provide scientific understanding of arctic environmental change to help society understand and respond to a rapidly changing Arctic. Towards this end, SEARCH: 1. Generates and synthesizes research findings and promotes arctic science and scientific discovery across disciplines and among agencies. 2. Identifies emerging issues in arctic environmental change. 3. Provides information resources to arctic stakeholders, policy-makers, and the public to help them respond to arctic environmental change. 4. Coordinates with national arctic science programs integral to SEARCH goals. 5. Facilitates research activities across local-to-global scales with stakeholder concerns incorporated from the start of the planning process. 6. Represents the U.S. arctic environmental change science community in international and global change research initiatives. Specific 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. Sea Ice for Walrus Outlook - a resource for Alaska Native subsistence hunters, coastal communities, and others that provides weekly reports with information on sea ice conditions relevant to walrus in Alaska waters. In April, the SEARCH Science Steering Committee (SSC) released a set of draft 5-year goals and objectives for review by the broader arctic science community. The goals and objectives will direct the SEARCH program in the next five years. The draft SEARCH goals focus on four areas: ice-diminished Arctic Ocean, warming

  2. "Bunched Black Swans" in Complex Geosystems: Cross-Disciplinary Approaches to the Additive and Multiplicative Modelling of Correlated Extreme Bursts

    Science.gov (United States)

    Watkins, N. W.; Rypdal, M.; Lovsletten, O.

    2012-12-01

    For all natural hazards, the question of when the next "extreme event" (c.f. Taleb's "black swans") is expected is of obvious importance. In the environmental sciences users often frame such questions in terms of average "return periods", e.g. "is an X meter rise in the Thames water level a 1-in-Y year event ?". Frequently, however, we also care about the emergence of correlation, and whether the probability of several big events occurring in close succession is truly independent, i.e. are the black swans "bunched". A "big event", or a "burst", defined by its integrated signal above a threshold, might be a single, very large, event, or, instead, could in fact be a correlated series of "smaller" (i.e. less wildly fluctuating) events. Several available stochastic approaches provide quantitative information about such bursts, including Extreme Value Theory (EVT); the theory of records; level sets; sojourn times; and models of space-time "avalanches" of activity in non-equilibrium systems. Some focus more on the probability of single large events. Others are more concerned with extended dwell times above a given spatiotemporal threshold: However, the state of the art is not yet fully integrated, and the above-mentioned approaches differ in fundamental aspects. EVT is perhaps the best known in the geosciences. It is concerned with the distribution obeyed by the extremes of datasets, e.g. the 100 values obtained by considering the largest daily temperature recorded in each of the years of a century. However, the pioneering work from the 1920s on which EVT originally built was based on independent identically distributed samples, and took no account of memory and correlation that characterise many natural hazard time series. Ignoring this would fundamentally limit our ability to forecast; so much subsequent activity has been devoted to extending EVT to encompass dependence. A second group of approaches, by contrast, has notions of time and thus possible non

  3. Catalyzing Cross-Disciplinary Research and Education Within and Beyond the Environmental and Geosciences to Address Emerging, Societally-Relevant Issues

    Science.gov (United States)

    Cak, A. D.; Vigdor, L. J.; Vorosmarty, C. J.; Giebel, B. M.; Santistevan, C.; Chasteau, C.

    2017-12-01

    Tackling emergent, societally-relevant problems in the environmental sciences is hardly confined to a single research discipline, but rather requires collaborations that bridge diverse domains and perspectives. While new technologies (e.g., Skype) can in theory unite otherwise geographically distributed participation in collaborative research, physical distance nevertheless raises the bar on intellectual dialogue. Such barriers may reveal perceptions of or real differences across disciplines, reflecting particular traditions in their histories and academic cultures. Individual disciplines are self-defined by their scientific, epistemologic, methodologic, or philosophical traditions (e.g., difficulties in understanding processes occurring at different scales, insufficient research funding for interdisciplinary work), or cultural and discursive hurdles (e.g., navigating a new field's jargon). Coupled with these challenges is a considerable deficiency in educating the next generation of scientists to help them develop a sufficient comfort level with thinking critically across multiple disciplinary domains and conceptual frameworks. To address these issues, the City University of New York (CUNY), the largest public urban university in the U.S., made a significant investment in advancing cross-disciplinary research and education, culminating in the opening of the CUNY Advanced Science Research Center (ASRC) in New York City (NYC) in late 2014. We report here on our experiences incubating new collaborative efforts to address environmental science-related research as it is interwoven with the ASRC's five research initiatives (Environmental Sciences, Neuroscience, Structural Biology, Photonics, and Nanoscience). We describe the ASRC's overall structure and function as both a stand-alone interdisciplinary center and one that collaborates more broadly with CUNY's network of twenty-four campuses distributed across NYC's five boroughs. We identify challenges we have faced so

  4. Design thinking - crossing disciplinary borders

    CSIR Research Space (South Africa)

    Viljoen, NM

    2009-01-01

    Full Text Available as to call this loss with reality a ‘mathematical masturbation’. (This is particularly evident in the history of American OR society and to date American OR is deemed more ‘mathematical’ while European and British OR are more ‘practical’.) This perceived...

  5. 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.

  6. Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

    Science.gov (United States)

    Da Rocha, Mitscheli Sanches; Arnold, Lora L; De Oliveira, Maria Luiza Cotrim Sartor; Catalano, Shadia M Ihlaseh; Cardoso, Ana Paula Ferragut; Pontes, Merielen G N; Ferrucio, Bianca; Dodmane, Puttappa R; Cohen, Samuel M; De Camargo, João Lauro V

    2014-05-01

    Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

  7. Physiology of inactivation of microbial cells by near-ultraviolet light: mode of action and application for the enrichment of mutants of Escherichia coli and saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Peters, J.

    1976-01-01

    The mode of action of near-ultraviolet (NUV) light was studied in Escherichia coli. NUV light (maximum emission at 365 nm) caused the photodestruction of ribonucleoside diphosphate (RDP) reductase activity in vivo. Evidence was presented for a model suggesting that the loss of RDP-reductase resulted in a metabolic state analogous to that produced during starvation for thymine. Some important properties of cells irradiated by NUV light, cell death, loss of the ability to support the replication of DNA phages and a delay in the onset of cell division in sublethally irradiated cells, were accounted for in terms of photoinactivation of RDP-reductase. Conditions were described under which NUV light was an effective counterselective agent for the enrichment of mutants of Escherichia coli and Saccharomyces cerevisiae

  8. 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.

  9. 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.

  10. Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery.

    Science.gov (United States)

    Jia, Zhilong; Liu, Ying; Guan, Naiyang; Bo, Xiaochen; Luo, Zhigang; Barnes, Michael R

    2016-05-27

    Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and

  11. 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.

  12. 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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 (Φ PSII , q P 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. - Highlights: • The EDU concentration of 300 mg L −1 should be considered as NOEL. • EDU concentrations ≥600 mg L −1 should not be applied to uncontrolled environments. • Hormetic responses indicate overcompensation in response to homeostasis disruption. - Ethylene diurea is not toxic to sensitive organisms when applied at low concentrations (practically < 600 mg L −1 ).

  13. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Science.gov (United States)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  14. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    International Nuclear Information System (INIS)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

  15. 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.

  16. 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

  17. 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.

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

    International Nuclear Information System (INIS)

    Matos, Pedro M.; Freitas, Teresa; Castanho, Miguel A.R.B.; Santos, Nuno C.

    2010-01-01

    Research highlights: → Sifuvirtide interacts with erythrocyte and lymphocyte membrane in a concentration dependent manner by decreasing its dipole potential. → Dipole potential variations in lipid vesicles show sifuvirtide's lipid selectivity towards saturated phosphatidylcholines. → 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.

  19. Medicinal Chemistry of the Anti-Diabetic Effects of Momordica Charantia: Active Constituents and Modes of Actions

    Science.gov (United States)

    Singh, Jaipaul; Cumming, Emmanuel; Manoharan, Gunasekar; Kalasz, Huba; Adeghate, Ernest

    2011-01-01

    Diabetes mellitus (DM) is one of the oldest known human disease currently affecting more than 200 million people worldwide. Diabetes mellitus is derived from two Greek words meaning siphon and sugar. In DM, patients have high blood level of glucose and this passes out with urine. This is because the endocrine pancreas does not produce either or not enough insulin or the insulin which is produced is not exerting its biochemical effect (or insulin resistance) effectively. Insulin is a major metabolic hormone which has numerous functions in the body and one main role is to stimulate glucose uptake into body’s cells where it is utilized to provide energy. The disease is classified into type 1 and type 2 DM. Type 1 DM develops when the insulin producing β cells have been destroyed and are unable to produce insulin. This is very common in children and is treated with insulin. Type 2 DM (T2DM) develops when the body is unable to produce an adequate amount of insulin or the insulin which is provided does not work efficiently. This is due to life style habits including unhealthy diet, obesity, lack of exercise and hereditary and environmental factors. Some symptoms of DM include excess urination, constant thirst, lethargy, weight loss, itching, decreased digestive enzyme secretion, slow wound healing and other related symptoms. If left untreated, DM can result in severe long-term complications such as kidney and heart failure, stroke, blindness, nerve damage, exocrine glands insufficiency and other forms of complications. T2DM can be treated and controlled by prescribed drugs, regular exercise, diet (including some plant-based food) and general change in life style habits. This review is concerned with the role of plant-based medicine to treat DM. One such plant is Momordica charantia which is grown in tropical countries worldwide and it has been used as a traditional herbal medicine for thousands of years although its origin in unknown. This review examines the

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

    Directory of Open Access Journals (Sweden)

    Xueling Zheng

    Full Text Available 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.

  1. Toxicity and mode of action of tritium alone and mixed with copper on the green algae Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Rety, Celine

    2010-01-01

    Liquid releases by Nuclear Power Plants (NPP) are composed of a mixture of radioactive and non-radioactive substances. When organisms are exposed to mixtures of contaminants the resultant toxicity can be enhanced, or reduced, due to interactions. In order to identify potential interactions between substances released by NPP, two substances representative of such effluents (in term of toxicity and of quantity) were selected for studies: Tritiated water (HTO) and copper (Cu). Effects of this binary mixture were studied on the unicellular green algae Chlamydomonas reinhardtii. HTO, when examined along, was not very toxic to C. reinhardtii. The most sensitive and early effect of HTO was an increase in oxidative stress at concentrations of 40 kBq mL -1 (0.13 μGy h -1 ). Algae exposure to the binary mixture HTO/Cu induced interactive effects on oxidative stress. Reactive Oxygen Species production was higher from exposure to the mixture of contaminants than the addition of the effect from each substance individually. This interaction was explained by an enhanced copper uptake by the algae when in the presence of HTO. The observed supra-additive effect could also be due to direct toxic interactions, especially on the antioxidant system. To conclude, this study showed that the effects of a mixture of radioactive and nonradioactive substances can be greater than what would be predicted based on mere addition of individual effects. Even thought this binary mixture is just a small part of NPP effluents, the study showed that potential interactions should be considered when determining ecological risks to aquatic ecosystems from NPP effluents. (author)

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Application of benchmark dose modeling to protein expression data in the development and analysis of mode of action/adverse outcome pathways for testicular toxicity.

    Science.gov (United States)

    Chepelev, Nikolai L; Meek, M E Bette; Yauk, Carole Lyn

    2014-11-01

    Reliable quantification of gene and protein expression has potential to contribute significantly to the characterization of hypothesized modes of action (MOA) or adverse outcome pathways for critical effects of toxicants. Quantitative analysis of gene expression by benchmark dose (BMD) modeling has been facilitated by the development of effective software tools. In contrast, protein expression is still generally quantified by a less robust effect level (no or lowest [adverse] effect levels) approach, which minimizes its potential utility in the consideration of dose-response and temporal concordance for key events in hypothesized MOAs. BMD modeling is applied here to toxicological data on testicular toxicity to investigate its potential utility in analyzing protein expression relevant to the proposed MOA to inform human health risk assessment. The results illustrate how the BMD analysis of protein expression in animal tissues in response to toxicant exposure: (1) complements other toxicity data, and (2) contributes to consideration of the empirical concordance of dose-response relationships, as part of the weight of evidence for hypothesized MOAs to facilitate consideration and application in regulatory risk assessment. Lack of BMD analysis in proteomics has likely limited its use for these purposes. This paper illustrates the added value of BMD modeling to support and strengthen hypothetical MOAs as a basis to facilitate the translation and uptake of the results of proteomic research into risk assessment. Copyright © 2014 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology © 2014 John Wiley & Sons, Ltd.

  7. 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.

  8. A structure-activity relationship study on a natural germination inhibitor, 2-methoxy-4-vinylphenol (MVP), in wheat seeds to evaluate its mode of action.

    Science.gov (United States)

    Darabi, Hossein Reza; Mohandessi, Shabnam; Balavar, Yadollah; Aghapoor, Kioumars

    2007-01-01

    The first aim of the present study was to evaluate which structural elements of the 2-methoxy-4-vinylphenol (MVP) molecule (1) are responsible for its observed activity as germination inhibitor in wheat seeds. To find its mode of action, a series of compounds with varying functional moieties and substitution patterns were prepared and evaluated for their inhibitory activity. This systematic competitive inhibition study characterized two criteria for the effective increase of the inhibiting ability: (i) ortho substitution to each of the hydroxy and methoxy groups; (ii) alkene moiety on the ring. Understanding how the structure of natural compounds relates to their inhibition function is fundamentally important and may help to facilitate their application as novel inhibitors to restrain preharvest sprouting (PHS) in wheat fields. In this regard, in MVP and its natural analogues 8 and 9 as the most active inhibitors, the ortho substitution of hydroxy and methoxy groups plays a key role in their activity and, as well, the alkene moiety influences the activity significantly.

  9. Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5-dichlorophenol to adverse outcomes in Lemna minor.

    Science.gov (United States)

    Xie, Li; Gomes, Tânia; Solhaug, Knut Asbjørn; Song, You; Tollefsen, Knut Erik

    2018-04-01

    Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Efficacy and mode of action of a noise-sensor light alarm to decrease noise in the pediatric intensive care unit: a prospective, randomized study.

    Science.gov (United States)

    Jousselme, Chloé; Vialet, Renaud; Jouve, Elisabeth; Lagier, Pierre; Martin, Claude; Michel, Fabrice

    2011-03-01

    To determine whether a sound-activated light-alarm device could reduce the noise in the central area of our pediatric intensive care unit and to determine whether this reduction was significant enough to decrease the noise that could be perceived by a patient located in a nearby room. The secondary objective was to determine the mode of action of the device. In a 16-bed pediatric and neonatal intensive care unit, a large and clearly noticeable sound-activated light device was set in the noisiest part of the central area of our unit, and noise measurements were made in the central area and in a nearby room. In a prospective, quasi-experimental design, sound levels were compared across three different situations--no device present, device present and turned on, and device present but turned off--and noise level measurements were made over a total of 18 days. None. Setting a sound-activated light device on or off. When the device was present, the noise was about 2 dB lower in the central area and in a nearby room, but there was no difference in noise level with the device turned on vs. turned off. The noise decrease in the central area was of limited importance but was translated in a nearby room. The sound-activated light device did not directly decrease noise when turned on, but repetition of the visual signal throughout the day raised staff awareness of noise levels over time.

  11. 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.

  12. 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.

  13. 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

  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. 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

  16. A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands.

    Science.gov (United States)

    Matsukawa, Jun; Hori, Yasunobu; Nishida, Haruyuki; Kajino, Masahiro; Inatomi, Nobuhiro

    2011-05-01

    TAK-438 is a novel potassium-competitive acid blocker (P-CAB) type antisecretory agent that reversibly inhibits gastric H+, K+-ATPase. Previously, we showed that TAK-438 has superior efficacy compared to lansoprazole, a proton pump inhibitor, in the inhibition of acid secretion in vivo. In this study, we investigated the differences in the mode of actions of the two drugs using primary cultured rabbit gastric glands. TAK-438 and lansoprazole inhibited gastric acid formation in acutely isolated gastric glands (IC₅₀) values, 0.30 and 0.76 μM, respectively). In cultured gastric glands that were preincubated with TAK-438, the inhibitory effect on forskolin-stimulated acid formation was augmented over the incubation period, whereas the inhibitory effect of lansoprazole was not affected by time of incubation. Next, we evaluated the durations of the actions of TAK-438 and lansoprazole after gastric glands were incubated with either drug for 2h followed by washout. Even 8h after the drug washout, TAK-438 at higher concentrations inhibited acid formation, but the inhibitory effect of lansoprazole disappeared immediately after washout. Additionally, only a small amount of [¹⁴C] lansoprazole accumulated in resting glands, and this accumulation was enhanced by treatment with 1 μM of forskolin. In contrast, high levels of [¹⁴C] TAK-438 accumulated in both resting and forskolin-treated glands. Furthermore, a 2-h preincubation followed by washout demonstrated a slow clearance of [¹⁴C] TAK-438 from the glands. These findings suggest that TAK-438 exerts a longer and more potent antisecretory effect than lansoprazole as a result of its high accumulation and slow clearance from the gastric glands. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Evaluation of the human relevance of the constitutive androstane receptor-mediated mode of action for rat hepatocellular tumor formation by the synthetic pyrethroid momfluorothrin.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Kikumoto, Hiroko; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Cohen, Samuel M; Lake, Brian G; Yamada, Tomoya

    2017-01-01

    High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations. The effect of sodium phenobarbital (NaPB), a prototypic rodent hepatocarcinogen with a CAR-mediated MOA, was also investigated. Human hepatocyte growth factor (hHGF) produced a concentration-dependent increase in replicative DNA synthesis in rat and human hepatocytes. However, while NaPB and momfluorothrin increased replicative DNA synthesis in rat hepatocytes, NaPB, momfluorothrin and Z-CMCA did not increase replicative DNA synthesis in human hepatocytes. NaPB, momfluorothrin and Z-CMCA increased CYP2B1/2 mRNA levels in rat hepatocytes. NaPB and momfluorothrin also increased CYP2B6 mRNA levels in human hepatocytes. Overall, while momfluorothrin and NaPB activated CAR in cultured human hepatocytes, neither chemical increased replicative DNA synthesis. Furthermore, to confirm whether the findings observed in vitro were also observed in vivo, a humanized chimeric mouse study was conducted. Replicative DNA synthesis was not increased in human hepatocytes of chimeric mice treated with momfluorothrin or its close structural analogue metofluthrin. As human hepatocytes are refractory to the mitogenic effects of momfluorothrin, in contrast to rat hepatocytes, the data support the hypothesis that the MOA for momfluorothrin-induced rat liver tumor formation is not relevant for humans.

  18. 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

  19. 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

  20. Editor's Highlight: Mode of Action Analysis for Rat Hepatocellular Tumors Produced by the Synthetic Pyrethroid Momfluorothrin: Evidence for Activation of the Constitutive Androstane Receptor and Mitogenicity in Rat Hepatocytes.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Sumida, Kayo; Nagahori, Hirohisa; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Lake, Brian G; Cohen, Samuel M; Yamada, Tomoya

    2017-08-01

    High dietary levels of momfluorothrin, a nongenotoxic synthetic pyrethroid, induced hepatocellular tumors in male and female Wistar rats in a 2-year bioassay. The mode of action (MOA) for rat hepatocellular tumors was postulated to occur via activation of the constitutive androstane receptor (CAR), as momfluorothrin is a close structural analogue of the pyrethroid metofluthrin, which is known to produce rat liver tumors through a CAR-mediated MOA. To elucidate the MOA for rat hepatocellular tumor formation by momfluorothrin, this study was conducted to examine effects on key and associative events of the CAR-mediated MOA for phenobarbital based on the International Programme on Chemical Safety framework. A 2-week in vivo study in Wistar rats revealed that momfluorothrin induced CYP2B activities, increased liver weights, produced hepatocyte hypertrophy and increased hepatocyte replicative DNA synthesis. These effects correlated with the dose-response relationship for liver tumor formation and also showed reversibility upon cessation of treatment. Moreover, momfluorothrin did not increase CYP2B1/2 mRNA expression and hepatocyte replicative DNA synthesis in CAR knockout rats. Using cultured Wistar rat hepatocytes and the RNA interference technique, knockdown of CAR resulted in a suppression of induction of CYP2B1/2 mRNA levels by momfluorothrin. Alternative MOAs for liver tumor formation were excluded. A global gene expression profile analysis of the liver of male Wistar rats treated with momfluorothrin for 2 weeks also showed similarity to the prototypic CAR activator phenobarbital. Overall, these data strongly support that the postulated MOA for momfluorothrin-induced rat hepatocellular tumors as being mediated by CAR activation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. 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

  2. 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

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... 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...

  3. Karg, S. New projects within the FLAX Network. In: Karg S. (ed.) Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the second

    DEFF Research Database (Denmark)

    Karg, Sabine

    2010-01-01

    Karg, S. New projects within the FLAX Network. In: Karg S. (ed.) Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the second workshop 28...

  4. Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the first workshop 24-26 November 2009 in the Carlsberg Academy Copenhagen, Denmark

    DEFF Research Database (Denmark)

    Karg, Sabine

    Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the first workshop 24-26 November 2009 in the Carlsberg Academy Copenhagen, Denmark...

  5. Karg S. (ed.) Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the second workshop 28-30 June 2010 at Sonnerupgaard and in the Land

    DEFF Research Database (Denmark)

    Karg, Sabine

    2010-01-01

    Karg S. (ed.) Flax (Linum usitatissimum L.) - a natural resource for food and textiles for 8000 years. Cross-disciplinary investigations on the evolution and cultural history of flax and linen. Programme and abstracts of the second workshop 28-30 June 2010 at Sonnerupgaard and in the Land...

  6. 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

  7. Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells.

    Science.gov (United States)

    Bodero, Marcia; Hoogenboom, Ron L A P; Bovee, Toine F H; Portier, Liza; de Haan, Laura; Peijnenburg, Ad; Hendriksen, Peter J M

    2018-02-01

    A study with DNA microarrays was performed to investigate the effects of two diarrhetic and one azaspiracid shellfish poison, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and azaspiracid-1 (AZA-1) respectively, on the whole-genome mRNA expression of undifferentiated intestinal Caco-2 cells. Previously, the most responding genes were used to develop a dedicated array tube test to screen shellfish samples on the presence of these toxins. In the present study the whole genome mRNA expression was analyzed in order to reveal modes of action and obtain hints on potential biomarkers suitable to be used in alternative bioassays. Effects on key genes in the most affected pathways and processes were confirmed by qPCR. OA and DTX-1 induced almost identical effects on mRNA expression, which strongly indicates that OA and DTX-1induce similar toxic effects. Biological interpretation of the microarray data indicates that both compounds induce hypoxia related pathways/processes, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. The gene expression profile of AZA-1 is different and shows increased mRNA expression of genes involved in cholesterol synthesis and glycolysis, suggesting a different mode of action for this toxin. Future studies should reveal whether identified pathways provide suitable biomarkers for rapid detection of DSPs in shellfish. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Metabonomic strategy for the investigation of the mode of action of the phytotoxin (5S,8R,13S,16R)-(-)-pyrenophorol using 1H nuclear magnetic resonance fingerprinting.

    Science.gov (United States)

    Aliferis, Konstantinos A; Chrysayi-Tokousbalides, Maria

    2006-03-08

    The biochemical mode of action of (5S,8R,13S,16R)-(-)-pyrenophorol isolated from a Drechslera avenae pathotype was investigated by using metabolic fingerprinting. (1)H NMR spectra of crude leaf extracts from untreated Avena sterilis seedlings and A. sterilis seedlings treated with pyrenophorol were compared with those obtained from treatments with the herbicides diuron, glyphosate, mesotrione, norflurazon, oxadiazon, and paraquat. Multivariate analysis was carried out to group treatments according to the mode of action of the phytotoxic substances applied. Analysis results revealed that none of the herbicide treatments fitted the pyrenophorol model and indicate that the effect of the phytotoxin on A. sterilis differs than those caused by glyphosate, mesotrione, norflurazon, oxadiazon, paraquat, and diuron, which inhibit 5-enolpyruvylshikimate-3-phosphate synthase, 4-hydroxyphenyl-pyruvate-dioxygenase, phytoene desaturase, protoporphyrinogen oxidase, photosystem I, and photosystem II, respectively. The method applied, combined with appropriate data preprocessing and analysis, was found to be rapid for the screening of phytotoxic substances for metabolic effects.

  9. Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.

    Science.gov (United States)

    Ozdemir, Vural; Williams-Jones, Bryn; Graham, Janice E; Preskorn, Sheldon H; Gripeos, Dimitrios; Glatt, Stephen J; Friis, Robert H; Reist, Christopher; Szabo, Sandor; Lohr, James B; Someya, Toshiyuki

    2007-04-01

    Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

  10. Modelling the fate of hydrophobic organic contaminants in a boreal forest catchment: A cross disciplinary approach to assessing diffuse pollution to surface waters

    International Nuclear Information System (INIS)

    Bergknut, Magnus; Meijer, Sandra; Halsall, Crispin; Agren, Anneli; Laudon, Hjalmar; Koehler, Stephan; Jones, Kevin C.; Tysklind, Mats; Wiberg, Karin

    2010-01-01

    The fate of hydrophobic organic compounds (HOCs) in soils and waters in a northern boreal catchment was explored through the development of a chemical fate model in a well-characterised catchment system dominated by two land types: forest and mire. Input was based solely on atmospheric deposition, dominated by accumulation in the winter snowpack. Release from soils was governed by the HOC concentration in soil, the soil organic carbon fraction and soil-water DOC content. The modelled export of selected HOCs in surface waters ranged between 11 and 250 ng day -1 during the snow covered period, compared to 200 and 9600 ng/d during snow-melt; highlighting the importance of the snow pack as a source of these chemicals. The predicted levels of HOCs in surface water were in reasonable agreement to a limited set of measured values, although the model tended to over predict concentrations of HOCs for the forested sub-catchment, by over an order of magnitude in the case of hexachlorobenzene and PCB 180. This possibly reflects both the heterogeneity of the forest soils and the complicated and changing hydrology experienced between the different seasons. - The fate of hydrophobic organic contaminants in a boreal forest catchment is connected to the flux of dissolved organic carbon and seasonal deposition.

  11. Cross-disciplinary links in environmental systems science: Current state and claimed needs identified in a meta-review of process models.

    Science.gov (United States)

    Ayllón, Daniel; Grimm, Volker; Attinger, Sabine; Hauhs, Michael; Simmer, Clemens; Vereecken, Harry; Lischeid, Gunnar

    2018-05-01

    Terrestrial environmental systems are characterised by numerous feedback links between their different compartments. However, scientific research is organized into disciplines that focus on processes within the respective compartments rather than on interdisciplinary links. Major feedback mechanisms between compartments might therefore have been systematically overlooked so far. Without identifying these gaps, initiatives on future comprehensive environmental monitoring schemes and experimental platforms might fail. We performed a comprehensive overview of feedbacks between compartments currently represented in environmental sciences and explores to what degree missing links have already been acknowledged in the literature. We focused on process models as they can be regarded as repositories of scientific knowledge that compile findings of numerous single studies. In total, 118 simulation models from 23 model types were analysed. Missing processes linking different environmental compartments were identified based on a meta-review of 346 published reviews, model intercomparison studies, and model descriptions. Eight disciplines of environmental sciences were considered and 396 linking processes were identified and ascribed to the physical, chemical or biological domain. There were significant differences between model types and scientific disciplines regarding implemented interdisciplinary links. The most wide-spread interdisciplinary links were between physical processes in meteorology, hydrology and soil science that drive or set the boundary conditions for other processes (e.g., ecological processes). In contrast, most chemical and biological processes were restricted to links within the same compartment. Integration of multiple environmental compartments and interdisciplinary knowledge was scarce in most model types. There was a strong bias of suggested future research foci and model extensions towards reinforcing existing interdisciplinary knowledge rather than

  12. Cross-Disciplinary Scientific Foundation for Sustainability

    DEFF Research Database (Denmark)

    Fast, Alf Michael; Clark, Woodrow

    2017-01-01

    , they are adamantly opposed to a Lifeworld view of economics. The objectivist's paradigm in a pre–mass production globalized world provides little guidance in terms of uneven economic growth and clearly substantive problems with understanding the needs of developing nations. Instead, it argues that “market forces...

  13. 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

  14. 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.

  15. 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

  16. 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.

    Science.gov (United States)

    Sanderson, Hans; Thomsen, Marianne

    2009-06-01

    Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under 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 data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

  17. Anti-methicillin Resistant Staphylococcus aureus Compound Isolation from Halophilic Bacillus amyloliquefaciens MHB1 and Determination of Its Mode of Action Using Electron Microscope and Flow Cytometry Analysis

    OpenAIRE

    Jeyanthi, Venkadapathi; Velusamy, Palaniyandi

    2016-01-01

    The aim of this study was to purify, characterize and evaluate the antibacterial activity of bioactive compound against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA compound was produced by a halophilic bacterial strain designated as MHB1. The MHB1 strain exhibited 99��% similarity to Bacillus amyloliquefaciens based on 16S rRNA gene analysis. The culture conditions of Bacillus amyloliquefaciens MHB1 were optimized using nutritional and environmental parameters for enhanc...

  18. 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.

  19. 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.

  20. Anti-methicillin Resistant Staphylococcus aureus Compound Isolation from Halophilic Bacillus amyloliquefaciens MHB1 and Determination of Its Mode of Action Using Electron Microscope and Flow Cytometry Analysis.

    Science.gov (United States)

    Jeyanthi, Venkadapathi; Velusamy, Palaniyandi

    2016-06-01

    The aim of this study was to purify, characterize and evaluate the antibacterial activity of bioactive compound against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA compound was produced by a halophilic bacterial strain designated as MHB1. The MHB1 strain exhibited 99 % similarity to Bacillus amyloliquefaciens based on 16S rRNA gene analysis. The culture conditions of Bacillus amyloliquefaciens MHB1 were optimized using nutritional and environmental parameters for enhanced anti-MRSA compound production. The pure bioactive compound was isolated using silica gel column chromatography and Semi-preparative High-performance liquid chromatography (Semi-preparative HPLC). The Thin layer chromatography, Fourier transform infrared spectroscopy and proton NMR ((1)H NMR) analysis indicated the phenolic nature of the compound. The molecular mass of the purified compound was 507 Da as revealed by Liquid chromatography-mass spectrometry (LC-MS) analysis. The compound inhibited the growth of MRSA with minimum inhibitory concentration (MIC) of 62.5 µg mL(-1). MRSA bacteria exposed to 4× MIC of the compound and the cell viability was determined using flow cytometric analysis. Scanning electron microscope and Transmission electron microscope analysis was used to determine the ultrastructural changes in bacteria. This is the first report on isolation of anti-MRSA compound from halophilic B. amyloliquefaciens MHB1 and could act as a promising biocontrol agent.

  1. 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.

  2. Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.

    Science.gov (United States)

    Esposito, Francesca; Mandrone, Manuela; Del Vecchio, Claudia; Carli, Ilaria; Distinto, Simona; Corona, Angela; Lianza, Mariacaterina; Piano, Dario; Tacchini, Massimo; Maccioni, Elias; Cottiglia, Filippo; Saccon, Elisa; Poli, Ferruccio; Parolin, Cristina; Tramontano, Enzo

    2017-08-31

    Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors. Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function. We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket. On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol. Results supported the potential of this plant as a valuable multitarget active drug source. In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  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. From toxicological problem to therapeutic use: the discovery of the mode of action of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), its toxicology and development as a drug.

    Science.gov (United States)

    Lock, E A; Ellis, M K; Gaskin, P; Robinson, M; Auton, T R; Provan, W M; Smith, L L; Prisbylla, M P; Mutter, L C; Lee, D L

    1998-08-01

    NTBC is a triketone with herbicidal activity that has been shown to have a novel mode of action by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase in plants. Early studies on the toxicity of this compound found that rats treated with NTBC developed corneal lesions. Investigations aimed at understanding the mechanistic basis for the ocular toxicity discovered that the rats developed tyrosinaemia and excreted large amounts of 4-hydroxyphenylpyruvate and 4-hydroxyphenyllactate, owing to inhibition of the hepatic enzyme 4-hydroxyphenylpyruvate dioxygenase. The corneal lesions resemble those seen when rats are fed a diet supplemented with tyrosine, leading us to conclude that the ocular toxicity seen with NTBC is a consequence of a marked and sustained tyrosinaemia. Studies in collaboration with Professor Sven Lindstedt showed that NTBC was a potent inhibitor of purified human liver 4-hydroxyphenylpyruvate dioxygenase. This interaction lead to the concept of using NTBC to treat patients with tyrosinaemia type 1, to block or reduce the formation of toxic metabolites such as succinylacetoacetate in the liver. Zeneca Agrochemicals and Zeneca Pharmaceuticals made NTBC available for clinical use and, with the approval of the Swedish Medical Products Agency, a seriously ill child with an acute form of tyrosinaemia type 1 was successfully treated in February 1991. Subsequently, other children with this inborn error of metabolism in Sweden and other countries have been treated with NTBC. The drug is now available to those in need via Swedish Orphan AB.

  5. Nanoscaled boehmites' modes of action in a polymer and its carbon fiber reinforced plastic under compression load; Wirkungsweisen nanoskaliger Boehmite in einem Polymer und seinem Kohlenstofffaserverbund unter Druckbelastung

    Energy Technology Data Exchange (ETDEWEB)

    Arlt, Christine

    2011-07-01

    Increasing ecological awareness as well as quality and safety demands, which are present, for instance, in the aerospace and automotive sectors, lead to the need to use more sophisticated and more effective materials. For that purpose, laminates of carbon fiber reinforced plastic (CFRP), which are manufactured by injection technology, are reinforced with boehmite particles. This doping strengthens the laminates, whose original properties are weaker than prepregs. Besides the shear strength, compression strength and the damage tolerance, the mode of action of the nanoparticles in resin and in CRFP is also analyzed. It thereby reveals that the hydroxyl groups and even more a taurine modification of the boehmites' surface after the elementary polymer morphology. Consequently a new flow and reaction comportment, lower glass transition temperatures and shrinkage, as well as a changed mechanical behavior occur. Due to a structural upgrading of the matrix (higher shear stiffness, reduced residual stress), a better fiber-matrix adhesion, and differing crack paths, the boehmite nanoparticles move the degradation barrier of the material to higher loadings, thus resulting in considerably upgraded new CFRP. (orig.)

  6. Alleviative Effects of a Kampo (a Japanese Herbal Medicine “Maoto (Ma-Huang-Tang” on the Early Phase of Influenza Virus Infection and Its Possible Mode of Action

    Directory of Open Access Journals (Sweden)

    Takayuki Nagai

    2014-01-01

    Full Text Available A Kampo medicine, maoto, has been prescribed in an early phase of influenza-like illness and used for a treatment of influenza clinically in Japan these days. However, the efficacy of maoto against the virus infection remains to be elucidated. This study was conducted to evaluate the alleviative effects of maoto against early phase of influenza virus infection and its preliminary mode of actions through immune systems. When maoto (0.9 and 1.6 g/kg/day was orally administered to A/J mice on upper respiratory tract infection of influenza virus A/PR/8/34 from 4 hours to 52 hours postinfection (p.i. significant antipyretic effect was shown in comparison with water-treated control. Administration of maoto (0.8 and 1.3 g/kg/day significantly decreased the virus titers in both nasal (NLF and bronchoalveolar lavage fluids (BALF at 52 hours p.i., and significantly increased the anti-influenza virus IgM, IgA, and IgG1 antibody titers in NLF, BALF, and serum, respectively. Maoto also increased significantly the influenza virus-bound IgG1 and IgM antibody titers in serum and the virus-bound IgM antibody titer in even the BALF of uninfected A/J mice. These results indicate that maoto exerts antipyretic activity in influenza virus-infected mice and virus reducing effect at an early phase of the infection through probably augmentation of the virus-bound natural antibodies.

  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. DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer Thapsigargin based on comparative gene expression profiling in Jurkat T cells

    NARCIS (Netherlands)

    Schmeits, P.C.J.; Katika, M.R.; Peijnenburg, A.A.C.M.; Loveren, van H.; Hendriksen, P.J.M.

    2014-01-01

    Previously, we studied the effects of deoxynivalenol (DON) and tributyltin oxide (TBTO) on whole genome mRNA expression profiles of human T lymphocyte Jurkat cells. These studies indicated that DON induces ribotoxic stress and both DON and TBTO induced ER stress which resulted into T-cell activation

  10. Low Power and High Sensitivity MOSFET-Based Pressure Sensor

    International Nuclear Information System (INIS)

    Zhang Zhao-Hua; Ren Tian-Ling; Zhang Yan-Hong; Han Rui-Rui; Liu Li-Tian

    2012-01-01

    Based on the metal-oxide-semiconductor field effect transistor (MOSFET) stress sensitive phenomenon, a low power MOSFET pressure sensor is proposed. Compared with the traditional piezoresistive pressure sensor, the present pressure sensor displays high performances on sensitivity and power consumption. The sensitivity of the MOSFET sensor is raised by 87%, meanwhile the power consumption is decreased by 20%. (cross-disciplinary physics and related areas of science and technology)

  11. 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...

  12. Defining Extreme Events: A Cross-Disciplinary Review

    Science.gov (United States)

    McPhillips, Lauren E.; Chang, Heejun; Chester, Mikhail V.; Depietri, Yaella; Friedman, Erin; Grimm, Nancy B.; Kominoski, John S.; McPhearson, Timon; Méndez-Lázaro, Pablo; Rosi, Emma J.; Shafiei Shiva, Javad

    2018-03-01

    Extreme events are of interest worldwide given their potential for substantial impacts on social, ecological, and technical systems. Many climate-related extreme events are increasing in frequency and/or magnitude due to anthropogenic climate change, and there is increased potential for impacts due to the location of urbanization and the expansion of urban centers and infrastructures. Many disciplines are engaged in research and management of these events. However, a lack of coherence exists in what constitutes and defines an extreme event across these fields, which impedes our ability to holistically understand and manage these events. Here, we review 10 years of academic literature and use text analysis to elucidate how six major disciplines—climatology, earth sciences, ecology, engineering, hydrology, and social sciences—define and communicate extreme events. Our results highlight critical disciplinary differences in the language used to communicate extreme events. Additionally, we found a wide range in definitions and thresholds, with more than half of examined papers not providing an explicit definition, and disagreement over whether impacts are included in the definition. We urge distinction between extreme events and their impacts, so that we can better assess when responses to extreme events have actually enhanced resilience. Additionally, we suggest that all researchers and managers of extreme events be more explicit in their definition of such events as well as be more cognizant of how they are communicating extreme events. We believe clearer and more consistent definitions and communication can support transdisciplinary understanding and management of extreme events.

  13. 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…

  14. 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,"…

  15. 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.

  16. Developing Cross-Disciplinary Competencies through College Algebra

    Directory of Open Access Journals (Sweden)

    Reem Jaafar, PhD

    2012-08-01

    Full Text Available To argue for the importance of an integrative approach to learning in introductory STEM (Science, Technology, Engineering and Mathematics and other courses, we present a case study of a project incorporating cross-curricular skills in a college algebra course. We analyze student work on the project and responses to surveys, and find the assignment affects positively students’ mastery of specific quantitative skills, perceptions of learning, civic awareness, and sense of relevance of mathematical study. We use the analysis to suggest guidelines for designing other activities aiming to teach the whole student in introductory courses.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    by regulators and policy-makers, as it is reflected in the 80 billion Euro "Horizon 2020" EU Framework Programme for Research and Innovation. This programme puts special emphasis at breaking down barriers between fields to create a path breaking environment for knowledge, research and innovation. However...

  18. (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

    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...

  19. Enhancing evidence-based coaching through the development of a coaching psychology competency framework : focus on the coaching relationship.

    OpenAIRE

    Lai, Yi-Ling

    2015-01-01

    The overall aim of this thesis is to facilitate the development of evidence-based coaching through investigating a competency framework for Coaching Psychologists to enhance the coaching relationship towards a positive outcome. Coaching has been extensively applied to organisational and leadership development programmes in the past few decades. However, coaching is not an accredited profession because it is a cross-disciplinary methodology. There are still some gaps in the existing coaching r...

  20. Old plants newly discovered: Cassia sieberiana D.C. and Cassia abbreviata Oliv. Oliv. root extracts inhibit in vitro HIV-1c replication in peripheral blood mononuclear cells (PBMCs) by different modes of action.

    Science.gov (United States)

    Leteane, Melvin M; Ngwenya, Barbara N; Muzila, Mbaki; Namushe, Amos; Mwinga, John; Musonda, Rosemary; Moyo, Sikhulile; Mengestu, Yehualashete B; Abegaz, Berhanu M; Andrae-Marobela, Kerstin

    2012-05-07

    Despite advances in anti-retroviral therapy which has transformed HIV/AIDS from a fatal to a manageable chronic disease, increasing viral drug resistance, side effects and uneven access to anti-retroviral drugs remain considerable therapeutic challenges. Partly as a consequence of these shortcomings and partly based on the fact that HIV/AIDS gives rise to opportunistic infections whose symptoms have been managed in Africa in an HIV/AIDS-independent context by traditional healers for centuries, many HIV/AIDS patients use herbal medicines. The aim of this study was to screen selected medicinal plants from Botswana, used by traditional healers to treat/manage HIV/AIDS, for inhibitory activities on HIV replication. Based on an ethnomedical survey, ethanolic tannin-containing and tannin-free extracts from 10 medicinal plants were tested for inhibitory properties against a clone of HIV-1c (MJ(4)) measuring cytopathic effect protection and levels of viral p24 antigen in infected PBMCs. Cassia sieberiana D.C., Cassia abbreviata Oliv. Oliv. and Plumbago zeylanica L. extracts showed significant inhibition of HIV-1c (MJ(4)) replication. The inhibitory activity of the Plumbago zeylanica extract could be attributed to its tannin content. Anti-HIV activity of Cassia sieberiana root and bark extracts, and Cassia abbreviata root extracts occurred in a concentration-dependent manner with an effective concentration (EC(50)) of 65.1μg/ml, 85.3μg/ml and 102.8μg/ml, respectively. Experiments to elucidate possible mechanism(s) of action revealed that Cassia sieberiana root and bark extracts blocked HIV replication at its binding- (EC(50)=70.2μg/ml and 90.8μg/ml, respectively) and entry stage (EC(50)=88.9μg/ml and 100.5μg/ml, respectively) while Cassia abbreviata extracts did not. We report here for the first time a direct inhibitory effect on HIV-1c replication of extracts from two extremely popular medicinal plants, Cassia sieberiana and Cassia abbreviata. Considering the

  1. 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.

  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)

    Reactive oxygen species (ROS) generation and protein leakage from the bacterial cells induced by the extract were also evaluated. .... as well as MIC/MBC values of the extract were calculated. The results of the disc diffusion assay .... This work was supported by grants from the. Science and Technology Innovation Fund of.

  4. THE MODE OF ACTION OF SULFANILAMIDE ON STREPTOCOCCUS. II.

    Science.gov (United States)

    Gay, F P; Clark, A R; Street, J A; Miles, D W

    1939-04-30

    The precise mode of therapeutic action of sulfanilamide on streptococcus can be arrived at only by considering the sum total of factors that inhibit or favor the natural growth of the microorganism under the experimental conditions that obtain, whether in vivo or in vitro. Too sweeping conclusions have hitherto been drawn from the study of a single variable factor, such as an unfavorable temperature or the absence or presence of peptone. We have attempted here to analyze the factors that have hitherto been recognized and some new ones, but particularly the relationship of these factors to one another. The result obtained on adding sulfanilamide to the streptococcus in the test tube is usually bacteriostasis and not complete destruction of even small numbers of bacteria. This is on the condition that the suspending medium is a favorable one for the growth of the microorganism; the more growth-promoting the medium is the less the bacteriostasis. If, on the other hand, the medium is too poor, or one that in itself inhibits growth, the addition of sulfanilamide may lead to sterilization of the culture. The conditions for growth of the streptococcus in the body of the rabbit or mouse, depend on the strain of bacteria used, but are on the whole favorable. Defence, however, in the form of phagocytosis by both polymorphonuclear and by mononuclear cells is attempted even in the susceptible animal. When sulfanilamide is used to treat such an animal, or when sulfanilamide-grown (inhibited) streptococci are employed, phagocytosis is pronounced, whether studied in the test tube or in the animal body. In the rabbit the delay by sulfanilamide and resultant increased phagocytosis by polymorphonuclears allows mononuclear cells to accumulate and recovery may result. Sulfanilamide not only does not completely destroy the streptococcus but does not even impair its innate virulence. It acts upon the streptococcus not only by inhibiting growth but by a temporary inhibition of hemotoxin formation, but only under certain conditions. The drug does not neutralize hemotoxin already formed. No significant effect of sulfanilamide on the formation of leucocidin or fibrinolysin by streptococcus has been evident in our experiments. Sulfanilamide differs in one important respect from other drugs that are destructive either in the test tube or actually in the body, for protozoa and bacteria. Protozoa fix or adsorb arsenicals and acriflavine that kill them variably in vitro and in vivo. Streptococci fix both gentian violet and acriflavine, which dyes have marked destructive action in the test tube but are less effective in vivo. Sulfanilamide is not diminished at all by contact in vitro with large masses of streptococci, nor does the action of this drug render the microorganism more capable than untreated cocci to adsorb gentian violet or acriflavine, or to be destroyed by these highly bactericidal substances.

  5. Digital food activism: Values, expertise and modes of action

    OpenAIRE

    Eli, Karin; Schneider, Tanja; Dolan, Catherine; Ulijaszek, Stanley

    2018-01-01

    New information and communication technologies (ICTs) increasingly enable social action and civic organisation, on both local and global scales. Ranging from social media platforms such as Facebook and Twitter, to mobile apps such as Buycott, and to data sharing wiki platforms and hacktivist projects, the activist landscape is rapidly shifting, collapsing geographic boundaries to form new issue publics and fast, sometimes mercurial, collective action. Within these emerging digital platforms f...

  6. 4-Alkynylphenylsilatranes: Insecticidal activity, mammalian toxicity, and mode of action

    International Nuclear Information System (INIS)

    Horsham, M.A.; Palmer, C.J.; Cole, L.M.; Casida, J.E.

    1990-01-01

    4-Ethynyl- and 4-(prop-1-ynyl)phenylsilatranes [N(CH 2 CH 2 O) 3 SiR, R = C 6 H 4 -4-C triple-bond CH or C 6 H 4 -4-C triple-bond CCH 3 ] are highly toxic to houseflies (pretreated with piperonyl butoxide) and milkweed bugs (topical LD 50 s 3-14 μg/g) and to mice (intraperitoneal LD 50 s 0.4-0.9 mg/kg), and they are moderately potent inhibitors of the [ 35 S]-tert-butylbicyclophosphorothionate or TBPS binding site (GABA-gated chloride channel) of mouse brain membranes. Scatchard analysis indicates noncompetitive interaction of 4-ethynylphenylsilatrane with the TBPS binding site. Phenylsilatrane analogues with 4-substituents of H, CH 3 , Cl, Br, and C triple-bond CSi(CH 3 ) 3 are highly toxic to mice but have little or no activity in the insect and receptor assays. Radioligand binding studies with [4- 3 H]phenylsilatrane failed to reveal a specific binding site in mouse brain. Silatranes with R = H, CH 3 , CH 2 Cl, CH double-bond CH 2 , OCH 2 CH 3 , and C 6 H 4 -4-CH 2 CH 3 are of little or no activity in the insect and mouse toxicity and TBPS binding site assays as are the trithia and monocyclic analogues of phenylsilatrane. 4-Alkynylphenylsilatranes are new probes to examine the GABA receptor-ionophore complex of insects and mammals

  7. Mode of action of Fusarium moniliforme endopolygalacturonase towards acetylated pectin.

    NARCIS (Netherlands)

    Bonnin, E.; Alebeek, van G.J.W.M.; Voragen, A.G.J.; Thibault, J.F.

    2003-01-01

    Endopolygalacturonase from Fusarium moniliforme was used to degrade acetylated homogalacturonan previously prepared from sugar beet pulp. The initial velocity and the final percentage of hydrolysis decreased-very rapidly with increasing degree of acetylation, showing that acetyl substitution

  8. Light Regulation of Gibberellin Biosynthesis and Mode of Action.

    Science.gov (United States)

    García-Martinez, José Luis; Gil, Joan

    2001-12-01

    Some phenotypic effects produced in plants by light are very similar to those induced by hormones. In this review, the light-gibberellin (GA) interaction in germination, de-etiolation, stem growth, and tuber formation (process regulated by GAs) are discussed. Germination of lettuce and Arabidopsis seeds depends on red irradiation (R), which enhances the expression of GA 3-oxidase genes (GA3ox) and leads to an increase in active GA content. De-etiolation of pea seedling alters the expression of GA20ox and GA3ox genes and induces a rapid decrease of GA1 content. Stem growth of green plants is also affected by diverse light irradiation characteristics. Low light intensity increases stem elongation and active GA content in pea and Brassica. Photoperiod controls active GA levels in long-day rosette (spinach and Silene) and in woody plants (Salix and hybrid aspen) by regulating different steps of GA biosynthesis, mainly through transcript levels of GA20ox and GA3ox genes. Light modulation of stem elongation in light-grown plants is controlled by phytochrome, which modifies GA biosynthesis and catabolism (tobacco, potato, cowpea, Arabidopsis) and GA-response (pea, cucumber, Arabidopsis). In Arabidopsis and tobacco, ATH1 (a gene encoding an homeotic transcription factor) is a positive mediator of a phyB-specific signal transduction cascade controlling GA levels by regulating the expression of GA20ox and GA3ox. Tuber formation in potato is controlled by photoperiod (through phyB) and GAs. Inductive short-day conditions alter the diurnal rhythm of GA20ox transcript abundance, and increases the expression of a new protein (PHOR1) that plays a role in the photoperiod-GA interaction.

  9. Mode of action of Organotins in Immune cells

    NARCIS (Netherlands)

    Hendriksen, P.J.M.; Schmeits, P.C.J.; Loveren, van H.; Shao, J.; Peijnenburg, A.A.C.M.

    2015-01-01

    This chapter focuses mainly on the effects of organotin compounds in various human and animal models and describes the research performed to elucidate the immunotoxic mechanism of action of organotin compounds. Both dibutyltin (DBT) and tributyltins (TBT) organotin compounds can cause atrophy of the

  10. Mode of action of new organic ammonium salts

    International Nuclear Information System (INIS)

    Miko, M.; Gulasova, A.; Devinsky, F.

    1998-01-01

    The aim of this paper was primary biochemical screening of cytotoxic activity. The measure of the cytotoxic effect was the degree of inhibition of 14 C-adenine and 14 C-valine incorporation into TCA-insoluble fraction of Ehrlich ascites carcinoma (EAC) cells. The primary biochemical screening was carried out with the 12 new organic ammonium salts (OAS), from a homologous series of N-alkyl-(N 2 -dodekanoylethyl)-dimethylammonium bromide. In a first approach to determine the model of action of the cytotoxic active compounds, the kinetics of DNA, RNA and protein synthesis inhibition were examined using isotope incorporation. On the basis of primary screening, one of the most active compounds, namely N-octyl-N 2 -dodekanoylethyl)-dimethylammonium bromide was chosen for further biochemical studies. Selected OAS inhibited biosynthesis of nucleic acids indicated by incorporation of 14 C-adenine and biosynthesis of protein indicated by incorporation of 14 C-valine. From the results, it is obvious, that the biosynthesis of DNA, indicated by the incorporation of 14 -thymidine, was more sensitive than biosynthesis of RNA indicated by the incorporation of 14 C-uridine. OAS at the lower concentrations stimulated aerobic glycolysis of tumor cells. Such a stimulation of glycolysis at lower concentrations of OAS indicated a potential interference with respiratory processes in tumor cells, or in isolated mitochondria. We assumed that the cytotoxic effect of OAS could be consequence of cytolytic activity of OAS. (authors)

  11. Mode of Action and Synergy of Ceftazidime and Baicalein against ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2015; 14 (4): 641-648 ... Results: The MIC of ceftazidime and baicalein against all the S. pyogenes strains were 0.50 and >. 256.0 µg/ml, respectively. .... against the S. pyogenes and S. aureus strains were performed ..... Resistance Genes and Some Virulence Factors in.

  12. Vasodilatation with pinacidil. Mode of action in rat resistance vessels

    International Nuclear Information System (INIS)

    Videbaek, L.M.; Aalkjaer, C.; Mulvany, M.J.

    1988-01-01

    Pinacidil is a newly developed antihypertensive vasodilator, proposed to belong to the new group of smooth muscle relaxants, the K+ channel openers. The in vitro effects of pinacidil on induced tone, smooth muscle membrane potential and 86 Rb and 42 K efflux from rat resistance vessels (internal diameter about 200 microns) were studied. Tone induced with noradrenaline was concentration-dependently inhibited by pinacidil. Responses to electrical field stimulation were also inhibited. However, tone induced with high K+ depolarization, noradrenaline in the presence of high K+, caffeine-induced contractions and noradrenaline contractions in the presence of felodipine were little affected by pinacidil. Pinacidil caused concentration-dependent hyperpolarisation of the resting smooth muscle. Pinacidil caused only a small and transient increase of the 86 Rb efflux rate constant, while the same concentrations of pinacidil produced a significant increase in the 42 K efflux rate constant. Our results seem to indicate that the relaxant effect of pinacidil is the result of an increase in K+ permeability, thus causing hyperpolarisation and relaxation. The opened K+ channels appear to be selective for K+ over Rb+

  13. [Modes of action of agrochemicals against plant pathogenic organisms].

    Science.gov (United States)

    Leroux, Pierre

    2003-01-01

    The chemical control of plant pathogens concerns mainly fungal diseases of crops. Most of the available fungicides act directly on essential fungal functions such as respiration, sterol biosynthesis or cell division. Consequently, these compounds can exhibit undesirable toxicological and environmental effects and sometimes select fungal resistant strains. Plant activators are expected to provide sustainable disease management in several crops because the development of resistance is not expected. Considering the future, the discovery of novel antifungal molecules will reap advantage from throughput screening methodologies and functional genomics.

  14. Mode of Action and Synergy of Ceftazidime and Baicalein against ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2015; 14 (4): 641-648 ... Revised accepted: 26 March 2015 ... Keywords: Streptococcus pyogenes, Cytoplasmic membrane permeability, ..... destroyed, with a resultant leak in the plasma.

  15. 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

  16. 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.

  17. Peptide antibiotics: discovery, modes of action, and applications

    National Research Council Canada - National Science Library

    Dutton, Christopher J

    2002-01-01

    ... and the application of biotechnology to many aspects of their development. While the origins of the peptides covered in this book are diverse, common themes can be readily identified. Peptides originally found in frogs and insects are now produced by bacterial fermentation, and site-directed mutagenesis has been brought to bear to produce novel ...

  18. Biostimulation of grapevine : mode of action and possible agronomic uses

    OpenAIRE

    Krzyzaniak, Yuko; Trouvelot, Sophie; Heloir, Marie-Claire; Fourquez, P.; Magnin-Robert, Jean-Bernard; Randoux, B.; Siah, A.; Halama, Patrice; Moreau, Emmanuelle; Adrian, Marielle

    2016-01-01

    Although there is a growing interest for the use of biostimulants in agriculture, only few methods allowing a precise description of their effects on plants have been reported. In the IRIS+ FUI project, two major and highly different worldwide crops, wheat (annual, monocotyledon) and grapevine (perennial, broadleaf), were chosen to deepen our knowledge of such compounds and explore their potential additional interest. The first objective is to develop in greenhouse conditions, a panel of tool...

  19. 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 ...

  20. Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid.

    Science.gov (United States)

    Li, Ning; Culton, Donna; Diaz, Luis A; Liu, Zhi

    2018-06-01

    Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 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

  2. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  3. 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

  4. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

    OpenAIRE

    Jiang, Shiyao; Tsikolia, Maia; 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...

  5. 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 LC 50 (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 LD 50 (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 EC 50 (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.

  6. 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.

  7. Antimicrobial activity of GN peptides and their mode of action

    DEFF Research Database (Denmark)

    Mojsoska, Biljana; Nielsen, Hanne Mørck; Jenssen, Håvard

    2016-01-01

    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......Increasing prevalence of bacteria that carries resistance towards conventional antibiotics has prompted the investigation into new compounds for bacterial intervention to ensure efficient infection control in the future. One group of potential lead structures for antibiotics is antimicrobial...

  8. 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.

  9. 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...... 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...

  10. 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...

  11. Highly Efficient PCDTBT:PC71 BM Based Photovoltaic Devices without Thermal Annealing Treatment

    International Nuclear Information System (INIS)

    Yang Shao-Peng; Kong Wei-Guang; Liu Bo-Ya; Fu Guang-Sheng; Zheng Wen-Yao; Li Bao-Min; Liu Xian-Hao

    2011-01-01

    We propose an effective method to fabricate highly efficient organic photovoltaic cells based on poly [N-9 - heptadecanyl-2, 7-carbazole-alt-5,5-(4'7'-di-2-thienyl-2'1'3-b-enzothiadiazole): [6,6]-phenyl C 71 -butyric acid methyl ester (PCDTBT:PC 71 BM). A power conversion efficiency of as high as 5.6% and a fill factor of 53.7% are achieved from the optimized cells. The influence of surface morphology of the active layer on the performance of the cells is also investigated. (cross-disciplinary physics and related areas of science and technology)

  12. [Standardization of the terms for Chinese herbal functions based on functional targeting].

    Science.gov (United States)

    Xiao, Bin; Tao, Ou; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

    2011-03-01

    Functional analysis concisely summarizes and concentrates on the therapeutic characteristics and features of Chinese herbal medicine. Standardization of the terms for Chinese herbal functions not only plays a key role in modern research and development of Chinese herbal medicine, but also has far-reaching clinical applications. In this paper, a new method for standardizing the terms for Chinese herbal function was proposed. Firstly, functional targets were collected. Secondly, the pathological conditions and the mode of action of every functional target were determined by analyzing the references. Thirdly, the relationships between the pathological condition and the mode of action were determined based on Chinese medicine theory and data. This three-step approach allows for standardization of the terms for Chinese herbal functions. Promoting the standardization of Chinese medicine terms will benefit the overall clinical application of Chinese herbal medicine.

  13. Genomics-based plant germplasm research (GPGR)

    Institute of Scientific and Technical Information of China (English)

    Jizeng Jia; Hongjie Li; Xueyong Zhang; Zichao Li; Lijuan Qiu

    2017-01-01

    Plant germplasm underpins much of crop genetic improvement. Millions of germplasm accessions have been collected and conserved ex situ and/or in situ, and the major challenge is now how to exploit and utilize this abundant resource. Genomics-based plant germplasm research (GPGR) or "Genoplasmics" is a novel cross-disciplinary research field that seeks to apply the principles and techniques of genomics to germplasm research. We describe in this paper the concept, strategy, and approach behind GPGR, and summarize current progress in the areas of the definition and construction of core collections, enhancement of germplasm with core collections, and gene discovery from core collections. GPGR is opening a new era in germplasm research. The contribution, progress and achievements of GPGR in the future are predicted.

  14. A Cross-Disciplinary Literature Review: Examining Trust on Virtual Teams

    Science.gov (United States)

    Berry, Gregory R.

    2011-01-01

    Effective and efficient teams communicate, collaborate, and perform, even if these teams are not co-located. Although much is known about enabling effectiveness on face-to-face teams, considerably less is known about similarly enabling effectiveness on virtual teams. Yet the use of virtual teams is common and will likely become more commonplace as…

  15. 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

    In Denmark we currently have an increased focus on preserving the most valuable domestic building examples from the period 1945 - 60. New literature deals with these architectural heritage matters. The authors of this paper argue, that due to question of preservation the buildings physiology is n...

  16. 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.

  17. 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.

  18. RHETORICAL PATTERNS, VERB TENSE, AND VOICE IN CROSS DISCIPLINARY RESEARCH ARTICLE ABSTRACT

    Directory of Open Access Journals (Sweden)

    Sharifah Hanidar

    2016-05-01

    Full Text Available This article investigates research article abstracts in terms of their rhetorical patterns and the use of verb tenses and voice. A total of 40 abstracts were selected from four international journals in the fields of Biology, Mechanical Engineering, Linguistics, and Medicine. A four move model was adopted from Hardjanto (1997 to analyze the structure of the abstracts. The results show that all the abstracts have Move 1, creating a research space; 70% have Move 2, describing research procedure; 85% have Move 3, summarizing principal results; and 85% have Move 4, evaluating results. All the abstracts in medicine have Moves 1, 2, 3 and 4, whereas the most common pattern in Biology is Moves 1, 3 and 4, in Mechanical Engineering Moves 1, 2 and 3, and in Linguistics Moves 1, 2 and 4. This seems to suggest that there is a disciplinary variation in the structuring of RA abstracts in the four disciplines under investigation. With regard to the use of verb tense and voice in each move, the present tense and past tense in the active voice and the past tense in the passive voice were the most frequently used tenses. The present tense in the active voice was frequently used in Moves 1 and 4, while the past tense in the active voice was commonly used in Move 3 and the past tense in the passive voice was frequently found in Move 2. Furthermore, it was found that the present tense in the active voice was frequently used in Biology, Mechanical Engineering and Linguistics, whereas the past tense in the active voice occurred more frequently in Medicine, and the past tense in the passive voice was more frequently found in Mechanical Engineering than in other disciplines.

  19. The History of the English Language Course: A Cross-Disciplinary Approach to the Humanities

    Science.gov (United States)

    Dressman, Michael R.

    2007-01-01

    The study of the history of the English language can help students become aware of major issues in several academic fields, including history, literature, political science, anthropology, communication, economics, the Arts, and, of course, languages and linguistics. Even though instructors may not have an especially broad background in the…

  20. Integrative studies of cultural evolution: crossing disciplinary boundaries to produce new insights.

    Science.gov (United States)

    Kolodny, Oren; Feldman, Marcus W; Creanza, Nicole

    2018-04-05

    Culture evolves according to dynamics on multiple temporal scales, from individuals' minute-by-minute behaviour to millennia of cultural accumulation that give rise to population-level differences. These dynamics act on a range of entities-including behavioural sequences, ideas and artefacts as well as individuals, populations and whole species-and involve mechanisms at multiple levels, from neurons in brains to inter-population interactions. Studying such complex phenomena requires an integration of perspectives from a diverse array of fields, as well as bridging gaps between traditionally disparate areas of study. In this article, which also serves as an introduction to the current special issue, we highlight some specific respects in which the study of cultural evolution has benefited and should continue to benefit from an integrative approach. We showcase a number of pioneering studies of cultural evolution that bring together numerous disciplines. These studies illustrate the value of perspectives from different fields for understanding cultural evolution, such as cognitive science and neuroanatomy, behavioural ecology, population dynamics, and evolutionary genetics. They also underscore the importance of understanding cultural processes when interpreting research about human genetics, neuroscience, behaviour and evolution.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'. © 2018 The Author(s).

  1. Cross-disciplinary management of polytrauma patients: radiological screening and comparison

    International Nuclear Information System (INIS)

    Messmer, P.; Loew, R.; Jacob, A.L.

    2001-01-01

    The comprehensive survey addresses the various modalities available today for trauma screening and presents a comparative assessment of their value in respect of type of trauma and evidence provided. (orig./CB) [de

  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. 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…

  4. 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.

  5. A staffing decision support methodology using a quality loss function : a cross-disciplinary quantitative study

    NARCIS (Netherlands)

    Mincsovics, G.Z.

    2009-01-01

    Background Understanding the quality loss implications of short staffing is essential in maintaining service quality on a limited budget. Objectives For elaborate financial control on staffing decisions, it is necessary to quantify the cost of the incidental quality loss that a given workload and

  6. 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…

  7. 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

  8. 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.

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

    OpenAIRE

    Karine Oganisjana; Tatjana Koke

    2012-01-01

    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 nurtur...

  10. 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…

  11. Workshop: Preventing Air Pollution-related Cardiopulmonary Illnesses: Innovative, Cross-disciplinary Solutions

    Science.gov (United States)

    On Sept. 28-29, 2016 in Washington, DC, EPA’s held its first workshop to share multi-stakeholder perspectives on how to improve cardiopulmonary health outcomes through the integration of environmental health, public health, health care services, data.

  12. 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

  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. Environmental law. A course of lectures for a cross-disciplinary audience

    International Nuclear Information System (INIS)

    Schulte, H.

    1999-01-01

    Readers interested in getting more insight in the legal framework available for supporting environmental protection policy will find a comprehensive picture of the environmental law applicable in Germany. The format chosen for the book is that of a lecture series, so that the reader is given step-by-step orientation and systematic guidance in approaching the complex material. The positive law and the underlying scientific systems are explained. An introductory part discusses the legal instruments available for enforcement of environmental law, the position of environmental law within the entire legal system of Germany, as well as relevant aspects of the law of the European Union, and international law. The subsequent chapters present an exhaustive survey of the subjects and objectives of German environmental law, as well as the legal practice and the issues involved. The chapters' headings read as follows: Abatement and control of emissions; the structure and functions of the state; administrative powers and action; civil rights and environmental protection; atomic energy law; water protection; waste management; nature conservation; the law on chemicals; the law relating to genetic engineering. The final chapter discusses aspects of environmental liability. (orig./CB) [de

  15. Post It!--A Cross-Disciplinary Approach to Teach Socioscientific Issues

    Science.gov (United States)

    Rundgren, Shu-Nu Chang

    2011-01-01

    Various socioscientific issues (SSIs) are emerging in today's science--and technology--dominant society, e.g. genetically modified organisms and global warming. To achieve the goal of scientific literacy, more and more science educators have devoted their attention to enhancing students' understanding of the multidimensional aspects of SSIs as…

  16. Outcomes of a Cross-Disciplinary Concussion Prevention and Diagnosis Workshop Series

    Directory of Open Access Journals (Sweden)

    Patrick Drane

    2018-02-01

    Full Text Available This paper reports the outcomes of a series of two Concussion Research Workshops held in Lowell, MA, USA. The workshop examined the state-of-the-art in concussion research, research challenges and the future directions of research within the following three core topic areas: (A Concussion Prevention Techniques & Technology, (B Concussion Diagnosis, and (C Treatment of Concussions. Concussions are a form of traumatic brain injury caused by an impact and are a growing concern among athletes and those who are involved with sports. Recent years have led to increasing awareness and research related to concussions with limited definitive understanding of the specific mechanism and pathology. Technology is beginning to take on an important role in the prevention, diagnosis and treatment of concussions. Currently, sensors provide data about the impact and the athlete. However, sensors and better protective equipment can enable an effective monitoring and thus protection of athletes. Only when a more definitive understanding of the injury mechanism is achieved, can sensors and protective equipment design contribute to effective monitoring and protection of athletes.

  17. Understanding Neurophobia: Reasons behind Impaired Understanding and Learning of Neuroanatomy in Cross-Disciplinary Healthcare Students

    Science.gov (United States)

    Javaid, Muhammad Asim; Chakraborty, Shelly; Cryan, John F.; Schellekens, Harriët; Toulouse, André

    2018-01-01

    Recent studies have highlighted a fear or difficulty with the study and understanding of neuroanatomy among medical and healthcare students. This has been linked with a diminished confidence of clinical practitioners and students to manage patients with neurological conditions. The underlying reasons for this difficulty have been queried among a…

  18. Beyond Deficit-filling and Developmental Stakes: Cross-disciplinary Perspectives on Parental Heritage.

    Science.gov (United States)

    Moss, Nancy E.; Abramowitz, Stephen I.

    1982-01-01

    Proposes an interdisciplinary conceptual foundation for studying parental heritage. Defines parental heritage as the intentional transmission of valued psychological and material assets from parent to child. Suggests advances in the realm of parental heritage are dependent on clarification of the complex interactions among such sociohistorical,…

  19. 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 ...

  20. Betavoltaic Battery Conversion Efficiency Improvement Based on Interlayer Structures

    International Nuclear Information System (INIS)

    Li Da-Rang; Jiang Lan; Yin Jian-Hua; Lin Nai; Tan Yuan-Yuan

    2012-01-01

    Significant differences among the doping densities of PN junctions in semiconductors cause lattice mismatch and lattice defects that increase the recombination current of betavoltaic batteries. This extensively decreases the open circuit voltage and the short current, which results in low conversion efficiency. This study proposes P + PINN + -structure based betavoltaic batteries by adding an interlayer to typical PIN structures to improve conversion efficiency. Numerical simulations are conducted for the energy deposition of beta particles along the thickness direction in semiconductors. Based on this, 63 Ni-radiation GaAs batteries with PIN and P + PINN + structures are designed and fabricated to experimentally verify the proposed design. It turns out that the conversion efficiency of the betavoltaic battery with the proposed P + PINN + structure is about 1.45 times higher than that with the traditional PIN structure. (cross-disciplinary physics and related areas of science and technology)

  1. 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.

  2. 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

  3. Zingiber officinale: Its antibacterial activity on Pseudomonas aeruginosa and mode of action evaluated by flow cytometry.

    Science.gov (United States)

    Chakotiya, Ankita Singh; Tanwar, Ankit; Narula, Alka; Sharma, Rakesh Kumar

    2017-06-01

    Biofilm formation, low membrane permeability and efflux activity developed by Pseudomonas aeruginosa, play an important role in the mechanism of infection and antimicrobial resistance. In the present study we evaluate the antibacterial effect of Zingiber officinale against multi-drug resistant strain of P. aeruginosa. The study explores antibacterial efficacy and time-kill study concomitantly the effect of herbal extract on bacterial cell physiology with the use of flow cytometry and inhibition of biofilm formation. Z. officinale was found to inhibit the growth of P. aeruginosa, significantly. A major decline in the Colony Forming Units was observed with 3 log 10  at 12 h of treatment. Also it is found to affect the membrane integrity of the pathogen, as 70.06 ± 2.009% cells were found to stain with Propidium iodide. In case of efflux activity 86.9 ± 2.08% cells were found in Ethidium bromide positive region. Biofilm formation inhibition ability was found in the range of 68.13 ± 4.11% to 84.86 ± 2.02%. Z.officinale is effective for killing Multi-Drug Resistant P. aeruginosa clinical isolate by affecting the cellular physiology and inhibiting the biofilm formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    1994-05-01

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

  5. Silage extracts used to study the mode of action of silage inoculants in ruminants

    Science.gov (United States)

    Silage microbial inoculants can enhance animal performance, but the mechanisms involved in these effects are not clear. Our hypothesis was that an extractable factor from inoculated silage enhances rumen microbial activity. One alfalfa haylage (58% DM) and two corn silages (30% and 50% DM) were made...

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

    NARCIS (Netherlands)

    Jager, D.T.; Crommentuijn, T.; van Gestel, C.A.M.; Kooijman, S.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

  7. 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.

  8. 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.

  9. Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation.

    Science.gov (United States)

    Mitrophanov, Alexander Y; Reifman, Jaques

    2011-10-01

    The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modulate thrombin production, it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about thrombin generation mechanisms. The existing body of knowledge about coagulation biochemistry can be rigorously represented by a computational model that incorporates the known reactions and parameter values constituting the biochemical network. We used a thoroughly validated numerical model to generate activated factor VII (FVIIa) titration curves in the cases of normal blood composition, hemophilia A and B blood, blood lacking factor VII, blood lacking tissue factor pathway inhibitor, and diluted blood. We utilized the generated curves to perform systematic fold-change analyses for five quantitative parameters characterizing thrombin accumulation. The largest fold changes induced by increasing FVIIa concentration were observed for clotting time, thrombin peak time, and maximum slope of the thrombin curve. By contrast, thrombin peak height was much less affected by FVIIa titrations, and the area under the thrombin curve stayed practically unchanged. Comparisons with experimental data demonstrated that the computationally derived patterns can be observed in vitro. rFVIIa modulates thrombin generation primarily by accelerating the process, without significantly affecting the total amount of generated thrombin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. 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

  11. ON THE MODE OF ACTION OF SULFANILAMIDE IN EXPERIMENTAL STREPTOCOCCUS EMPYEMA.

    Science.gov (United States)

    Gay, F P; Clark, A R

    1937-10-31

    Sulfanilamide prevents the evolution of an invariably fatal streptococcus empyema in rabbits when it is given repeatedly and in sufficient doses subcutaneously. Complete sterilization of the inoculated cavity occurs on approximately the 2nd day. The serum, defibrinated blood and artificial pleural exudate of similarly treated animals inhibits the growth of the same streptococcus in the test tube but even repeated doses of such treated blood serum fail to sterilize the culture. The coccal chains grown in such drugged serum are elongated and present pleomorphic and metachromatic organisms and may give rise to colonies that are at first less predominantly mucoid in appearance. Such organisms have, however, lost little if any of their virulence. Cooperation on the part of locally derived clasmatocytes is apparently required in complete sterilization of the animal body. This conclusion is reached not only by a process of exclusion from comparison with the test tube results, but through the direct histological demonstration of a precocious and increasing mobilization of clasmatocytes in the parietal and visceral pleura of treated animals. In other words, sulfanilamide apparently produces a bacteriostasis sufficiently marked to protect the accumulated leucocytes and to allow the natural defense macrophages to accumulate. There is direct evidence that the drug does not in itself stimulate the mobilization of the macrophages. There is no evidence that the cell reaction which finally accounts for disposal of the organisms is other than local.

  12. 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.

    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

  13. PA01.33. Mode of action of medhya drugs: A review

    OpenAIRE

    Mehra, Bhawana; Dwivedi, K. N.

    2012-01-01

    Purpose: Memory is combination of power of acquisition (Grahan), retention (Dharan) and recollection (Smaran). Vata, pitta, and kapha are the three psychobiological dimensions (energy) or biological rhythms regulating the entire functioning of the human body. Pitta is responsible for understanding and attaining knowledge due to its Satva, Aashukari and Tikshna property. Vata is responsible for association of ideas. Kapha provides stability which is necessary for retention of memory. Several C...

  14. Mode of action of Bacillus licheniformis pectin methylesterase on highly methylesterified and acetylated pectins

    NARCIS (Netherlands)

    Remoroza, C.A.; Wagenknecht, M.; Buchholt, H.C.; Moerschbacher, B.M.; Gruppen, H.; Schols, H.A.

    2015-01-01

    A gene encoding a putative pectinesterase from Bacillus licheniformis DSM13 was cloned and expressed in Escherichia coli. The resulting recombinant enzyme (BliPME) was purified and characterized as a pectin methylesterase. The enzyme showed maximum activity at pH 8.0 and 50 °C. BliPME is able to

  15. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses

    Directory of Open Access Journals (Sweden)

    Lyubomir A. Dourmishev

    2016-01-01

    Full Text Available Intravenous immunoglobulins (IVIGs, a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies, as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.

  16. 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...

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

    Science.gov (United States)

    2012-01-01

    Ostrinia nubilalis. PLoS ONE 5, e8685. Wanner, K.W., Nichols, A.S.,Walden, K.K., Brockmann, A., Luetje, C.W., Robertson, H.M., 2007. A honey bee odorant...allosteric”. Protein Sci. 20, 1119e1124. Christopoulos, A., Kenakin, T., 2002. G protein -coupled receptor allosterism and complexing. Pharmacol. Rev. 54...Newcomb, R.D., Warr, C.G., 2008. Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of

  18. Mode of Action of Shigella Toxin: Effects on Ribosome Structure and Function

    Science.gov (United States)

    1988-05-01

    1974. Sindrome hemolitico uremico: reporte de 60 casos asociados a una epidemia de enterocolitis hemorragica. Revista Colombiana de Ped. Puericult. 28...1518-1521. 34. Fong, J.S.C., J-P de Chadarevian and B.S. Kaplan. 1982. Hemolytic-uremic syndrome: current concepts and management. Ped. Clin. North Am

  19. MODE OF ACTION: INHIBITION OF ANDROGEN RECEPTOR FUNCTION--VINCLOZOLIN-INDUCED MALFORMATIONS IN REPRODUCTIVE DEVELOPMENT

    Science.gov (United States)

    Vinclozolin is a fungicide that has been shown to cause Leydig cell tumors and atrophy of the accessory sex glands in adult rodents. In addition, exposure of rats during pregnancy causes a pattern of malformations in the male urogenital tract. A wealth of standard toxicological s...

  20. Curcumin and Chronic Kidney Disease (CKD: Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

    Directory of Open Access Journals (Sweden)

    Siddhartha S. Ghosh

    2014-12-01

    Full Text Available Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa, has significant anti-inflammatory properties. Chronic kidney disease (CKD, an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP. Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.

  1. Mode of Action Frameworks in Toxicity Testing and Chemical Risk Assessment

    NARCIS (Netherlands)

    Meek, B.

    2009-01-01

    Recently, legislative mandates worldwide are requiring systematic consideration of much larger numbers of chemicals. This necessitates more efficient and effective toxicity testing, as a basis to be more predictive in a risk assessment context. This in turn requires much more emphasis early in the

  2. Identification, purification and elucidation of the mode of action of (novel) antimicrobial substances

    NARCIS (Netherlands)

    Oppedijk, S.F.

    2017-01-01

    Antibiotics are among the most frequently prescribed medications in current medicine, however there is an increasing resistance emerging against our current arsenal of antibiotics. Therefore, it is important that we do research into antimicrobial substances that uniquely work on essential pathways

  3. The Cyclic Antibacterial Peptide Enterocin AS-48: Isolation, Mode of Action, and Possible Food Applications

    OpenAIRE

    Grande Burgos, Mar?a Jos?; P?rez Pulido, Rub?n; L?pez Aguayo, Mar?a del Carmen; G?lvez, Antonio; Lucas, Rosario

    2014-01-01

    Enterocin AS-48 is a circular bacteriocin produced by Enterococcus. It contains a 70 amino acid-residue chain circularized by a head-to-tail peptide bond. The conformation of enterocin AS-48 is arranged into five alpha-helices with a compact globular structure. Enterocin AS-48 has a wide inhibitory spectrum on Gram-positive bacteria. Sensitivity of Gram-negative bacteria increases in combination with outer-membrane permeabilizing treatments. Eukaryotic cells are bacteriocin-resistant. This ...

  4. Modes of Action of 3-Amino-1, 2, 4-Triazole: Current Status

    Energy Technology Data Exchange (ETDEWEB)

    Hilton, J. L. [United States Department of Agriculture, Belts Ville, MD (United States)

    1966-05-15

    3-amino-1, 2, 4-triazole (amitrole) is a selective herbicide toxic to many species of green plants and micro-organisms. The primary biochemical site of action does not appear to be the same in all organisms. Growth inhibitions are reversed by purines or, more effectively, by histidine in micro-organisms or by riboflavin in green plants. Both metabolites are products derived from purine metabolism. Therefore, a study of amitrole effects on purine metabolism in various organisms is in progress. Saccharomyces cerevisiae Meyen ex Hansen is highly sensitive to amitrole but may be protected by histidine. Amitrole inhibits incorporation of {sup 14}C from adenine-2- {sup 14}C into proteins and nucleic acids, and causes imidazoleglycerol phosphate-4C (IGP- {sup 14}C) to accumulate as a result of competitive inhibition of IGP dehydratase, one of the enzymes of the histidine biosynthetic pathway. Amitrole affinity for the enzyme is approximately 10 times that of IGP. The inhibition releases the histidine pathway from feedback control thereby permitting IGP to accumulate at the expense of the purine pool. The concept of an induced purine deficiency provides interpretation for the observation that: (a) purines provide limited protection against amitrole; (b) an inhibitor of adenine biosynthesis offers protection comparable to that of purines; and (c) that inhibition of riboflavin biosynthesis in Eremothecium ashbyii Guill. is reversed by histidine. Riboflavin protection of green plants against amitrole results primarily from chemical inactivation of amitrole by photoactivated flavins; however, some support for a physiological mechanism of protection still exists. Bacteria are approximately 1/100-th as sensitive to amitrole as yeasts. Biosynthesis of IGP dehydratase is derepressed in amitrole-treated Salmonella typhimurium (Loeffler) Cast, and Chalm. As a result of the increased enzyme level, higher concentrations of amitrole are required to affect growth. At these high concentrations histidine alone will protect growth temporarily. Continued reversal of amitrole toxicity requires a combination of histidine and adenine. Therefore, interference with an enzyme of purine metabolism is suspected. Amitrole does affect utilization of glycine-1-{sup 14}C for purine metabolism. The nature of the effect is under investigation. Inhibition of histidine biosynthesis appears to be a major mechanism of amitrole action in yeast, bacteria, fungi, and algae. However, efforts to obtain evidence for this mechanism in higher plants have been inconclusive. Herbicidal activity probably involves numerous sites of action, some of which might not be detected in micro-organisms. (author)

  5. Screening of Various Herbicide Modes of Action for Selective Control of Algae Responsible for Harmful Blooms

    Science.gov (United States)

    2009-01-01

    included, Scenedesmus quadricauda and Selenastrum sp. After a two-week exposure period, all flasks were filtered. The planktonic algae were measured...activity against the various algal species tested (Figures 1 through 7). Aside from the reduction in biomass of the green alga Scenedesmus by...controls (Figures 1 through 7). Penoxsulam was highly active against the blue-greens Cylindrospermopsis and Anabaena, and the green alga Scenedesmus

  6. Riboflavin analogs as antiinfectives: occurrence, mode of action, metabolism and resistance.

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Jankowitsch, Frank; Schwarz, Julia; Langer, Simone; Nakanishi, Shinobu; Frei, Eva; Mack, Matthias

    2013-01-01

    Antimetabolites are molecules, which are structurally similar to molecules needed to carry out primary metabolic reactions.The inhibitory activity of an antimetabolite depends on its successful competition with the natural substrate, ligand, modulator or cofactor of a given biomolecule. Antimetabolites are indispensable as molecular tools in order to understand biological processes. Beyond that,antimetabolites have a large variety of applications in the pharmaceutical and food industries. The identification of the structural riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates that anti-vitamins/cofactor analogs may serve as lead structures for the development of novel antibiotics. The latter is supported by the recent finding that roseoflavin had a profound inhibiting effect on the growth and infectivity of the human bacterial pathogen Listeria monocytogenes at very low concentrations. Roseoflavin is studied in our laboratory as a model compound. We investigate the biosynthesis, the possible large-scale production, the metabolization,the mechanism of action and the resistance mechanism of the producer organism in order to pave the way for the structured analysis of other vitamin analogs yet to be discovered. These compounds hopefully will help to replenish the arsenal of antimicrobials urgently needed to fight multiresistant bacterial pathogens.

  7. 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.

  8. 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...

  9. A fast kinetics study of the modes of action of some different radiosensitizers in bacteria

    International Nuclear Information System (INIS)

    Michael, B.D.; Harrop, H.A.; Maughan, R.L.; Patel, K.B.

    1978-01-01

    Using a fast mixing and irradiation technique, the gas explosion method, with Serratia marcescens, the decay of oxygen-dependent damage is found to consist of a fast and a slow stage, each of which is associated with a subcomponent of this damage. In the present work, the interactions of these components with radiosensitizers are examined. At low concentrations, O 2 , TAN (a nitroxyl) and misonidazole all preferentially sensitize the slow-stage damage. At higher concentrations, O 2 and TAN sensitize the fast-stage damage by a fixation reaction that competes with its repair; in contrast, misonidazole appears mainly to operate by reaction with an earlier, even shorter lived form of oxygen-dependent damage. (author)

  10. Proceedings of the 2006 Toxicology and Risk Assessment Conference: Applying Mode of Action in Risk Assessment

    Science.gov (United States)

    2006-07-01

    Biomonitoring Studies to Assess Exposure and Risk of Inorganic Arsenic: Confounding by Other Sources of Arsenic Beck , Barbara D., Ph.D., D.A.B.T., Gradient... Beck , Barbara D.; Schoen, Ari Gradient Corporation Arsenic can exist in the environment in a number of different forms, each form with its own...equipped with a mass selective detector (MSD) using a dimethylpolysiloxane (HP-1) capillary column. Deuterated 2-butoxyacetic acid (d- BAA ) was

  11. 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

  12. 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

  13. [Mode of action of plantaricin L-1, an antilisteria bacteriocin produced by Lactobacillus plantarum].

    Science.gov (United States)

    Zhou, Wei; Liu, Guo-rong; Li, Ping-lan; Dai, Yun-qing; Zhou, Kang

    2007-04-01

    Plantaricin L-1, an anti-Listeria bacteriocin, was produced by Lactobacillus plantarum and successfully purified by SP-Sepharose FF cation exchange chromatography. The mechanism on energized cells of Listeria monocytogenes was studied with purified plantaricin L-1. After adding plantaricin L-1 to Listeria monocytogenes at 64 AU/mL, leakage of intercellular K+ ions, inorganic phosphate, lactic dehydrogenase, UV-absorbing materials and the intracellular ATP was observed, and the action resulted in the dissipation of the membrane potential (delta psi) and pH gradient (delta psi), two components of the proton motive force (PMF). All the data suggested that the primary site of action of plantaricin L-1 was the cytoplasmic membrane of sensitive cells. By forming the nonselective pores which leak ions and small organic compounds plantaricin L-1 induced the cells death, this action was similar to membrane corruption caused by peptide effect. Penetrability increased due to the enlarged pore and dysfuction of membrane transporters, which ensured efficient killing of target bacteria.

  14. Etiology of bromate-induced cancer and possible modes of action-studies in Japan

    International Nuclear Information System (INIS)

    Umemura, Takashi; Kurokawa, Yuji

    2006-01-01

    Renal cell tumors were significantly increased in male and female rats given potassium bromate at 250 and 500 mg/L in drinking water. In at least one other study renal cell tumors were produced in male rats at 125 mg/L. Among male mice given 750 mg/L of potassium bromate, there were no significant differences in renal cell tumors between treated and control groups after 88 weeks on test. In oxidative DNA damage tests 8-oxodeoxyguanosine (8-oxodG also referred to as 8-OH-dG) was induced in DNA in the male rat kidney in 1 week, and in females after 3 weeks at 500 mg/L, and also in both male and female rats at 250 mg/L, but not at 125 mg/L. DNA adducts are considered to be an initial step in the carcinogenesis process, however, the administered doses are not always sufficient to cause mutations, possibly due to DNA repair. In the two-step rat renal carcinogenesis model using N-ethyl-N-hydroxyethylnitrosamine (EHEN) as initiator, promotion activity by potassium bromate was measured using the BrdU labeling index. The promoting activity of bromate in male rats was much greater and extended to doses as low as 60 mg/L in male rats, whereas in females the response was limited to 250 and 500 mg/L. Therefore, it was concluded that the mechanisms contributing to cancer in the male rat were more complex than in the female rat. The accumulation of α 2μ -globulin in the kidneys of male rats exposed to potassium bromate probably accounts for the greater labeling index in the male rat relative to the female rat. Accumulation of α 2μ -globulin as a result of treatment with chemicals is unique to the male rat and does contribute to carcinogenic responses. Neither humans nor female rats display this response. Nevertheless, bromate must be considered carcinogenic because of the response of the female rats. The better correlation between 8-oxodG formation and tumor response indicates that dose-response information from the female rat would be much more relevant to human risk assessment. The fact that an elevation of BrdU-LI in the kidney of the female rat is consistent with the possibility that cell proliferation observed in female rats resulted from oxidative stress and/or cytotoxic responses in the kidney. Therefore, oxidative stress is most likely the mechanism of interest for cancer risk in humans

  15. Natural product mode of action (MOA) studies: a link between natural and synthetic worlds.

    Science.gov (United States)

    La Clair, James J

    2010-07-01

    In our understanding of matter, natural products deliver plots that would stun even the best productions of the legendary filmmaker, Sergio Leone. While every decade heralds a new genre of film (as well as avenues of small-molecule discovery), natural products and their "untamed prehistoric" plots continue to dazzle the fields of biotechnology, drug discovery, fragrances, food additives and agrochemistry. This review provides an abridged synopsis of the modes of natural product action discovered within the last decade and the tools and methods used in their discovery. Their stories are united in a common theme that unveils one of the more vital aspects of chemical biological research:understanding the global activity of Nature's arsenal of secondary metabolites.

  16. The cellulases of Trichoderma viride : mode of action and application in biomass conversion

    NARCIS (Netherlands)

    Beldman, G.

    1986-01-01

    Beet pulp and potato fibre were liquefied and saccharified with a combination of cellulase from Trichodermaviride and pectinase from Aspergillusniger . Cell wall polysaccharides were hydrolysed extensively. The application

  17. 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

  18. 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.

  19. Antimicrobial compounds targeting Gram-negative bacteria in food: Their mode of action and combinational effects

    DEFF Research Database (Denmark)

    Hyldgaard, Morten

    2015-01-01

    compromising food shelf-life or safety. Natural antimicrobial compounds have therefore gained increased interest as a label-friendly alternative that can be added directly to food products. Although natural antimicrobials constitute an interesting source of compounds, it is often not understood how...... 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...

  20. New concepts in antimalarial use and mode of action in dermatology.

    Science.gov (United States)

    Kalia, Sunil; Dutz, Jan P

    2007-01-01

    Although chloroquine, hydroxychloroquine and quinacrine were originally developed for the treatment of malaria, these medications have been used to treat skin disease for over 50 years. Recent clinical data have confirmed the usefulness of these medications for the treatment of lupus erythematosus. Current research has further enhanced our understanding of the pharmacologic mechanisms of action of these drugs involving inhibition of endosomal toll-like receptor (TLR) signaling limiting B cell and dendritic cell activation. With this understanding, the use of these medications in dermatology is broadening. This article highlights the different antimalarials used within dermatology through their pharmacologic properties and mechanism of action, as well as indicating their clinical uses. In addition, contraindications, adverse effects, and possible drug interactions of antimalarials are reviewed.

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

    African Journals Online (AJOL)

    HP

    1College of Life Science and Bioengineering, Beijing University of ... association between cochinchinenin B and TTX-R sodium channel were ..... Data were expressed as the mean ± SEM. .... Thus at the beginning of the reaction, the drugs.

  2. Cold atmospheric-pressure plasma and bacteria: understanding the mode of action using vibrational microspectroscopy

    International Nuclear Information System (INIS)

    Kartaschew, Konstantin; Mischo, Meike; Bründermann, Erik; Havenith, Martina; Baldus, Sabrina; Awakowicz, Peter

    2016-01-01

    Cold atmospheric-pressure plasma show promising antimicrobial effects, however the detailed biochemical mechanism of the bacterial inactivation is still unknown. We investigated, for the first time, plasma-treated Gram-positive Bacillus subtilis and Gram-negative Escherichia coli bacteria with Raman and infrared microspectroscopy. A dielectric barrier discharge was used as a plasma source. We were able to detect several plasma-induced chemical modifications, which suggest a pronounced oxidative effect on the cell envelope, cellular proteins and nucleotides as well as a generation of organic nitrates in the treated bacteria. Vibrational microspectroscopy is used as a comprehensive and a powerful tool for the analysis of plasma interactions with whole organisms such as bacteria. Analysis of reaction kinetics of chemical modifications allow a time-dependent insight into the plasma-mediated impact. Investigating possible synergistic effects between the plasma-produced components, our observations strongly indicate that the detected plasma-mediated chemical alterations can be mainly explained by the particle effect of the generated reactive species. By changing the polarity of the applied voltage pulse, and hence the propagation mechanisms of streamers, no significant effect on the spectral results could be detected. This method allows the analysis of the individual impact of each plasma constituent for particular chemical modifications. Our approach shows great potential to contribute to a better understanding of plasma-cell interactions. (paper)

  3. 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

  4. 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

  5. Mode of action of xylogalacturonan hydrolase towards xylogalacturonan and xylogalacturonan oligosaccharides

    Science.gov (United States)

    2004-01-01

    XGH (xylogalacturonan hydrolase; GH 28) is an enzyme that is capable of degrading XGA (xylogalacturonan), which is a polymer of α-D-galacturonic acid, highly substituted with β-D-xylose. XGA is present in cell walls of various plants and exudates, such as gum tragacanth. XGA oligosaccharides were derived from an XGH digestion of gum tragacanth, then fractionated, and analysed for their sugar composition and structure by matrix-assisted laser-desorption ionization–time-of-flight MS and nanospray MS. Several oligosaccharides from XGA were identified with different galacturonic acid/xylose ratios including five oligosaccharide isomers. Although XGH can act as an endo-enzyme, product-progression profiling showed that the disaccharide GalAXyl was predominantly produced from XGA by XGH, which indicated also an exolytic action. The latter was further supported by degradation studies of purified oligosaccharide GalA4Xyl3. It was shown that XGH acted from the non-reducing end towards the reducing end of this oligosaccharide, and showed the processive character of XGH. The results from this study further show that although XGH prefers to act between two xylosidated GalA units, it tolerates unsubstituted GalA units in its −1 and +1 subsites. PMID:15560751

  6. 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

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

    OpenAIRE

    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.

    2014-01-01

    Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicoti...

  8. The combined mode of action of fipronil and amitraz on the motility of Rhipicephalus sanguineus.

    Science.gov (United States)

    Prullage, Joseph B; Tran, Hai V; Timmons, Phil; Harriman, Jay; Chester, S Theodore; Powell, Kerrie

    2011-07-15

    The motility of adult Rhipicephalus sanguineus was evaluated subsequent to treatments of amitraz, fipronil and the combination of fipronil plus amitraz against a vehicle control in a Petri dish assay using the LemnaTec Scanalyzer Imaging System. The assay was run using a fixed dilution of amitraz (0.32μg/cm(2)); serial dilutions of fipronil (1.3, 0.33, 0.08, 0.02, or 0.005μg/cm(2)); and the same serial dilutions of fipronil in combination with the fixed dilution of amitraz. Measurement of motility was made of unstimulated ticks and then after stimulation at 1, 4, 18-22, and 24h post exposure (hpe) of the Petri dishes. For the unstimulated ticks, there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. However, these two treatment groups had significantly higher motility than the solvent control and fipronil treatment groups. The unstimulated ticks in the amitraz treatment group had significantly higher motility than the fipronil plus amitraz treatment group at the later time points. Measurements after stimulation demonstrated there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. By 18 hpe, the fipronil plus amitraz treatment group had significantly lower motility than all other treatment groups and at 21-22 and 24 hpe the other treatment groups did not differ from the control group. The action could be divided in two phases in the combination experiment: phase 1: an early increase in motility due to amitraz is identified in both amitraz alone or fipronil plus amitraz groups; phase 2: the combination of fipronil plus amitraz caused a significantly greater reduction in motility, suggesting mortality of the ticks, compared to fipronil or amitraz alone. These results demonstrate a synergism resulting from the combination of fipronil plus amitraz. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Metabolic products of microorganisms. 184. On the mode of action of cladosporin.

    Science.gov (United States)

    Anke, H

    1979-09-01

    Cladosporin, a fungal isocoumarin derivative, strongly inhibits the uptake and thereby the incorporation of uracil and leucine into cells of Bacillus brevis and the incorporation of uridine but not leucine into cells of the ascitic form of Ehrlich carcinoma (ECA) of mice. Normal uptake was not restored by removal of the antibiotic. In cells of Escherichia coli A 19-15 (met-) the inhibition of methionine uptake is associated with the cessation of growth. In a methionine-prototrophic revertant from this organism, the uptake of methionine is still inhibited; growth, however, is hardly affected by cladosporin. In vitro no effect on the DNA-dependent RNA polymerase from E. coli and on the RNA polymerase II from wheat germ could be detected. The poly(U)-directed poly(Phe) synthesis was also not inhibited by cladosporin. It is concluded that cladosporin inhibits uptake processes which, for the case of essential nutrients, leads to loss of viability.

  10. Characterization and mode of action of xylanases ␁and some accessory enzymes

    NARCIS (Netherlands)

    Kormelink, F.J.M.

    1992-01-01

    Three endo-(l,4)-β-D-xylanases; (Endo I, Endo II, and Endo III), a (1,4)-β-xylosidase and an (1,4)-β-D-arabinoxylan arabinofuranohydrolase (AXH) were purified from a culture filtrate produced by Aspergillus awamori CMI 142717. In addition to these enzymes, an acetyl

  11. 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

    Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N'-(2-(4'-methylmorpholinio)ethyl)N"-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 microgram/ml...

  12. Bioefficacy and mode-of-action of some limonoids of salannin group ...

    Indian Academy of Sciences (India)

    Unknown

    ... Nucleosil C-18 RP. The mobile phase was .... 100] and approximate digestibility (AD) as [(food ingested – .... Table 1. Effective concentrations (ppm) of various salannin type limonoids inhibiting growth (neonates) of H. armigera and S. litura.

  13. Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.

    Science.gov (United States)

    Findeisen, Maria; Würker, Cäcilia; Rathmann, Daniel; Meier, René; Meiler, Jens; Olsson, Roger; Beck-Sickinger, Annette G

    2012-07-12

    The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By use of four nonpeptidic compounds and the peptide mimetics RF9 and BIBP3226, agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated. The binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of AC-216 interacts with position 7.35 in the NPFF(1) but not in the NPFF(2) receptor. These results provide distinct insights into the receptor specific binding pockets, which is necessary for the development of drugs to address the NPFF system.

  14. Membrane Transport Inhibition as Mode of Action of Polyene Antimycotics: Recent Data Supported by Old Ones

    Czech Academy of Sciences Publication Activity Database

    Opekarová, Miroslava; Tanner, W.

    2014-01-01

    Roč. 52, č. 1 (2014), s. 8-12 ISSN 1330-9862 R&D Projects: GA ČR GAP305/12/0480 Institutional research plan: CEZ:AV0Z50200510 Keywords : amphotericin B * nystatin * natamycin Subject RIV: EE - Microbiology, Virology Impact factor: 0.920, year: 2014

  15. Highly Selective Phosphatidylinositol 4-Kinase III beta Inhibitors and Structural Insight into Their Mode of Action

    Czech Academy of Sciences Publication Activity Database

    Mejdrová, Ivana; Chalupská, Dominika; Kögler, Martin; Šála, Michal; Plačková, Pavla; Bäumlová, Adriana; Hřebabecký, Hubert; Procházková, Eliška; Dejmek, Milan; Guillon, Rémi; Strunin, Dmytro; Weber, Jan; Lee, G.; Birkuš, G.; Mertlíková-Kaiserová, Helena; Bouřa, Evžen; Nencka, Radim

    2015-01-01

    Roč. 58, č. 9 (2015), s. 3767-3793 ISSN 0022-2623 R&D Projects: GA MŠk LO1302; GA ČR GA15-09310S; GA ČR GJ15-21030Y EU Projects: European Commission(XE) 333916 - STARPI4K Institutional support: RVO:61388963 Keywords : phosphatidylinositol 4-kinase III beta * broad-spectrum antiviral agents * positive-sense RNA viruses Subject RIV: CC - Organic Chemistry Impact factor: 5.589, year: 2015

  16. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  17. Learning and Motivational Processes When Students Design Curriculum-Based Digital Learning Games

    DEFF Research Database (Denmark)

    Weitze, Charlotte Lærke

    2015-01-01

    This design-based research (DBR) project has developed an overall gamified learning design (big Game) to facilitate the learning process for adult students by inviting them to be their own learning designers through designing digital learning games (small games) in cross-disciplinary subject...... matters. The DBR project has investigated and experimented with which elements, methods, and processes are important when aiming at creating a cognitive complex (Anderson and Krathwohl, 2001) and motivating learning process within a reusable game-based learning design. This project took place in a co......, or programming provide a rich context for learning, since the construction of artefacts, in this case learning games, enables reflection and new ways of thinking. The students learned from reflection and interaction with the tools alone as well as in collaboration with peers. After analysing the students...

  18. Challenges and Strategies in Providing Home Based Primary Care for Refugees in the US.

    Science.gov (United States)

    Febles, C; Nies, M A; Fanning, K; Tavernier, S S

    2017-12-01

    The recent crisis in the Middle East has prompted the exodus of millions of refugees from the region who are at present seeking shelter across Europe and in the United States. Among the most immediate needs of refugees upon arrival in a host country is health care, and it is one of the most sustained interactions they experience. Home visits are a common form of primary care for refugees. The authors review the literature to identify themes related to challenges and strategies for providing home based primary care to refugees. The literature review was performed by searching cross-disciplinary databases utilizing Onesearch, but focusing primarily on results produced through CINAHL, EBSCOHOST, and Pub Med databases. To maximize the number of studies included, there was no time frame placed upon publication dates of articles within the search. A total of 55 articles were included in this paper.

  19. Effect of Interface Nanotexture on Light Extraction of InGaN-Based Green Light Emitting Diodes

    International Nuclear Information System (INIS)

    Yao-Bo, Pan; Sheng-Li, Qi; Hao, Fang; Guo-Yi, Zhang; Mao-Sheng, Hao

    2010-01-01

    We report the enhancement of the light extraction of InGaN-based green light emitting diodes (LEDs) via the interface nanotexturing. The texture consists of high-density nanocraters on the surface of a sapphire substrate with an in situ etching. The width of nanocraters is about 0.5 μm and the depth is around 0.1 μm. It is demonstrated that the LEDs with interface texture exhibit about a 27% improvement in luminance intensity, compared with standard LEDs. High power InGaN-based green LEDs are obtained by using the interface nanotexture. An optical ray-tracing simulation is performed to investigate the effect of interface nanotexture on light extraction. (cross-disciplinary physics and related areas of science and technology)

  20. Developing a leadership laboratory for nurse managers based on lived experiences: a participatory action research model for leadership development.

    Science.gov (United States)

    Mackoff, Barbara L; Glassman, Kimberly; Budin, Wendy

    2013-09-01

    The aim of the pilot study was to design an innovative model of leadership development, Leadership Laboratory (LL), grounded in the lived experiences and peer best practices of 43 cross-disciplinary nurse managers. The Institute of Medicine/Robert Wood Johnson Foundation study, The Future of Nursing, reinforces the need to prepare nurses for leadership positions. A 1-year participatory action research study was designed to develop 3 LLs involving nurse managers as participants, co-creators, and evaluators of the unique learning format. Analysis of qualitative and quantitative data revealed consistent and significantly positive results in leadership skill areas in all 3 LLs. Participants identified elements that distinguished LLs from traditional seminars and trainings sessions, including opportunities to gain from peer-to peer consultation, strategies, and support. Participants in the 1-year pilot demonstrated significant learning based on postsession and postproject assessments of the LLs. Data also described the unique attributes of a peer-driven approach to leadership development.

  1. Collaborative Management of Complex Major Construction Projects: AnyLogic-Based Simulation Modelling

    Directory of Open Access Journals (Sweden)

    Na Zhao

    2016-01-01

    Full Text Available Complex supply chain system collaborative management of major construction projects effectively integrates the different participants in the construction project. This paper establishes a simulation model based on AnyLogic to reveal the collaborative elements in the complex supply chain management system and the modes of action as well as the transmission problems of the intent information. Thus it is promoting the participants to become an organism with coordinated development and coevolution. This study can help improve the efficiency and management of the complex system of major construction projects.

  2. Toxin-Based Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Itai Benhar

    2010-10-01

    Full Text Available Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

  3. Toxin-Based Therapeutic Approaches

    Science.gov (United States)

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  4. High-Performance 1.55-µm Superluminescent Diode Based on Broad Gain InAs/InGaAlAs/InP Quantum Dash Active Region

    KAUST Repository

    Khan, Mohammed Zahed Mustafa

    2014-08-01

    We report on the high-performance characteristics from superluminescent diodes (SLDs) based on four-stack InAs/InGaAlAs chirped-barrier thickness quantum dash (Qdash) in a well structure. The active region exhibits a measured broad gain spectrum of 140 nm, with a peak modal gain of ~41 cm-1. The noncoated two-section gainabsorber broad-area and ridge-waveguide device configuration exhibits an output power of > 20 mW and > 12 mW, respectively. The corresponding -3-dB bandwidths span ~82 nm and ~72 nm, with a small spectral ripple of <; 0.2 dB, related largely to the contribution from dispersive height dash ensembles of the highly inhomogeneous active region. These C-L communication band devices will find applications in various cross-disciplinary fields of optical metrology, optical coherent tomography, etc.

  5. NSCT BASED LOCAL ENHANCEMENT FOR ACTIVE CONTOUR BASED IMAGE SEGMENTATION APPLICATION

    Directory of Open Access Journals (Sweden)

    Hiren Mewada

    2010-08-01

    Full Text Available Because of cross-disciplinary nature, Active Contour modeling techniques have been utilized extensively for the image segmentation. In traditional active contour based segmentation techniques based on level set methods, the energy functions are defined based on the intensity gradient. This makes them highly sensitive to the situation where the underlying image content is characterized by image nonhomogeneities due to illumination and contrast condition. This is the most difficult problem to make them as fully automatic image segmentation techniques. This paper introduces one of the approaches based on image enhancement to this problem. The enhanced image is obtained using NonSubsampled Contourlet Transform, which improves the edges strengths in the direction where the illumination is not proper and then active contour model based on level set technique is utilized to segment the object. Experiment results demonstrate that proposed method can be utilized along with existing active contour model based segmentation method under situation characterized by intensity non-homogeneity to make them fully automatic.

  6. Engineered chitosan based nanomaterials: Bioactivities, mechanisms and perspectives in plant protection and growth.

    Science.gov (United States)

    Kumaraswamy, R V; Kumari, Sarita; Choudhary, Ram Chandra; Pal, Ajay; Raliya, Ramesh; Biswas, Pratim; Saharan, Vinod

    2018-07-01

    Excessive use of agrochemicals for enhancing crop production and its protection posed environmental and health concern. Integration of advanced technology is required to realize the concept of precision agriculture by minimizing the input of pesticides and fertilizers per unit while improving the crop productivity. Notably, chitosan based biodegradable nanomaterials (NMs) including nanoparticles, nanogels and nanocomposites have eventually proceeded as a key choice in agriculture due to their inimitable properties like antimicrobial and plant growth promoting activities. The foreseeable role of chitosan based NMs in plants might be in achieving sustainable plant growth through boosting the intrinsic potential of plants. In-spite of the fact that chitosan based NMs abode immense biological activities in plants, these materials have not yet been widely adopted in agriculture due to poor understanding of their bioactivity and modes of action towards pathogenic microbes and in plant protection and growth. To expedite the anticipated claims of chitosan based NMs, it is imperative to line up all the possible bioactivities which denote for sustainable agriculture. Herein, we have highlighted, in-depth, various chitosan based NMs which have been used in plant growth and protection mainly against fungi, bacteria and viruses and have also explained their modes of action. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Science and Theatre Education: A Cross-Disciplinary Approach of Scientific Ideas Addressed to Student Teachers of Early Childhood Education

    Science.gov (United States)

    Tselfes, Vasilis; Paroussi, Antigoni

    2009-01-01

    There is, in Greece, an ongoing attempt to breach the boundaries established between the different teaching-learning subjects of compulsory education. In this context, we are interested in exploring to what degree the teaching and learning of ideas from the sciences' "internal life" (Hacking, in: Pickering (ed) "Science as practice…

  8. Variations in Textualization: A Cross-Generic and Cross-Disciplinary Study, Implications for Readability of the Academic Discourse

    Science.gov (United States)

    Bonabi, Mina Abbasi; Lotfipour-Saedi, Kazem; Hemmati, Fatemeh; Jafarigohar, Manoochehr

    2018-01-01

    According to discoursal views on language, variations in textualization strategies are always sociocontextually motivated and never happen at random. The textual forms employed in a text, along with many other discoursal and contextual factors, could certainly affect the readability of the text, making it more or less processable for the same…

  9. A cross-disciplinary assessment of student loans debt, financial support for study and career preferences upon graduation.

    Science.gov (United States)

    Webster, Craig S; Ling, Christopher; Barrow, Mark; Poole, Phillippa; Henning, Marcus

    2017-07-21

    To explore relationships between student loans debt, financial support and career preferences upon graduation for all healthcare disciplines offered at the Faculty of Medical and Health Sciences, University of Auckland. The Faculty Tracking Project is a longitudinal study which invites students to complete a questionnaire at the beginning and end of their educational programmes, including questions on debt, financial support and career preference. Our analysis comprised three phases: (1) a descriptive analysis of data related to debt and financial support; (2) a principal component analysis in order to find related categories of career choice; and (3) logistic regression models to determine how career preference categories could be explained by either levels of student loans debt or financial support. Data from 2,405 participating students were included. Students in health sciences, nursing and pharmacy typically accrue levels of student loans debt of around $15,000 to $29,999, while optometry students accrue debt around $15,000 higher. Medical students show debt distributed around modes of $0 and $90,000 or more. All students typically access three sources of financial support during study. Career preferences at graduation reduced to four categories for all health disciplines. We found five significant effects, involving students in health sciences, medicine and pharmacy, relating the number of sources of financial support to the four categories of career preference. No significant effects were found related to level of student loans debt. Our results suggest that financial support is a more strongly determining factor in career choices than the level of student loans debt. The four-category framework for student career preferences appears to be a useful model for further research.

  10. Cross-disciplinary management of polytrauma patients: radiological screening and comparison; Interdisziplinaeres Management von polytraumatisierten Patienten: Beitrag der Radiologie

    Energy Technology Data Exchange (ETDEWEB)

    Messmer, P. [Universitaetskliniken Basel, Dept. Chirurgie, Allgemeinchirurgische Klinik, Abt. Traumatologie (Switzerland); Loew, R.; Jacob, A.L. [Universitaetskliniken Basel, Dept. Medizinische Radiologie, Abt. Diagnostische Radiologie (Switzerland)

    2001-09-01

    The comprehensive survey addresses the various modalities available today for trauma screening and presents a comparative assessment of their value in respect of type of trauma and evidence provided. (orig./CB) [German] Die Versorgung polytraumatischer Patienten stellt hoechste Anforderungen an das Koennen des Radiologen. Neben einer schnellen und schonenden Durchfuehrung der notwendigen Diagnostik darf keine potenziell lebensbedrohende Verletzung uebersehen werden. Die Kriterien fuer eine rationelle Diagnostik wurden im ATLS-Kurs (Advanced Trauma Life Support) zusammengefasst. Es gilt, die sog. 'golden hour' moeglichst effektiv fuer die Primaerdiagnostik und -therapie zu nutzen. Haeufige Verletzungsformen beim Polytrauma sind das Schaedel-Hirn-Trauma, Thoraxverletzungen, Milzverletzungen, Leberverletzungen und Frakturen von Becken, Wirbelsaeule und Extremitaeten. Die Primaere und Sekundaere Radiologische Diagnostik ist abhaengig von der Ausstattung der Klinik und besteht aus einer abdominellen Sonographie, Thorax ap, Beckenuebersicht ap, Halswirbelsaeule seitlich sowie falls vorhanden aus CT und Angiographie. Ein definitiver Schritt zur Verkuerzung der Zeit bis zur Behandlung waeren sterile OP-Einheiten mit integrierter Roentgendiagnostik (moeglichst nativ und CT), die ein staendiges Umlagern und Transportieren des Patienten verhindern koennten. (orig.)

  11. Informing Food Protection Education: A Project to Define and Classify Resources for a Cross-Disciplinary Expert Community

    Science.gov (United States)

    Schenck-Hamlin, Donna; Pierquet, Jennifer; McClellan, Chuck

    2011-01-01

    In the wake of the September 2001 attacks, the U.S. government founded the Department of Homeland Security (DHS) with responsibility to develop a National Infrastructure Protection Plan for securing critical infrastructures and key resources. DHS established interdisciplinary networks of academic expertise administered through Centers of…

  12. Towards the understanding of the requirements of a communication language to support process interoperation in cross-disciplinary supply chains

    OpenAIRE

    DAS , BISHNU PADA; Young , R I M; Case , K; Rahimifard , S; Anumba , C; Bouchlaghem , N; Cutting Decelle , Anne-Francoise

    2007-01-01

    Abstract Many manufacturing organisations while doing business either directly or indirectly with other industrial sectors often encounter interoperability problems amongst software systems. This increases the business cost and reduces the efficiency. Research communities are exploring ways to reduce this cost. Incompatibility amongst the syntaxes and the semantics of the languages of application systems is the most common cause to this problem. The Process Specification Language (...

  13. From galaxy to universe? A cross-disciplinary review and analysis of public values publications from 1969 to 2012

    NARCIS (Netherlands)

    van der Wal, Z.; Nabatchi, T.; de Graaf, G.

    2015-01-01

    The study of public values (PVs) is generating growing interest in public administration and public management, yet many challenges and unanswered questions remain. For the study of PVs to progress, we need to go beyond the traditional boundaries of public administration and management, to explore

  14. Multiple approaches to understanding and preventing elder abuse: Introduction to the cross-disciplinary National Institutes of Health workshop.

    Science.gov (United States)

    Saylor, Katherine Witte

    2016-01-01

    On October 30, 2015, the National Institutes of Health (NIH) convened a workshop, "Multiple Approaches to Understanding and Preventing Elder Abuse," in Bethesda, Maryland. The workshop brought together experts from across disciplines to discuss research challenges, opportunities, and lessons learned from other fields. Participants included experts in elder abuse, child abuse, intimate partner violence (IPV), emergency medicine, and neuroscience. In this special issue of the Journal of Elder Abuse and Neglect, participants address topics explored before, during, and after the day-long workshop.

  15. Adopting Open-Source Software Applications in U. S. Higher Education: A Cross-Disciplinary Review of the Literature

    Science.gov (United States)

    van Rooij, Shahron Williams

    2009-01-01

    Higher Education institutions in the United States are considering Open Source software applications such as the Moodle and Sakai course management systems and the Kuali financial system to build integrated learning environments that serve both academic and administrative needs. Open Source is presumed to be more flexible and less costly than…

  16. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Fatigue life of metal treated by magnetic field

    Science.gov (United States)

    Liu, Zhao-Long; Hu, Hai-Yun; Fan, Tian-You; Xing, Xiu-San

    2009-03-01

    This paper investigates theoretically the influence of magnetization on fatigue life by using non-equilibrium statistical theory of fatigue fracture for metals. The fatigue microcrack growth rate is obtained from the dynamic equation of microcrack growth, where the influence of magnetization is described by an additional term in the potential energy of microcrack. The statistical value of fatigue life of metal under magnetic field is derived, which is expressed in terms of magnetic field and macrophysical as well as microphysical quantities. The fatigue life of AISI 4140 steel in static magnetic field from this theory is basically consistent with the experimental data.

  17. Assessing Cross-disciplinary Efficiency of Soil Amendments for Agro-biologically, Economically, and Ecologically Integrated Soil Health Management

    Science.gov (United States)

    2010-01-01

    Preventive and/or manipulative practices will be needed to maintain soil's biological, physiochemical, nutritional, and structural health in natural, managed, and disturbed ecosystems as a foundation for food security and global ecosystem sustainability. While there is a substantial body of interdisciplinary science on understanding function and structure of soil ecosystems, key gaps must be bridged in assessing integrated agro-biological, ecological, economical, and environmental efficiency of soil manipulation practices in time and space across ecosystems. This presentation discusses the application of a fertilizer use efficiency (FUE) model for assessing agronomic, economic, ecological, environmental, and nematode (pest) management efficiency of soil amendments. FUE is defined as increase in host productivity and/or decrease in plant-parasitic nematode population density in response to a given fertilizer treatment. Using the effects of nutrient amendment on Heterodera glycines population density and normalized difference vegetative index (indicator of physiological activities) of a soybean cultivar ‘CX 252’, how the FUE model recognizes variable responses and separates nutrient deficiency and toxicity from nematode parasitism as well as suitability of treatments designed to achieve desired biological and physiochemical soil health conditions is demonstrated. As part of bridging gaps between agricultural and ecological approaches to integrated understanding and management of soil health, modifications of the FUE model for analyzing the relationships amongst nematode community structure, soil parameters (eg. pH, nutrients, %OM), and plant response to soil amendment is discussed. PMID:22736840

  18. The Merapi Interactive Project: Offering a Fancy Cross-Disciplinary Scientific Understanding of Merapi Volcano to a Wide Audience.

    Science.gov (United States)

    Morin, J.; Kerlow, I.

    2015-12-01

    The Merapi volcano is of great interest to a wide audience as it is one of the most dangerous volcanoes worldwide and a beautiful touristic spot. The scientific literature available on that volcano both in Earth and Social sciences is rich but mostly inaccessible to the public because of the scientific jargon and the restricted database access. Merapi Interactive aims at developing clear information and attractive content about Merapi for a wide audience. The project is being produced by the Art and Media Group at the Earth Observatory of Singapore, and it takes the shape of an e-book. It offers a consistent, comprehensive, and jargon-filtered synthesis of the main volcanic-risk related topics about Merapi: volcanic mechanisms, eruptive history, associated hazards and risks, the way inhabitants and scientists deal with it, and what daily life at Merapi looks like. The project provides a background to better understand volcanoes, and it points out some interactions between scientists and society. We propose two levels of interpretation: one that is understandable by 10-year old kids and above and an expert level with deeper presentations of specific topics. Thus, the Merapi Interactive project intends to provide an engaging and comprehensive interactive book that should interest kids, adults, as well as Earth Sciences undergraduates and academics. Merapi Interactive is scheduled for delivery in mid-2016.

  19. Teaching a Cross-Disciplinary Environmental Science, Policy, and Culture Course on Costa Rica's Ecotourism to Business Students

    Science.gov (United States)

    Lester, Toni; Rodgers, Vikki L.

    2012-01-01

    Within the business world, there is growing evidence and increasing acceptance that sustainability and environmental practices are the main drivers for current innovation and success. We developed an interdisciplinary, offshore course where undergraduate business students could truly investigate and experience the benefits of environmentally and…

  20. Listening to Students: Building Bridges

    Science.gov (United States)

    Klein, Shira; Armillas-Tiseyra, Magali; Kuerbis, Alexis

    2011-01-01

    "Cross-disciplinary" has become a buzzword in academia. Here the authors offer a student-based perspective on the benefits of cross-disciplinary discussion, based on their experience in New York University's Graduate Forum. Founded ten years ago by Catharine Stimpson, then dean of the Graduate School of Arts and Science (GSAS), the forum…

  1. Efficient Annealing-Free P3HT:PC_6_1BM-Based Organic Solar Cells by Using a Novel Solvent Additive without a Halogen or Sulphur Atom

    International Nuclear Information System (INIS)

    Xiao Man-Jun; Zhu Wei-Guo; Shen Wen-Fei; Wang Jun-Yi; Han Liang-Liang; Chen Wei-Chao; Bao Xi-Chang; Yang Ren-Qiang

    2015-01-01

    The power conversion efficiency (PCE) of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PC_6_1BM) based organic solar cells (OSCs) is significantly improved by using benzyl acetate (BA), an organic compound without any halogen or sulphur atom, as a processing additive to control the blend morphology. The solar cells show PCE of 3.85% with a fill factor (FF) of 65.22%, which are higher than those of the common thermal annealing device (PCE 3.30%, FF 60.83%). The overall increased PCE depends upon the enhanced crystallinity of P3HT and good carriers transport, with a high balanced charge carrier mobility. (cross-disciplinary physics and related areas of science and technology)

  2. Development of risk-based nanomaterial groups for occupational exposure control

    International Nuclear Information System (INIS)

    Kuempel, E. D.; Castranova, V.; Geraci, C. L.; Schulte, P. A.

    2012-01-01

    Given the almost limitless variety of nanomaterials, it will be virtually impossible to assess the possible occupational health hazard of each nanomaterial individually. The development of science-based hazard and risk categories for nanomaterials is needed for decision-making about exposure control practices in the workplace. A possible strategy would be to select representative (benchmark) materials from various mode of action (MOA) classes, evaluate the hazard and develop risk estimates, and then apply a systematic comparison of new nanomaterials with the benchmark materials in the same MOA class. Poorly soluble particles are used here as an example to illustrate quantitative risk assessment methods for possible benchmark particles and occupational exposure control groups, given mode of action and relative toxicity. Linking such benchmark particles to specific exposure control bands would facilitate the translation of health hazard and quantitative risk information to the development of effective exposure control practices in the workplace. A key challenge is obtaining sufficient dose–response data, based on standard testing, to systematically evaluate the nanomaterials’ physical–chemical factors influencing their biological activity. Categorization processes involve both science-based analyses and default assumptions in the absence of substance-specific information. Utilizing data and information from related materials may facilitate initial determinations of exposure control systems for nanomaterials.

  3. Development of risk-based nanomaterial groups for occupational exposure control

    Science.gov (United States)

    Kuempel, E. D.; Castranova, V.; Geraci, C. L.; Schulte, P. A.

    2012-09-01

    Given the almost limitless variety of nanomaterials, it will be virtually impossible to assess the possible occupational health hazard of each nanomaterial individually. The development of science-based hazard and risk categories for nanomaterials is needed for decision-making about exposure control practices in the workplace. A possible strategy would be to select representative (benchmark) materials from various mode of action (MOA) classes, evaluate the hazard and develop risk estimates, and then apply a systematic comparison of new nanomaterials with the benchmark materials in the same MOA class. Poorly soluble particles are used here as an example to illustrate quantitative risk assessment methods for possible benchmark particles and occupational exposure control groups, given mode of action and relative toxicity. Linking such benchmark particles to specific exposure control bands would facilitate the translation of health hazard and quantitative risk information to the development of effective exposure control practices in the workplace. A key challenge is obtaining sufficient dose-response data, based on standard testing, to systematically evaluate the nanomaterials' physical-chemical factors influencing their biological activity. Categorization processes involve both science-based analyses and default assumptions in the absence of substance-specific information. Utilizing data and information from related materials may facilitate initial determinations of exposure control systems for nanomaterials.

  4. Cloud-Based Orchestration of a Model-Based Power and Data Analysis Toolchain

    Science.gov (United States)

    Post, Ethan; Cole, Bjorn; Dinkel, Kevin; Kim, Hongman; Lee, Erich; Nairouz, Bassem

    2016-01-01

    The proposed Europa Mission concept contains many engineering and scientific instruments that consume varying amounts of power and produce varying amounts of data throughout the mission. System-level power and data usage must be well understood and analyzed to verify design requirements. Numerous cross-disciplinary tools and analysis models are used to simulate the system-level spacecraft power and data behavior. This paper addresses the problem of orchestrating a consistent set of models, tools, and data in a unified analysis toolchain when ownership is distributed among numerous domain experts. An analysis and simulation environment was developed as a way to manage the complexity of the power and data analysis toolchain and to reduce the simulation turnaround time. A system model data repository is used as the trusted store of high-level inputs and results while other remote servers are used for archival of larger data sets and for analysis tool execution. Simulation data passes through numerous domain-specific analysis tools and end-to-end simulation execution is enabled through a web-based tool. The use of a cloud-based service facilitates coordination among distributed developers and enables scalable computation and storage needs, and ensures a consistent execution environment. Configuration management is emphasized to maintain traceability between current and historical simulation runs and their corresponding versions of models, tools and data.

  5. Engineering nanomaterials-based biosensors for food safety detection.

    Science.gov (United States)

    Lv, Man; Liu, Yang; Geng, Jinhui; Kou, Xiaohong; Xin, Zhihong; Yang, Dayong

    2018-05-30

    Food safety always remains a grand global challenge to human health, especially in developing countries. To solve food safety pertained problems, numerous strategies have been developed to detect biological and chemical contaminants in food. Among these approaches, nanomaterials-based biosensors provide opportunity to realize rapid, sensitive, efficient and portable detection, overcoming the restrictions and limitations of traditional methods such as complicated sample pretreatment, long detection time, and relying on expensive instruments and well-trained personnel. In this review article, we provide a cross-disciplinary perspective to review the progress of nanomaterials-based biosensors for the detection of food contaminants. The review article is organized by the category of food contaminants including pathogens/toxins, heavy metals, pesticides, veterinary drugs and illegal additives. In each category of food contaminant, the biosensing strategies are summarized including optical, colorimetric, fluorescent, electrochemical, and immune- biosensors; the relevant analytes, nanomaterials and biosensors are analyzed comprehensively. Future perspectives and challenges are also discussed briefly. We envision that our review could bridge the gap between the fields of food science and nanotechnology, providing implications for the scientists or engineers in both areas to collaborate and promote the development of nanomaterials-based biosensors for food safety detection. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Accelerating early anti-tuberculosis drug discovery by creating mycobacterial indicator strains that predict mode of action

    KAUST Repository

    Boot, Maikel; Commandeur, Susanna; Subudhi, Amit; Bahira, Meriem; Smith, Trever C.; Abdallah, Abdallah; van Gemert, Mae; Leliè vre, Joë l; Ballell, Lluí s; Aldridge, Bree B.; Pain, Arnab; Speer, Alexander; Bitter, Wilbert

    2018-01-01

    on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in M. marinum. We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct

  7. In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

    Science.gov (United States)

    Augustsson, Cecilia; Persson, Egon

    2014-11-13

    Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

  8. Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics.

    Science.gov (United States)

    Saitta, Kyle S; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R; Boelsterli, Urs A

    2014-01-01

    1.  We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2.  Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3.  Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4.  Using the fluorescent probe 5 (and 6)-carboxy-2',7'-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5.  These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones.

  9. Effect of Temperature and High Pressure on the Activity and Mode of Action of Fungal Pectin Methyl Esterase

    NARCIS (Netherlands)

    Duvetter, T.; Fraeye, I.; Sila, D.N.; Verlent, I.; Smout, C.; Clynen, E.; Schoofs, L.; Schols, H.A.; Hendrickx, M.; Loey, van A.

    2006-01-01

    Pectin was de-esterified with purified recombinant Aspergillus aculeatus pectin methyl esterase (PME) during isothermal-isobaric treatments. By measuring the release of methanol as a function of treatment time, the rate of enzymatic pectin conversion was determined. Elevated temperature and pressure

  10. Effect of temperature and high pressure on the activity and mode of action of fungal pectin methyl esterase.

    Science.gov (United States)

    Duvetter, Thomas; Fraeye, Ilse; Sila, Daniel N; Verlent, Isabel; Smout, Chantal; Clynen, Elke; Schoofs, Liliane; Schols, Henk; Hendrickx, Marc; Van Loey, Ann

    2006-01-01

    Pectin was de-esterified with purified recombinant Aspergillus aculeatus pectin methyl esterase (PME) during isothermal-isobaric treatments. By measuring the release of methanol as a function of treatment time, the rate of enzymatic pectin conversion was determined. Elevated temperature and pressure were found to stimulate PME activity. The highest rate of PME-catalyzed pectin de-esterification was obtained when combining pressures in the range 200-300 MPa with temperatures in the range 50-55 degrees C. The mode of pectin de-esterification was investigated by characterizing the pectin reaction products by enzymatic fingerprinting. No significant effect of increasing pressure (300 MPa) and/or temperature (50 degrees C) on the mode of pectin conversion was detected.

  11. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

    Directory of Open Access Journals (Sweden)

    Mallappa Kumara Swamy

    2016-01-01

    Full Text Available A wide range of medicinal and aromatic plants (MAPs have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes.

  12. An Overview of Mode of Action and Analytical Methods for Evaluation of Gas Phase Activities of Flame Retardants

    Directory of Open Access Journals (Sweden)

    Khalifah A. Salmeia

    2015-03-01

    Full Text Available The latest techniques used to prove, describe and analyze the gas phase activity of a fire retardant used in polymeric materials are briefly reviewed. Classical techniques, such as thermogravimetric analysis or microscale combustion calorimetry, as well as complex and advanced analytical techniques, such as modified microscale combustion calorimeter (MCC, molecular beam mass spectroscopy and vacuum ultra violet (VUV photoionization spectroscopy coupled with time of flight MS (TOF-MS, are described in this review. The recent advances in analytical techniques help not only in determining the gas phase activity of the flame-retardants but also identify possible reactive species responsible for gas phase flame inhibition. The complete understanding of the decomposition pathways and the flame retardant activity of a flame retardant system is essential for the development of new eco-friendly-tailored flame retardant molecules with high flame retardant efficiency.

  13. Modulation of Aromatase Activity as a Mode of Action for Endocrine Disrupting Chemicals in a Marine Fish

    Science.gov (United States)

    The steroidogenic enzyme aromatase catalyzes the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase....

  14. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  15. Cytotoxicity and mode of action of aeroplysinin-1 and a related dienone from the sponge Aplysina aerophoba

    NARCIS (Netherlands)

    Koulman, A; Proksch, P; Ebel, R; Beekman, AC; vanUden, W; Konings, AWT; Pedersen, JA; Pras, N; Woerdenbag, HJ

    Aeroplysinin-1 (1) and the structurally related dienone 2 were cytotoxic to Ehrlich ascites tumor (EAT) cells and HeLa tumor cells in the microculture tetrazolium (MTT) and clonogenic assays. Both compounds are bromotyrosine derivatives, isolated from the marine spong Aplysina aerophoba. As the

  16. Characterization and mode of action of two acetyl xylan esterases from Chrysosporium lucknowense C1 active towards acetylated xylans

    NARCIS (Netherlands)

    Pouvreau, L.A.M.; Jonathan, M.C.; Kabel, M.A.; Hinz, S.W.A.; Gruppen, H.; Schols, H.A.

    2011-01-01

    Two novel acetyl xylan esterases, Axe2 and Axe3, from Chrysosporium lucknowense (C1), belonging to the carbohydrate esterase families 5 and 1, respectively, were purified and biochemically characterized. Axe2 and Axe3 are able to hydrolyze acetyl groups both from simple acetylated

  17. Mode of action, origin and structure of the Paternal Sex Ratio chromosome in the parasitoid wasp Trichogramma kaykai

    NARCIS (Netherlands)

    Vugt, van J.J.F.A.

    2005-01-01

    Selfish genetic elements are defined as genetic elements that have a replication advantage relative to the rest of the genome. They are ubiquitous in nature and were extensively reported for almost all species studied so far. A special type of selfish genetic element, the sex ratio distorter, is

  18. Insight into the Mode of Action of Celangulin V on the Transmembrane Potential of Midgut Cells in Lepidopteran Larvae

    Directory of Open Access Journals (Sweden)

    Yingying Wang

    2017-12-01

    Full Text Available Celangulin V (CV is the main insecticidal constituent of Celastrus angulatus. The V-ATPase H subunit of the midgut cells of lepidopteran larvae is the putative target protein of CV. Here, we compared the effects of CV on the midgut membrane potentials of Mythimna separata and Agrotis ipsilon larvae with those of the Cry1Ab toxin from Bacillus thuringiensis and with those of inactive CV-MIA, a synthetic derivative of CV. We investigated the changes in the apical membrane potentials (Vam and basolateral membrane potentials (Vbm of the midguts of sixth-instar larvae force-fed with the test toxins. We also measured the Vam and Vbm of larval midguts that were directly incubated with the test toxins. Similar to the effect of Cry1Ab, the Vam of CV-treated midguts rapidly decayed over time in a dose-dependent manner. By contrast, CV-MIA did not influence Vam. Meanwhile, the Vam of A. ipsilon larval midguts directly incubated with CV decayed less than that of M. separata larval midguts, whereas that of larvae force-fed with CV did not significantly change. Similar to Cry1Ab, CV did not affect the Vbm of isolated midguts. CV significantly inhibited V-ATPase activity in a dose-dependent manner. Therefore, CV initially inhibits V-ATPase in the apical membrane and affects intracellular pH, homeostasis, and nutrient transport mechanisms in lepidopteran midgut cells.

  19. Metabolomic Analysis and Mode of Action of Metabolites of Tea Tree Oil Involved in the Suppression of Botrytis cinerea

    Directory of Open Access Journals (Sweden)

    Jiayu Xu

    2017-06-01

    Full Text Available Tea tree oil (TTO, a volatile essential oil, has been widely used as an antimicrobial agent. However, the mechanism underlying TTO antifungal activity is not fully understood. In this study, a comprehensive metabolomics survey was undertaken to identify changes in metabolite production in Botrytis cinerea cells treated with TTO. Significant differences in 91 metabolites were observed, including 8 upregulated and 83 downregulated metabolites in TTO-treated cells. The results indicate that TTO inhibits primary metabolic pathways through the suppression of the tricarboxylic acid (TCA cycle and fatty acid metabolism. Further experiments show that TTO treatment decreases the activities of key enzymes in the TCA cycle and increases the level of hydrogen peroxide (H2O2. Membrane damage is also induced by TTO treatment. We hypothesize that the effect of TTO on B. cinerea is achieved mainly by disruption of the TCA cycle and fatty acid metabolism, resulting in mitochondrial dysfunction and oxidative stress.

  20. Synthesis, Fungicidal Activity and Mode of Action of 4-Phenyl-6-trifluoromethyl-2-aminopyrimidines against Botrytis cinerea

    Directory of Open Access Journals (Sweden)

    Chunhui Liu

    2016-06-01

    Full Text Available Anilinopyrimidines are the main chemical agents for management of Botrytis cinerea. However, the drug resistance in fungi against this kind of compounds is very serious. To explore new potential fungicides against B. cinerea, a series of 4-phenyl-6-trifluoromethyl-2-amino-pyrimidine compounds (compounds III-1 to III-22 were synthesized, and their structures were confirmed by 1H-NMR, IR and MS. Most of these compounds possessed excellent fungicidal activity. The compounds III-3 and III-13 showed higher fungicidal activity than the positive control pyrimethanil on fructose gelatin agar (FGA, and compound III-3 on potato dextrose agar (PDA indicated high activity compared to the positive control cyprodinil. In vivo greenhouse results indicated that the activity of compounds III-3, III-8, and III-11 was significantly higher than that of the fungicide pyrimethanil. Scanning electron micrography (SEM and transmission electron micrography (TEM were applied to illustrate the mechanism of title compounds against B. cinerea. The title compounds, especially those containing a fluorine atom at the ortho-position on the benzene ring, could maintain the antifungal activity against B. cinerea, but their mechanism of action is different from that of cyprodinil. The present study lays a good foundation for us to find more efficient reagents against B. cinerea.

  1. Elicitors as alternative strategy to pesticides in grapevine? Current knowledge on their mode of action from controlled conditions to vineyard.

    Science.gov (United States)

    Delaunois, Bertrand; Farace, Giovanni; Jeandet, Philippe; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan; Cordelier, Sylvain

    2014-04-01

    Development and optimisation of alternative strategies to reduce the use of classic chemical inputs for protection against diseases in vineyard is becoming a necessity. Among these strategies, one of the most promising consists in the stimulation and/or potentiation of the grapevine defence responses by the means of elicitors. Elicitors are highly diverse molecules both in nature and origins. This review aims at providing an overview of the current knowledge on these molecules and will highlight their potential efficacy from the laboratory in controlled conditions to vineyards. Recent findings and concepts (especially on plant innate immunity) and the new terminology (microbe-associated molecular patterns, effectors, etc.) are also discussed in this context. Other objectives of this review are to highlight the difficulty of transferring elicitors use and results from the controlled conditions to the vineyard, to determine their practical and effective use in viticulture and to propose ideas for improving their efficacy in non-controlled conditions.

  2. Cross-tolerance in amphibians: wood frog mortality when exposed to three insecticides with a common mode of action.

    Science.gov (United States)

    Hua, Jessica; Cothran, Rickey; Stoler, Aaron; Relyea, Rick

    2013-04-01

    Insecticide tolerance and cross-tolerance in nontarget organisms is often overlooked despite its potential to buffer natural systems from anthropogenic influence. We exposed wood frog tadpoles from 15 populations to three acetylcholine esterase-inhibiting insecticides and found widespread variation in insecticide tolerance and evidence for cross-tolerance to these insecticides. Our results demonstrate that amphibian populations with tolerance to one pesticide may be tolerant to many other pesticides. Copyright © 2013 SETAC.

  3. Deciphering the mode of action of clinically relevant next generation c2 corrector compounds GLPG2737 and GLPG3221

    NARCIS (Netherlands)

    Peters, F.; Sahasrabudhe, P.; Gross-Wilde, H.; Kleizen, Bertrand; Conrath, K.; Braakman, I.

    2017-01-01

    The current therapeutic strategy to repair cystic fibrosis-causing defects in the chloride channel CFTR is to develop novel and better correctors (to improve folding) and potentiators (to improve function). Galapagos- AbbVie identified C2 correctors by high-throughput compound screening and Med Chem

  4. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Sotoca, A.M.; Vervoort, J.; Louisse, J.

    2013-01-01

    Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic

  5. Investigations into the chemistry, toxicology, metabolism and possible mode of action of O-ethyl S-methyl ethylphosphonothioate

    International Nuclear Information System (INIS)

    Hur, J.H.

    1989-01-01

    The chemical and metabolic oxidation of O-ethyl S-methyl ethylphosphonthioate (1) as a model compound was studied. This compound has the following toxicological properties: LD 50 (rat) 4.6 mg/kg, LD 50 (HF) 14.0 ug/g; k i (BAChE) = 303, k i (HFAChE) = 623. 13 C- and 31 P-NMR were mainly used in this study. The chemical oxidation of 1 with m-CPBA in CDCl 3 resulted in the formation of O-ethyl ethylphosphonic acid (2), O-ethyl ethylphosphinyloxymethylsulfonate (3) and O-ethyl ethylphosphonic acid anhydride (4). However, oxidation reaction of the model compound 1 with MPPA in D 2 O gave 2 and methylsulfonic acid. 1 was incubated in vitro with rat liver microsomal oxidase, and 2 and methylsulfenic acid were observed along with 1. For the in vivo study, a number of houseflies were treated with 14ug/g (LD 50 level) of 1. Analysis of the extracts of metabolic products provided evidence of the formation of 2. The existence of 1 S-oxide was demonstrated by use of a trapping method and the observation of oxidation products. The S-oxide has been proposed as a possible active intermediate responsible for the high toxicity of 1 to animals. However, owing to its instability it is unlikely that the S-oxide intermediate would persist in an aqueous biological environment long enough to attack the target enzyme. 4 was shown to have high toxicity to the rat and housefly and was also a potent anticholinesterase against BAChE and HFAChE . The presence of 4 was observed directly by the monitoring experiments during the chemical oxidation in aqueous conditions. This provided evidence that this metabolite is stable enough to attack the target site in biological systems. The anhydride 4 is proposed as the active metabolite in in vivo systems, responsible for high toxicity of 1

  6. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

    Science.gov (United States)

    2016-01-01

    A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes. PMID:28090211

  7. Piracetam: Its Possible Mode of Action in Children with Learning Disabilities and Its Effect on "in vitro" Cell Growth

    Science.gov (United States)

    Britz, R.; Bester, M. J.; da Silva, A.; Motsoane, N. A.; Marx, J.; Naude, H.; Pretorius, E.

    2006-01-01

    The use of pharmaceutical products such as Piracetam (Nootropil[R]) for the treatment of learning disabilities is becoming increasingly prevalent, and some studies have shown successful treatment of learning disabilities in children. This research article will discuss traditional uses of Piracetam, as well as uses in learning disabilities, with…

  8. Sensitivity and toxic mode of action of dietary organic and inorganic selenium in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Berntssen, M H G; Sundal, T K; Olsvik, P A; Amlund, H; Rasinger, J D; Sele, V; Hamre, K; Hillestad, M; Buttle, L; Ørnsrud, R

    2017-11-01

    Depending on its chemical form, selenium (Se) is a trace element with a narrow range between requirement and toxicity for most vertebrates. Traditional endpoints of Se toxicity include reduced growth, feed intake, and oxidative stress, while more recent finding describe disturbance in fatty acid synthesis as underlying toxic mechanism. To investigate overall metabolic mode of toxic action, with emphasis on lipid metabolism, a wide scope metabolomics pathway profiling was performed on Atlantic salmon (Salmo salar) (572±7g) that were fed organic and inorganic Se fortified diets. Atlantic salmon were fed a low natural background organic Se diet (0.35mg Se kg -1 , wet weight (WW)) fortified with inorganic sodium selenite or organic selenomethionine-yeast (SeMet-yeast) at two levels (∼1-2 or 15mgkg -1 , WW), in triplicate for 3 months. Apparent adverse effects were assessed by growth, feed intake, oxidative stress as production of thiobarbituric acid-reactive substances (TBARS) and levels of tocopherols, as well as an overall metabolomic pathway assessment. Fish fed 15mgkg -1 selenite, but not 15mgkg -1 SeMet-yeast, showed reduced feed intake, reduced growth, increased liver TBARS and reduced liver tocopherol. Main metabolic pathways significantly affected by 15mgkg -1 selenite, and to a lesser extent 15mgkg -1 SeMet-yeast, were lipid catabolism, endocannabinoids synthesis, and oxidant/glutathione metabolism. Disturbance in lipid metabolism was reflected by depressed levels of free fatty acids, monoacylglycerols and diacylglycerols as well as endocannabinoids. Specific for selenite was the significant reduction of metabolites in the S-Adenosylmethionine (SAM) pathway, indicating a use of methyl donors that could be allied with excess Se excretion. Dietary Se levels to respectively 1.1 and 2.1mgkg -1 selenite and SeMet-yeast did not affect any of the above mentioned parameters. Apparent toxic mechanisms at higher Se levels (15mgkg -1 ) included oxidative stress and altered lipid metabolism for both inorganic and organic Se, with higher toxicity for inorganic Se. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The mode of action of spatial repellents and their impact on vectorial capacity of Anopheles gambiae sensu stricto.

    Directory of Open Access Journals (Sweden)

    Sheila B Ogoma

    Full Text Available Malaria vector control relies on toxicity of insecticides used in long lasting insecticide treated nets and indoor residual spraying. This is despite evidence that sub-lethal insecticides reduce human-vector contact and malaria transmission. The impact of sub-lethal insecticides on host seeking and blood feeding of mosquitoes was measured. Taxis boxes distinguished between repellency and attraction inhibition of mosquitoes by measuring response of mosquitoes towards or away from Transfluthrin coils and humans. Protective effective distance of coils and long-term effects on blood feeding were measured in the semi-field tunnel and in a Peet Grady chamber. Laboratory reared pyrethroid susceptible Anopheles gambiae sensu stricto mosquitoes were used. In the taxis boxes, a higher proportion of mosquitoes (67%-82% were activated and flew towards the human in the presence of Transfluthrin coils. Coils did not hinder attraction of mosquitoes to the human. In the semi-field Tunnel, coils placed 0.3 m from the human reduced feeding by 86% (95% CI [0.66; 0.95] when used as a "bubble" compared to 65% (95% CI [0.51; 0.76] when used as a "point source". Mosquitoes exposed to coils inside a Peet Grady chamber were delayed from feeding normally for 12 hours but there was no effect on free flying and caged mosquitoes exposed in the semi-field tunnel. These findings indicate that airborne pyrethroids minimize human-vector contact through reduced and delayed blood feeding. This information is useful for the development of target product profiles of spatial repellent products that can be used to complement mainstream malaria vector control tools.

  10. 7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action

    Czech Academy of Sciences Publication Activity Database

    Perlíková, Pavla; Rylová, G.; Nauš, Petr; Elbert, Tomáš; Tloušťová, Eva; Bourderioux, Aurelie; Poštová Slavětínská, Lenka; Motyka, K.; Doležal, D.; Znojek, P.; Nová, A.; Harvanová, M.; Džubák, P.; Šiller, M.; Hlaváč, J.; Hajdúch, M.; Hocek, Michal

    2016-01-01

    Roč. 15, č. 5 (2016), s. 922-937 ISSN 1535-7163 R&D Projects: GA ČR GAP207/11/0344; GA TA ČR(CZ) TE01020028; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : sugar-modified derivatives * cross - coupling reactions * ribosomal RNA synthesis Subject RIV: CC - Organic Chemistry Impact factor: 5.764, year: 2016

  11. Nutrition and metabolism of parasitized and non-parasitized ruminants. Some approaches for studying the mode of action of parasites

    International Nuclear Information System (INIS)

    Leng, R.A.

    1981-01-01

    The effects of helminth infections on ruminant digestive function and metabolism are discussed against the background of current information on the mechanisms controlling feed intake and utilization in normal animals. Although parasites reduce productivity by impairing appetite and utilization of nutrients, few studies have been conducted on the function of the digestive tract and the metabolism of parasitized animals. Those areas which warrant further investigation are described, and the techniques which could be usefully applied are outlined. It is concluded that more emphasis should be given to the diet available to parasitized animals, and that by using diets of different digestibility and protein content, valuable information could be obtained as to the relative importance of reduced appetite and reduced efficiency of feed utilization. Central to all studies is a proper delineation of the fate of proteins in the small intestine of parasitized animals, and characterization of the types of bacteria in the gut and their effects on endogenous protein losses. The application of 15 N is mentioned. The potential usefulness of 14 C (eg. to measure the flow of digesta, to the lower digestive tract; clearance of 14 C-propionate from blood; etc.) is described

  12. Haloxyfop mode of action in liquid cultures of proso millet: An analysis of haloxyfop sensitivity changes during growth

    International Nuclear Information System (INIS)

    Irzyk, G.P.

    1989-01-01

    Haloxyfop is a grass-selective herbicide that inhibits acetyl-CoA carboxylase in species that are not tolerant to the herbicide. Liquid cultures of proso millet (Panicum miliaceum) cells treated with haloxyfop at different phases of growth exhibited different levels of sensitivity to the herbicide. Treatment of 1-d cultures with 1 μM haloxyfop completely inhibited growth within 48 h. In contrast, 1 mM haloxyfop was required to elicit a similar response in 4-, 7-, or 10-d cultures. Calculated IC 50 values indicated a 300-fold decrease in haloxyfop sensitivity during the period from 1 to 4 d. This period of growth coincided with the greatest increase in cell number during culture growth and suggested that dividing cells are most sensitive to haloxyfop. Uptake and metabolism of 14 C-haloxyfop in 1-d and 4-d cultures were compared. In both cultures, amounts of radiolabel uptake were similar. Almost all radioactivity extracted from 1- and 4-d cells was present as the parent compound. These results suggested that the sensitivity change was related to other factors. Acetyl-CoA carboxylase activity of proso millet cells, measured in vitro by the acetyl-CoA-dependent incorporation of 14 C-bicarbonate into an acid-stable product, was essentially constant during culture growth. Micromolar concentrations of haloxyfop significantly inhibited acetyl-CoA carboxylase activity from both sensitive and insensitive cultures. Thus, the change in the sensitivity of cultures to haloxyfop was not correlated with changes in acetyl-CoA carboxylase abundance, activity, or sensitivity to haloxyfop during culture growth. In vivo incorporation of 14 C-acetate into lipids was decreased by 1 μM haloxyfop in both 1-d and 4-d cultures at the earliest sampling times but the amount of inhibition was significantly greater in the sensitive cultures

  13. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

    Science.gov (United States)

    Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

    2009-12-01

    Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

  14. Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment

    Directory of Open Access Journals (Sweden)

    Asher Ornoy

    2010-01-01

    Full Text Available Offspring of mothers using ethanol during pregnancy are known to suffer from developmental delays and/or a variety of behavioral changes. Ethanol, may affect the developing fetus in a dose dependent manner. With very high repetitive doses there is a 6–10% chance of the fetus developing the fetal alcoholic syndrome manifested by prenatal and postnatal growth deficiency, specific craniofacial dysmorphic features, mental retardation, behavioral changes and a variety of major anomalies. With lower repetitive doses there is a risk of "alcoholic effects" mainly manifested by slight intellectual impairment, growth disturbances and behavioral changes. Binge drinking may impose some danger of slight intellectual deficiency. It is advised to offer maternal abstinence programs prior to pregnancy, but they may also be initiated during pregnancy with accompanying close medical care. The long term intellectual outcome of children born to ethanol dependent mothers is influenced to a large extent by the environment in which the exposed child is raised.

  15. A Novel High-Molecular-Mass Bacteriocin Produced by Enterococcus faecium: Biochemical Features and Mode of Action.

    Science.gov (United States)

    Vasilchenko, A S; Vasilchenko, A V; Valyshev, A V; Rogozhin, E A

    2018-02-08

    Discovery of a novel bacteriocin is always an event in sciences, since cultivation of most bacterial species is a general problem in microbiology. This statement is reflected by the fact that number of bacteriocins is smaller for tenfold comparing to known antimicrobial peptides. We cultivated Enterococcus faecium on simplified medium to reduce amount of purification steps. This approach allows to purify the novel heavy weight bacteriocin produced by E. faecium ICIS 7. The novelty of this bacteriocin, named enterocin-7, was confirmed by N-terminal sequencing and by comparing the structural-functional properties with available data. Purified enterocin-7 is characterized by a sequence of amino acid residues having no homology in UniProt/SwissProt/TrEMBL databases: NH2 - Asp - Ala - His - Leu - Ser - Glu - Val - Ala - Glu - Arg - Phe - Glu - Asp - Leu - Gly. Isolated thermostable protein has a molecular mass of 65 kDa, which allows it to be classified into class III in bacteriocin classification schemes. Enterocin-7 displayed a broad spectrum of activity against some Gram-positive and Gram-negative microorganisms. Fluorescent microscopy and spectroscopy showed the permeabilizing mechanism of the action of enterocin-7, which is realized within a few minutes.

  16. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites : Environmental Science and Pollution Research

    NARCIS (Netherlands)

    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

    Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming.

  17. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites : Environmental Science and Pollution Research

    OpenAIRE

    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.

    2015-01-01

    Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicoti...

  18. The mode of action of spatial repellents and their impact on vectorial capacity of Anopheles gambiae sensu stricto.

    Science.gov (United States)

    Ogoma, Sheila B; Ngonyani, Hassan; Simfukwe, Emmanuel T; Mseka, Antony; Moore, Jason; Maia, Marta F; Moore, Sarah J; Lorenz, Lena M

    2014-01-01

    Malaria vector control relies on toxicity of insecticides used in long lasting insecticide treated nets and indoor residual spraying. This is despite evidence that sub-lethal insecticides reduce human-vector contact and malaria transmission. The impact of sub-lethal insecticides on host seeking and blood feeding of mosquitoes was measured. Taxis boxes distinguished between repellency and attraction inhibition of mosquitoes by measuring response of mosquitoes towards or away from Transfluthrin coils and humans. Protective effective distance of coils and long-term effects on blood feeding were measured in the semi-field tunnel and in a Peet Grady chamber. Laboratory reared pyrethroid susceptible Anopheles gambiae sensu stricto mosquitoes were used. In the taxis boxes, a higher proportion of mosquitoes (67%-82%) were activated and flew towards the human in the presence of Transfluthrin coils. Coils did not hinder attraction of mosquitoes to the human. In the semi-field Tunnel, coils placed 0.3 m from the human reduced feeding by 86% (95% CI [0.66; 0.95]) when used as a "bubble" compared to 65% (95% CI [0.51; 0.76]) when used as a "point source". Mosquitoes exposed to coils inside a Peet Grady chamber were delayed from feeding normally for 12 hours but there was no effect on free flying and caged mosquitoes exposed in the semi-field tunnel. These findings indicate that airborne pyrethroids minimize human-vector contact through reduced and delayed blood feeding. This information is useful for the development of target product profiles of spatial repellent products that can be used to complement mainstream malaria vector control tools.

  19. Modes of Action and Functions of ERECTA-family Receptor-like Kinases in Plant Organ Growth and Development

    Energy Technology Data Exchange (ETDEWEB)

    TORII, Keiko U.

    2012-05-01

    Higher plants constitute the central resource for renewable lignocellulose biomass that can supplement for the world's depleting stores of fossil fuels. As such, understanding the molecular and genetic mechanisms of plant organ growth will provide key knowledge and genetic resources that enables manipulation of plant biomass feedstock for better growth and productivity. The goal of this proposal is to understand how cell proliferation and growth are coordinated during aboveground organ morphogenesis, and how cell-cell signaling mediated by a family of receptor kinases coordinates plant organogenesis. The well-established model plant Arabidopsis thaliana is used for our research to facilitate rapid progress. Specifically, we focus on how ERECTA-family leucine-rich repeat receptor kinases (LRR-RLKs) interact in a synergistic manner to promote organogenesis and pattern formation in Arabidopsis. This project was highly successful, resulted in fourteen publications including nine peer-reviewed original research articles. One provisional US patent has been filed through this DOE funding. We have addressed the critical roles for a family of receptor kinases in coordinating proliferation and differentiation of plants, and we successfully elucidated the downstream targets of this signaling pathway in specifying stomatal patterning.

  20. 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

    Directory of Open Access Journals (Sweden)

    Myrna J. Simpson

    2013-08-01

    Full Text Available 1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS, betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA of contaminants is not clearly defined.